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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 289 records · Page 16Linked to original sources
PubMed1986

Studies on precellular evolution: the encapsulation of polyribonucleotides by liposomes.

Liposomes are 5 to 50 micron vesicles with an internal aqueous environment, whose amphiphilic lipidic components self-assemble into systems with at least one double-layered membrane. Liposomes have been suggested as possible models of precellular systems formed in the early Archean Earth from lipids of non-enzymatic origin. Since it is generally accepted that RNA molecules preceded double-stranded DNA molecules as genetic material, we have studied the encapsulation of polyribonucleotides within liposomes made from dipalmitoyl phosphatidylcholine, and from egg yolk phosphatidylcholine to which cholesterol was added in some cases. The liposomes were prepared under anoxic conditions following the reverse phase evaporation method described by Szoka and Papahadjopoulos. Quantitative determinations show that approximately 50% of the available lipids form liposomes, and that up to 5% of the polyribonucleotides can be entrapped by them. We have also studied the encapsulation of polyribonucleotides in the presence of 1) urea and cyanamide, two non-electrolytes that have been used as prebiotic condensing agents, and 2) of Zn++ and Pb++, two cations employed in the non-enzymatic template-directed synthesis of polyribonucleotides from activated nucleotides.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1986

On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups.

Seven beta-thalassemia genes were characterized after they were identified as candidates for previously undescribed mutations based upon the close association of DNA polymorphism haplotypes in the beta-globin gene cluster with specific ethnic mutations. The molecular defect in four of these genes was identical, a frameshift deletion of four nucleotides (-CTTT) within codons 41 and 42. This gene represents a common Southeast Asian mutation shared by a Laotian beta-thalassemia gene, [framework 1 (FR1)], a Vietnamese (FR1), and two Chinese patients (FR3 Asian and FR1). The deletion has been observed previously in Chinese (FR1) and Asian Indians (FR2) and is an example of independent origins of the same molecular defect, possible interallelic gene conversion (as it is seen on two different beta-globin gene frameworks in Chinese), and mutant gene migration in the Asian countries. A second example of mutant gene migration was identified in an Iranian patient with a nucleotide insertion (G) between codons 8 and 9, the same mutation previously found in an Asian Indian in the same chromosomal background. The last two genes examined represent further strong evidence for independent origins of mutation. A C-to-T substitution at position -88 in an Asian Indian has been identified previously in an American Black on a different beta-globin gene framework, and a G-to-A transition at nucleotide 1 of intervening sequence 2 found in an American Black has been observed previously on a different chromosome background in Mediterraneans. This study suggests that there are not many common beta-thalassemia mutations remaining to be discovered. It also suggests that certain sequences in the beta-globin gene are relatively mutation sensitive.

Black People↗
PubMed1986

Fluctuation of simian virus 40 (SV40) super T-antigen expression in tumors induced by SV40-transformed mouse mammary epithelial cells.

Higher-molecular-weight forms of the simian virus 40 (SV40) large tumor antigen (T-Ag), designated super T-Ag, are commonly found in SV40-transformed rodent cells. We examined the potential role of super T-Ag in neoplastic progression by using a series of clonal SV40-transformed mouse mammary epithelial cell lines. We confirmed an association between the presence of super T-Ag and cellular anchorage-independent growth in methylcellulose. However, tumorigenicity in nude mice did not correlate with the expression of super T-Ag. In the tumors that developed in nude mice, super T-Ag expression fluctuated almost randomly. Cell surface iodination showed that super T-Ag molecules were transported to the epithelial cell surface. The biological functions of super T-Ag remain obscure, but it is clear that it is not important for tumorigenicity by SV40-transformed mouse mammary epithelial cells. Super T-Ag may be most important as a marker of genomic rearrangements by the resident viral genes in transformed cells.

Animals↗
PubMed1986

Differential renal function during angiotensin converting enzyme inhibition in renovascular hypertension.

Renal function was measured sequentially in 32 patients with proven renovascular hypertension who were treated with the oral angiotensin converting enzyme inhibitor captopril. Renal function was assessed by serial measurement of serum creatinine. Six patients showed acute rises in serum creatinine concentration compatible with acute renal failure. Acute renal failure was confined to those patients with stenosis to a solitary kidney (transplant or native, occurring in 3 of 8 patients) or bilateral renal artery stenosis (occurring in 3 of 13 patients). No rise in serum creatinine concentration was observed in 11 patients with unilateral renal artery stenosis during long-term angiotensin converting enzyme inhibitor therapy. Acute renal failure during angiotensin converting enzyme inhibitor therapy was not related to the degree of blood pressure fall or the plasma angiotensin II level. Eleven patients with renovascular hypertension were followed prospectively with estimation of renal function by 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance (determined by computer analysis of scintillation camera renography). In six patients with unilateral renal artery stenosis, total 99mTc-DTPA clearance and serum creatinine level remained constant following angiotensin converting enzyme inhibitor therapy, while in five patients with bilateral renal artery stenosis 99mTc-DTPA clearance fell from 40 +/- 9 to 27 +/- 5 ml/min (p less than 0.05). Split renal function studies revealed that 99mTc-DTPA clearance fell in most kidneys with stenosed arteries during angiotensin converting enzyme inhibition, including the stenosed kidney from patients with unilateral renal artery stenosis (16 stenosed kidneys studied; change in Tc-DTPA clearance, -7.5 +/- 2.7 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1986

Dependence of subjective traverse length on velocity of moving tactile stimuli.

Two series of experiments were performed to assess the effects of stimulus velocity on human subjects' perception of the distance traversed by a moving tactile stimulus. In all experiments, constant-velocity stimuli were applied to the dorsal surface of the left forearm; velocities ranging between 1.0 and 256 cm/sec were used. In some experiments the stimuli moved from distal to proximal over the skin, and in others they moved from proximal to distal. The length of skin contacted by the moving stimulus was defined by a plate having an aperture of 4.0 X 0.5 cm. In the first series of experiments, subjects were required to compare the distance traversed by a test stimulus delivered 2 sec after a standard stimulus, and also to report the on-locus and the off-locus of the brushing stimulus. In the second series of experiments, the subjects rated the perceived distance on the skin using a free-magnitude-estimation procedure. The data from both series of experiments defined the same relationship between stimulus velocity and perceived stimulus distance. More specifically, although the length of skin contacted by the stimulus was the same at all velocities, subjects' estimates of stimulus distance decreased with increasing stimulus velocity. In addition, the function relating estimates of stimulus distance to velocity was flat for velocities between 5 and 20 cm/sec, but possessed an appreciable negative slope at lower and higher velocities. It is interesting that the plateau of the relationship between perceived stimulus distance and velocity occurred within the range of velocities that human subjects employ to scan textured surfaces; it also corresponded precisely with the range of stimulus velocities at which the directional sensitivity of somatosensory cortical neurons and human subjects is optimal.

Adult↗
PubMed1986

Characterization of a spontaneous mutation to a beta-thalassemia allele.

We have studied a nuclear family containing a single child with severe beta-thalassemia intermedia, a Greek-Cypriot mother with hematological findings of beta-thalassemia trait, and a Polish father who is hematologically normal. Since both the child and her father were heterozygous for a DNA polymorphism within the beta-globin gene, it was possible to clone and sequence the beta-globin gene identical by descent from both the child and her father. A nonsense mutation in codon 121 (GAA----TAA) was found in the beta-globin gene of the child, while the same gene from her father lacked this mutation and was normal. This mutation has not been previously observed among over 200 beta-thalassemia genes characterized in Caucasians. Since the mutation eliminates an EcoRI site in the beta-globin gene, we could show that the mutation is not present in genomic DNA of the father. To rule out germinal mosaicism, sperm DNA of the father was also digested with EcoRI, and the mutant EcoRI fragment was not observed under conditions that would detect the mutation if it were present in at least 2% of sperm cells. Routine HLA and blood group testing supported stated paternity. In addition, studies with 17 DNA probes that detect multiple allele polymorphisms increased the probability of stated paternity to at least 10(8):1. These data provide evidence that the G----T change in codon 121 of the beta-globin gene in the child is the result of a spontaneous mutation that occurred during spermatogenesis in a paternal germ cell.

Alleles↗
PubMed1986

Selective inhibition of proteolytic enzymes in an in vivo mouse model for experimental metastasis.

Peptide aldehyde transition state analogue inhibitors of serine and cysteine proteases have been used to selectively inhibit proteases for which prior evidence supports a role in tumor cell metastasis. These enzymes include cathepsin B, urokinase plasminogen activator (PA), and thrombin. The inhibition constants of the peptidyl aldehyde inhibitors show that they are highly selective for a particular targeted serine or cysteine protease. The inhibitors are introduced by i.p. injection or by miniosmotic pumps into syngeneic C57BL/6 mice also given injections of B16-F10 melanoma cells, and the number of metastatic foci in the lung was determined. While the injection protocol gave an initially high but changing in vivo concentration of inhibitor over time, the minipump implant gave a constant steady state concentration of inhibitor over 5-7 days. Minipump infusion of leupeptin (acetylleucylleucylargininal), a strong inhibitor of cathepsin B at a steady state plasma concentration 1000-fold greater than its Ki(cathepsin B), gave no significant decrease in lung colonization by the B16 tumor cells. Ep475, a stoichiometric irreversible peptide inhibitor of cathepsin B-like proteases, also did not significantly inhibit metastatic foci formation. Introduction of selective inhibitors of urokinase PA, tert-butyloxycarbonylglutamylglycyl-argininal and H-glutamylglycylargininal at concentrations near its Ki, produced no significant decrease in mouse lung colonization. The selective thrombin inhibitor D-phenylalanylprolylargininal infused to a steady state concentration 100-fold greater than its Ki dramatically increased B16 melanoma colonization of mouse lung. The results indicate that neither secreted cathepsin B-like nor urokinase PA have roles in B16 colonization of mouse lung, while thrombin may have a role in preventing metastasis. These experiments do not eliminate roles for a cathepsin B-like enzyme or urokinase PA in the initial steps of the metastatic process.

Animals↗
PubMed1986

Endotoxin-induced prostanoid production by the burn wound can cause distant lung dysfunction.

We injected Escherichia coli endotoxin, 2 micrograms/kg, beneath the eschar of sheep with 25% total body surface full-thickness burns to determine whether burn tissue in the presence of endotoxin releases prostanoids, particularly thromboxane A2, (TxA2), and if increased local TxA2 production can lead to distant lung dysfunction. We compared this response to the lung injury produced by the same dose given intravenously. We noted a marked increase in burn tissue TxA2 production after subeschar endotoxin as reflected in significant increases in burn lymph and pulmonary artery TxB2 levels. Pulmonary artery pressure increased from 22 to 38 mm Hg and PaO2 decreased from 89 to 71 torr while lung lymph flow (QL) increased only modestly with no evidence of increased lung permeability. The TxA2 production and the lung response were prevented by the subeschar injection of ibuprofen, 12.5 mg/kg. Circulating endotoxin was noted in only one of five sheep. After intravenous (endotoxin), a significant increase in lung TxA2 production was noted and a characteristic two-phase lung injury was seen with an initial phase basically identical to that seen with the subeschar injection followed by an increase in lung protein permeability. Burn tissue endotoxin can stimulate local TxA2 production leading to distant lung dysfunction without the need for circulating endotoxin. The source of the TxA2 is the burn, while with endotoxemia the source is the lung.

Animals↗
PubMed1985

Pulmonary dysfunction secondary to soft-tissue endotoxin.

Our purpose was to determine whether peripheral soft tissues produce and release prostanoids in response to local sepsis, and whether this mediator release can produce pulmonary dysfunction. Escherichia coli endotoxin (2 micrograms/kg in 100 mL of saline) was injected below the hide of the flank in seven unanesthetized sheep. In three additional sheep, ibuprofen (12.5 mg/kg of body weight) was injected with the endotoxin. Thromboxane B2 and 6-keto-PGF1 alpha (prostacyclin) levels were measured in tissue lymph draining the flank, lung lymph, pulmonary artery (Ppa), and aortic plasma. One hour after endotoxin administration, mean PaO2 decreased from 90 to 74 mm Hg and Ppa increased from 22 to 35 mm Hg. Lung lymph flow (QL) increased only 50% with QL being protein poor. No increase in lung or peripheral soft-tissue vascular permeability was noted. Tissue lymph (TxB2) increased from 220 +/- 114 to greater than 10,000 pg/mL with levels in Ppa plasma increasing from 300 +/- 128 to 595 +/- 124 pg/mL and aortic plasma from 270 +/- 141 to 410 +/- 104 pg/mL. Lung lymph TxB2 paralleled aortic values. Peak levels of 6-keto-PGF1 alpha in systemic lymph exceeded 2,000 pg/mL while levels in lung lymph remained relatively constant. The pulmonary injury and the increase in TxB2 was prevented by ibuprofen. We conclude that the response of soft tissue to local endotoxin is to release thromboxane in quantities sufficient to raise plasma levels and to produce hypoxia and pulmonary hypertension. The lung dysfunction is not produced by an increase in lung water or vascular permeability.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Spontaneous in vitro production of anti-DNA and anti-RNA by systemic lupus erythematosus and normal peripheral blood mononuclear cells.

The spontaneous in vitro production of anti-DNA and anti-RNA by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) and from normal subjects was evaluated employing sensitive solid-phase assays that are specific for these antibodies. PBMC from SLE patients produced more IgG anti-DNA and anti-RNA than did normal PBMC (P less than 0.01). In vitro production of IgG anti-DNA appeared to correlate with serum DNA bindings (r = 0.72, P less than 0.005). Similar amounts of IgM anti-DNA and anti-RNA were produced by both SLE and normal PBMC. However, IgM anti-DNA antibodies always appeared to be directed against determinants on denatured DNA. Only PBMC from SLE patients produced IgG antibodies to native DNA.

Antibodies↗
PubMed1985

Rat liver alkaline phosphatases. Evidence hepatocyte and portal triad enzymes differ.

Using biochemical and electron microscopic histochemical techniques, we studied membrane-bound alkaline phosphatase activities of rat hepatocytes and portal triads. Activity in portal triads was localized to capillaries surrounding bile ducts (peribiliary plexus) and arterioles. Despite the reputation of alkaline phosphatase as a "biliary enzyme," activity was not observed in bile ducts. Livers were separated into hepatocyte and portal triad fractions with collagenase. Enzyme from hepatocytes migrated faster during electrophoresis and eluted later during anion-exchange chromatography than that from portal triads. Thus, hepatocyte enzyme is more negatively charged (and also possibly smaller) than portal triad enzyme. Twelve hours after bile duct obstruction, new activity appeared on lateral and sinusoidal membranes of hepatocytes; appearance of portal triads did not change with obstruction. Electrophoretic mobilities of the two forms were not altered by obstruction. We conclude that two distinct liver alkaline phosphatases exist, one in hepatocytes, the other in portal triad blood vessels.

Alkaline Phosphatase↗
PubMed1985

Responses of the pigmented rabbit retina to NMPTP, a chemical inducer of parkinsonism.

The electrophysiological and neurochemical effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP), a chemical inducer of Parkinsonism in man and monkeys, on the pigmented rabbit retina were determined under both chronic and acute conditions. The implicit time, the oscillatory potentials, and the amplitude of the b-wave of the rabbit electroretinogram were affected; both dopamine and dihydroxyphenylalanine (DOPA) levels were depressed. Ultrastructural analysis of acute and chronic retinas showed the occurrence of an intranuclear filamentous inclusion in the nucleus of some cells in the inner nuclear and ganglion cell layer of chronic samples. The effects of the neurotoxin NMPTP on the retina suggest that dopaminergic metabolism is impaired, which then affects the components of the electroretinogram attributed to both bipolar and amacrine cells. In addition, the retina may provide a model in which to study the bichemical and pharmacological mechanisms of NMPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗