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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 307 records · Page 17Linked to original sources
PubMed1985

Chemotactic activity of plasma and lung lymph in sheep with endotoxemia: effect of hydroxyl radical scavengers.

The formation and release of circulating chemoattractants has been considered to be responsible for the initial pulmonary leukostasis and subsequent pulmonary vascular injury seen with endotoxemia. Oxygen radicals released from granulocytes can produce these factors. Our purpose was (1) to determine whether chemotaxins are released with endotoxemia and whether the lung is the source of these factors and (2) if there is a cause and effect relationship between the release of chemoattractants and the lung injury. Lung lymph flow, QL, lymph protein clearance, and vascular pressures were used to monitor lung vascular integrity. Escherichia coli endotoxin was infused into 12 sheep. Six sheep were pretreated with dimethyl thiourea (DMTU), a scavenger of hydroxide ion radicals. Chemotactic activity (CA) of plasma and lung lymph was determined during baseline, the pulmonary hypertensive phase, and the permeability phase of the lung injury. It was found that endotoxemia was associated with generation of a granulocyte chemotactic factor in plasma but not in lung lymph. The peak increase in plasma CA occurred after the early pulmonary leukostasis. Pretreatment with DMTU eliminated the increased CA but had no effect on the initial leukopenia or the lung injury. It was concluded that (1) the lung is not the major source of increased CA after endotoxin and (2) increased plasma CA occurs but does not appear to be causative of the initial pulmonary leukostasis or the granulocyte-induced lung injury.

Animals↗
PubMed1985

Effect of a body burn on the lung response to endotoxin.

Our purpose was, in general, to determine the effect of a body burn on the pulmonary response to endotoxemia and, specifically, to determine whether increased thromboxane (TxA2) production by the burn wound was responsible for the accentuated lung injury. Thirty-two unanesthetized sheep with lung and soft tissue lymph fistulae were studied. Twelve sheep were given a sublethal dose of intravenous E. coli endotoxin (2 micrograms/kg). A characteristic two-phase injury was noted as evidenced by early pulmonary hypertension and hypoxia and later increased lung permeability. TxA2 was significantly increased in lung lymph as well as aortic plasma relative to venous plasma, indicating the lung to be the source. Twelve of 12 sheep survived. Five of 13 sheep died from endotoxemia when given 3-5 days after a 25% total body surface (TBS) burn and five of seven died with endotoxin (2 micrograms/kg) and a 50% burn. Physiologic parameters were at preburn levels before endotoxin. Animals died both during the early phase from hypoxia and the later phase due, in large part, to increasing pulmonary dysfunction. Absolute levels of TxA2 were not increased in the postburn animals, nor was there a clear release of TxA2 from burn tissue to explain the accentuated response. Prostacyclin levels were, however, less elevated in postburn animals in response to endotoxin, thereby altering the TxA2/PGI2 ratio in favor of TxA2. However, a cause and effect relationship between the increased lung injury and TxA2 remains undetermined. Lymph flow or lymph protein content was not altered in burn tissue in response to endotoxin.

Animals↗
PubMed1985

Ring chromosome 21: characterization of DNA sequences at sites of breakage and reunion.

We have presented studies of an unusual child with an r21 chromosome who lacks the phenotype of Down syndrome. We have sequenced the region of the breakpoint in the normal DNA fragment and have isolated the abnormal breakpoint fragment as a 7.5-kb EcoRI fragment. We have preliminary evidence localizing the breakpoint to a few hundred base pairs of 21q DNA. Since the child lacks the classical phenotype of Down syndrome, further studies of the DNA distal to the breakpoint on the long arm of chromosome 21 may help us to elucidate "genes" important to the phenotype of Down syndrome.

Base Sequence↗
PubMed1985

Differential ability of a T-antigen transport-defective mutant of simian virus 40 to transform primary and established rodent cells.

The transforming potential and oncogenicity of a simian virus 40 (SV40) mutant affecting T-antigen (T-ag), SV40(cT)-3, was examined in an effort to dissect T-ag functions in transformation. SV40(cT)-3 has a point mutation at nucleotide 4434 that abolishes the transport of T-ag to the nucleus but does not affect its association with the cell surface. Transfection-transformation assays were performed with primary cells and established cell lines of mouse and rat origin. The efficiency of transformation for established cell lines by SV40(cT)-3 was comparable to that of wild-type SV40, indicating that transformation of established cell lines can occur in the absence of detectable amounts of nuclear T-ag. Transformation of primary mouse embryo fibroblasts by SV40(cT)-3 was markedly influenced by culture conditions; the relative transforming frequency was dramatically reduced in assays involving focus formation in low serum concentrations or anchorage-independent growth. Immunofluorescence tests revealed that the transformed mouse embryo fibroblasts partially transport the mutant cT-ag to the cell nucleus. Transformed cell lines induced by SV40(cT)-3 did not differ in growth properties from wild-type transformants. SV40(cT)-3 was completely defective for the transformation of primary baby rat kidney cells, a primary cell type unable to transport the mutant T-ag to the nucleus. The intracellular localization of cellular protein p53 was found to mimic T-ag distribution in all the transformants analyzed. The mutant virus was weakly oncogenic in vivo: the induction of tumors in newborn hamsters by SV40(cT)-3 was reduced in incidence and delayed in appearance in comparison to wild-type SV40. These observations suggest that cellular transformation is regulated by both nuclear and surface-associated forms of SV40 T-ag.

Animals↗
PubMed1985

Popliteal cysts and deep venous thrombosis: Tc-99m red blood cell venography.

Thirty-four patients who clinically were suspected of having deep venous thrombosis (DVT) underwent Tc-99m red blood cell (RBC) venography followed by contrast venography. The sensitivity (88%) and specificity (94%) of Tc-99m RBC venography for DVT confirmed findings of previous studies. Twenty-four patients who had proved popliteal cysts and swollen calves also were examined using Tc-99m RBC venography. Large cysts (greater than 9 X 4 X 4 cm) showed lack of DVT features, photon deficient cold areas in the popliteal fossa, and diversion of venous flow around the photon deficient area. These features were seen in 25% of the study population (six patients), and assisted in the distinction between the two conditions.

Adult↗
PubMed1985

Relationship of increased lung serotonin levels to endotoxin-induced pulmonary hypertension in sheep. Effect of a serotonin antagonist.

A persistent pulmonary artery hypertension, increased airways resistance, increased vascular permeability to protein, and hypoxia are characteristic of sepsis-induced ARDS in humans and are present in the late phase injury response seen in sheep after endotoxin. Our purpose was to determine the role of serotonin, 5-HT, in the steady-state pulmonary hypertension and decreased arterial oxygen tension seen beginning approximately 3 h after Escherichia coli endotoxin injury (2 micrograms/kg) in the adult sheep. Plasma 5-HT levels remained constant, whereas lung lymph values increased from a baseline of 60 +/- 40 to 180 +/- 70 and 270 +/- 90 ng/ml at 1-h and at 3- to 5-h periods, respectively, after endotoxin. Platelet count decreased significantly only at the 3-h time period. Ketanserin, a 5-HT antagonist, was infused (0.15 mg/kg/h) in 7 sheep during endotoxin injury. The degree of early pulmonary hypertension and hypoxia was not affected by ketanserin. Mean values for pulmonary artery pressure and arterial oxygen tension were 40 +/- 8 mmHg and 70 +/- 8 torr for endotoxin alone and 38 +/- 7 mmHg and 72 +/- 7 torr for the ketanserin group. Steady-state, protein-rich pulmonary perfusion was also not altered, being increased 3-fold in both groups. Pulmonary hypertension and hypoxia were significantly attenuated, however, at the 3- to 5-h period with ketanserin, compared with endotoxin alone, the pulmonary artery pressure decreasing from 29 +/- 5 to 22 +/- 4 mmHg and the PaO2 increasing from 75 +/- 4 to 83 +/- 5 torr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Early lung dysfunction after major burns: role of edema and vasoactive mediators.

We determined the effect of a body burn on pulmonary function. Full-thickness burns varying in size from 25 to 70% of total body surface (TBS), were produced in sheep. Resuscitation was performed with lactated Ringer's. We noted an increase in lung transvascular fluid flux as measured by lymph flow, Q1, during the resuscitation period, varying from one- to threefold over baseline with the degree of increase directly proportional to the burn size. The increase in QL could be totally explained by the degree of hypoproteinemia which was also proportional to burn size. Transient pulmonary hypertension 20 +/- 4 to 26 +/- 5 mm Hg and a decrease in PaO2 from 90 +/- 5 to 83 +/- 6 torr occurred in the 50 and 70% burns as well as a significant decrease in lung compliance. These alterations were not due to pulmonary edema as there was no increase in measured lung water. Also, the increase in QL could be prevented by using a combination of Dextran and protein for resuscitation but this had no effect on the hypertension or hypoxia. Burn lymph and venous plasma thromboxane levels were increased during this period of lung dysfunction. Ibuprofen 12.5 mg/kg preburn and 12.5 mg/kg every 2 hours postburn decreased the degree of dysfunction suggesting a cause and effect relationship.

Animals↗
PubMed1985

Effect of hydroxyl radical scavenging on endotoxin-induced lung injury.

The release of oxygen radicals, in particular the hydroxyl radical, from sequestered neutrophils produces acute lung injury after a number of insults. Our purpose was to determine whether hydroxyl radical, OH., is responsible for the lung injury from endotoxin characterized by (1) pulmonary leukostasis, (2) increased thromboxane production leading to pulmonary hypertension and hypoxia, and (3) increased protein permeability. This hypothesis was tested by infusion of a selective OH. scavenger, dimethyl thiourea (0.75 gm/kg), into unanesthetized sheep before endotoxin and comparison of the response to that seen with endotoxin alone. Pulmonary vascular integrity was measured by the use of lung lymph flow, QL, and lymph protein transport. Thromboxane A2 was measured as TxB2 and prostacyclin as 6-keto-PGF1 alpha. We found no difference in the degree of leukopenia and hypoxia after endotoxin or the levels of TxB2, 6-keto-PGF1 alpha, and pulmonary hypertension with dimethyl thiourea, compared with endotoxin alone. The permeability injury was also identical, with a twofold to threefold increase in protein-rich lymph seen in both groups. It appears that OH. does not play a major causative role in either phase of endotoxin lung injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Role of subcutaneous tissue endotoxin in the production of prostanoid-induced lung injury: comparison with intravenous endotoxin response.

Local injection of endotoxin into soft tissues of the flank results in hypoxia and pulmonary hypertension. Our purpose was to determine whether this was caused by tissue prostanoid production or production by the lung as is seen with endotoxemia. Twenty-six sheep were prepared with lung and flank tissue lymph fistulae. Thirteen sheep were given 2 micrograms/kg Escherichia coli endotoxin into the flank soft tissue, six of which were pretreated with ibuprofen, 12.5 mg/kg. Thirteen sheep were given intravenous endotoxin, 2 micrograms/kg, with six pretreated with ibuprofen. An early hypertensive phase was noted with both insults characterized by pulmonary hypertension, hypoxia, and increased lung lymph flow (QL). With subcutaneous tissue endotoxin, there was a significant increase in tissue lymph TxB2 and 6-keto-PGF1 alpha when compared to lung lymph and increased values in venous plasma compared to arterial plasma, indicating tissue to be the source. With intravenous endotoxin, lung lymph and aortic plasma levels were significantly higher than tissue lymph and venous plasma, respectively. The hypoxia, hypertension and increased prostanoids were prevented using ibuprofen. An increased lung permeability phase was noted with intravenous endotoxin but not with tissue endotoxin. As expected, this phase was not inhibited with ibuprofen and, therefore, not prostanoid-induced.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Role of oxygen radicals in endotoxin-induced lung injury.

We tested the hypothesis that the increased permeability in the pulmonary microcirculation seen with endotoxin is caused by the release of oxygen radicals from activated neutrophils. We first compared the pulmonary injury in sheep caused by low-dose endotoxin with that produced by phorbol myristate acetate, an agent that selectively causes the release of oxygen radicals from neutrophils. We then determined the degree of lung tissue lipid peroxidation, a reflection of direct oxygen radical damage after endotoxin and phorbol myristate acetate. Both agents produced a nearly identical increase in protein permeability; however, peroxidation was only evident with phorbol myristate acetate. Higher doses of endotoxin did result in increased lung peroxidation as well as a more severe physiologic injury. We can conclude that oxygen radical release, most likely from neutrophils, occurs with endotoxin. However, the permeability injury may not be the direct result of increased lipid peroxidation, as increased permeability can be seen without measurable increases in this parameter.

Animals↗
PubMed1984

Transformation of mouse mammary epithelial cells by papovavirus SV40.

Primary and established murine mammary epithelial cells and wild-type SV40 were employed to study the phenomenon of epithelial cell transformation. Thirteen independent transformed cell lines were derived. All contained SV40 intranuclear T antigen. Eight transformed mammary cell lines were examined ultrastructurally and all were found to exhibit pronounced epithelial cell characteristics, including desmosomes and tight junctions. Growth studies revealed that while normal mammary cells were unable to grow in low serum (2% FBS), established Cl S1 mammary cells and SV40-transformed mammary epithelial cells replicated well. Cell densities achieved by the transformants were only slightly elevated in high serum (13% FBS) over normal cell values. All the transformants formed colonies on plastic and exhibited anchorage-independent growth in methylcellulose. Five of the transformed lines were tumorigenic in syngeneic animals, in marked contrast to the lack of transplantability usually observed with SV40-transformed mouse fibroblasts. Anchorage-independent growth was not a predictor of tumorigenic potential in this system. The transformants exhibited a spectrum of responsiveness to exogenous growth factors. This study establishes that the SV40-murine mammary cell system is a valid model for analyses of the process and consequences of epithelial cell transformation, in general, and mammary cell transformation in particular.

Animals↗
PubMed1984

Serum total immunoglobulin E levels in Canadian adults.

A history of respiratory and allergic disorders was obtained in a white, rural population with ages 20 to 65 yr. Allergy skin testing was performed, and total IgE was measured by PRIST method. One thousand eight hundred and fourteen subjects were studied. Those subjects with positive allergic skin reactions and a history of allergic disorders and smoking were excluded to provide a reference group to derive "normal" values of total IgE. The mean level of the total IgE of this reference group was 12.1 U/ml. The upper limit of the normal range of total IgE levels was estimated at 87.3 U/ml. IgE levels did not differ between the sexes or with age in our adult population.

Adult↗
PubMed1984

Modulation of the immune response by gangliosides. Inhibition of adherent monocyte accessory function in vitro.

Gangliosides are potent inhibitors of lymphoproliferative responses. Selectively greater inhibitory effects of gangliosides on antigen-induced (vs. mitogen-induced) proliferation have been documented; e.g., 50 nmol of highly purified bovine brain gangliosides (BBG)/ml caused greater than or equal to 87% inhibition of proliferative responses of human peripheral blood mononuclear cells (PBMC) to three soluble specific antigens (Candida, streptokinase-streptodornase, and tetanus toxoid) vs. less than or equal to 37% inhibition of responses to three nonspecific mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen). The possibility that BBG interfere with adherent monocyte accessory function, upon which responses to soluble specific antigens are strictly dependent, was therefore considered. PBMC were separated into the adherent and nonadherent subpopulations, exposed to BBG, recombined, and their proliferative responses were measured. Unseparated PBMC preincubated for 48-72 h with 100 nmol BBG/ml and then washed to remove unbound BBG exhibited 73-76% inhibition of subsequent antigen-induced lymphoproliferation. Separate pretreatment of both adherent and nonadherent cell subpopulations in BBG under the same conditions resulted in similar (72-82%) inhibition, which was reproduced by preincubation of only the adherent cells in BBG. Preincubation of only the nonadherent cells in BBG was not inhibitory. Inhibition (a) was independent of whether gangliosides were added in solution or incorporated into liposomes, (b) was abrogated by adding untreated monocytes to cultures containing adherent cells that were preexposed to BBG (excluding the possibility that BBG was inducing suppression mediated by adherent cells), and (c) was reversible by further incubation of BBG-pretreated adherent cells in control medium. Together, these results delineate a mechanism by which gangliosides modulate lymphoproliferative responses--direct, noncytotoxic, and ultimately reversible inhibition of the accessory function of adherent monocytes.

Animals↗
PubMed1984

Effect of hemorrhagic shock on endotoxin-induced pulmonary hypertension and increased vascular permeability in unanesthetized sheep.

The lung is very susceptible to sepsis or endotoxin injury in the trauma patient. We studied the effect of an episode of hemorrhagic shock and resuscitation on the prostaglandin-induced pulmonary hypertension and leukocyte-induced increased permeability phase of endotoxin lung injury. Eight unanesthetized sheep with chronic lung lymph fistula were bled 50% of blood volume for 2 hr, then resuscitated. Thromboxane, TxA2, levels increased from 0.1 to 0.6 ng/ml during shock, while blood white cell count decreased. Both parameters returned to baseline while lung lymph flow increased twofold during resuscitation with lymph being protein-poor, indicating no increase in permeability. Lung water was not increased but some pulmonary leukostasis was evident histologically after resuscitation. We then studied the effect of this process on all immediate endotoxin insult. Seven unanesthetized sheep were given 0.7 microgram/kg E. coli endotoxin alone, and again after shock and resuscitation, in paired studies performed 3 days apart. There was no difference in either the early pulmonary hypertension or the later increased permeability phase of endotoxin lung injury when comparing the paired studies, as measured by lymph flow and protein flux. Hemorrhagic shock, despite producing a transient increase in thromboxane and pulmonary leukocyte sequestration, does not accentuate the lung injury of endotoxin if the shock state is adequately resuscitated.

Animals↗
PubMed1984

Effect of endotoxin on the integrity of the peripheral (soft tissue) microcirculation.

Peripheral edema, hypoproteinemia, and increased fluid requirements are characteristically seen with sepsis. Our purpose was to determine whether the soft tissue edema is caused by a direct vascular injury from sepsis or is secondary to hypoproteinemia. We determined the effect of endotoxin on peripheral (soft tissue) microvascular integrity using lymph flow (QL) and lymph/plasma (L/P) protein ratio to reflect fluid flux and increased permeability. Response was compared with that seen in the lung. Fourteen unanesthetized sheep were given intravenous E. coli endotoxin 2 micrograms/kg. Vascular pressures and cardiac output (CO) were maintained constant with the necessary fluid infusion. Lung QL increased two- to fourfold in all animals with lymph being protein-rich, indicating increased permeability. Peripheral QL increased transiently in response to an initial increase in vascular pressure returning rapidly to baseline except in those animals (N = 5) demonstrating hypoproteinemia where QL remained increased by 50 to 75%. The increased QL was totally explained by the degree of protein depletion, with no evidence of increased permeability. To assure an adequate endotoxin exposure to the peripheral microvessels, endotoxin (2 micrograms/kg) was also directly injected into the tissue drained by the soft tissue lymphatic. We noted a characteristic endotoxin pulmonary hypertension phase but, again, no increase in peripheral microvascular permeability was found. We conclude that endotoxemia does not alter peripheral microvascular permeability if tissue perfusion is maintained, while the lung is clearly a target organ. Hypoproteinemia may be responsible for the early edema in soft tissues with sepsis.

Animals↗