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Biomedical subjects

F Wong

Publications and source records attributed to F Wong.

At least 163 records · Page 9Linked to original sources
PubMed1993

Involvement of lipids in membrane binding of mouse hepatitis virus nucleocapsid protein.

Evidence is presented which indicates that membrane binding of the MHV nucleocapsid (N) protein is influenced by membrane lipid composition. Binding of N protein to membranes of mouse fibroblast L-2 cells is very specific and occurs under conditions in which no other viral or cellular proteins show detectable binding. Binding occurs rapidly and does not require the presence of divalent cations such as Ca++ or Mg++. Purified phospholipid liposomes compete against N protein binding to membranes. Phospholipids consisting of cardiolipin are the most effective in inhibiting membrane binding. Because of certain structural similarities between phospholipids and nucleic acids, we speculate that membrane lipid association of the N protein may compete for RNA binding sites on the N protein. Such a mechanism may be important for processes such as nucleocapsid uncoating and nucleocapsid assembly.

Animals↗
PubMed1993

Indomethacin-induced renal dysfunction in patients with well-compensated cirrhosis.

BACKGROUND: Patients with cirrhosis and ascites are especially sensitive to the adverse renal effects of indomethacin-induced inhibition of prostaglandin synthesis. The aim of this study was to determine whether indomethacin affects renal function in patients with well-compensated cirrhosis. METHODS: Clearance techniques were used to assess renal hemodynamics and sodium and water homeostasis. RESULTS: The oral administration of 50 mg of indomethacin to well-compensated patients with alcoholic cirrhosis was followed by a significant decrease in glomerular filtration rate (GFR) and effective renal plasma flow because of a preferential increase in afferent arteriolar tone. Indomethacin was both antidiuretic and antinatriuretic due principally to decreased free water clearance and increased proximal tubular reabsorption of sodium. The acute changes in renal function were not sustained. Patients with a high basal GFR were particularly sensitive to the adverse renal effects of indomethacin. CONCLUSIONS: This study indicates that in patients with well-compensated cirrhosis renal prostaglandins are functionally active and may contribute to the pathogenesis of glomerular hyperfiltration. Nonsteroidal anti-inflammatory drugs should be used with caution in all patients with cirrhosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Glomerular hyperfiltration in patients with well-compensated alcoholic cirrhosis.

BACKGROUND: Peripheral and splanchnic arteriolar tone is often decreased in patients with cirrhosis. The responsible circulating vasodilator(s) would be expected to also lower renal vascular resistance. To examine this possibility we have undertaken a hemodynamic study of the renal circulation in patients with stable, well characterized, compensated cirrhosis and in healthy controls of similar age and sex. METHODS: Clearance techniques were used to assess splanchnic and renal hemodynamics and hepatocellular function. RESULTS: Renal vascular resistance was significantly reduced in the cirrhotic patients (P = 0.048) and was accompanied by a significant (P = 0.014) and proportional (r = -0.45; P = 0.016) increase in glomerular filtration rate. The hepatic extraction of indocyanine green, a measure of functional intrahepatic portasystemic shunts, was the only independent predictor of glomerular filtration rate (r = -0.65; P = 0.002). CONCLUSIONS: The results support the hypothesis that, in patients with cirrhosis, the presence of portasystemic shunts results in an increased delivery of endogenous vasodilator(s) into the systemic circulation where their principal action on the renal circulation is to preferentially decrease afferent arteriolar tone. The resultant glomerular hyperfiltration may contribute to the pathogenesis of cirrhotic glomerulosclerosis.

Adult↗
PubMed1993

Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice.

Mutations in the retinal degeneration, retinal degeneration slow(/peripherin) and rhodopsin genes cause photoreceptor degeneration in humans and mice. Although the phenotypes arising from these mutations are different, suggesting different mechanisms of pathogenesis, we present evidence that apoptosis may be the final common pathway of the disease process linking genotype to phenotype. We observed internucleosomal cleavage of retinal DNA by gel electrophoresis and fragmented DNA at the single cell level by labeling the nicked DNA ends with biotinylated poly(dU). In retinal degeneration mice, DNA fragmentation occurred during the period of photoreceptor degeneration. In retinal degeneration slow mice and in transgenic mice expressing a mutant (Pro347Ser) rhodopsin gene, DNA fragmentation occurred after normal histogenetic cell death (also apoptosis) had ceased. Since DNA fragmentation by internucleosomal cleavage is a cardinal feature of apoptosis, our data suggest that all three of these genetic mutations lead to apoptosis.

Amino Acid Sequence↗
PubMed1993

Serum ultrafiltrable copper, total copper and caeruloplasmin concentrations in gynaecological carcinomas.

Serum copper and caeruloplasmin concentrations are elevated in various carcinomas, but it is not known whether the rise in serum copper is due to elevation of caeruloplasmin alone or whether it is also due to the elevation of 'free' copper. We therefore determined ultrafiltrable copper to answer this question. Serum ultrafiltrate was prepared using the Amicon micropartition system and ultrafiltrable (free) copper was determined by flameless atomic absorption spectrophotometry. Serum total copper was determined by flame atomic absorption spectrometry and caeruloplasmin by rate nephelometry. There was no significant difference in the ultrafiltrable copper concentration between patients with gynaecological tumours and control subjects. However, total copper and caeruloplasmin concentrations were significantly elevated in cancer patients compared with control subjects. In contrast to total copper and caeruloplasmin concentrations, ultrafiltrable copper concentrations showed no significant increase with increase in the stage of the cancer.

Adult↗
PubMed1993

Expression of three forms of melanoma growth stimulating activity (MGSA)/gro in human retinal pigment epithelial cells.

PURPOSE: To characterize mRNA expression and protein production of the cytokine MGSA/gro in human retinal pigment epithelial (RPE) cells and to determine whether expression of MGSA/gro is modulated by serum and the cytokines interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), or transforming growth factor beta (TGF beta) mediators implicated in proliferative vitreoretinopathy (PVR). METHODS: Reverse-transcription polymerase chain reaction was used to determine the steady-state mRNA expression of three forms of MGSA/gro, alpha, beta, and gamma, by cultured human RPE cells in the presence or absence of recombinant IL-1 beta, TNF alpha, or TGF beta, or when serum-starved cells were re-fed with medium containing serum. Immunocytochemistry was used to characterize RPE cell-associated MGSA/gro protein, and immunoprecipitation of MGSA/gro from cell-conditioned medium was used to demonstrate MGSA/gro secretion. RESULTS: MGSA/gro mRNA was expressed minimally under basal conditions. Expression for all three forms of MGSA/gro mRNA was induced in a dose- and time-dependent manner after exposure to IL-1 beta, to a lesser extent after exposure to TNF alpha, but not after exposure to TGF beta. Serum induced MGSA/gro alpha and gamma transcripts, but not beta transcripts. Cell-associated MGSA/gro was identified on RPE cells grown in the absence of cytokines, but MGSA/gro was not secreted under these conditions. Exposure to IL-1 beta did not consistently cause increased cell-associated MGSA/gro; however, IL-1 beta induced secretion of MGSA/gro in a time-dependent manner. CONCLUSION: MGSA/gro is produced by human RPE in response to mediators implicated in PVR. Because MGSA/gro is a pleiotropic modulator of cell proliferation and inflammation, it may contribute to the intraocular wound healing response that characterizes PVR.

Blood Proteins↗
PubMed1993

Refractory ascites in cirrhosis: roles of volume expansion and plasma atrial natriuretic factor level elevation.

Cirrhotic patients with ascites refractory to diuretics also have blunted response to marked elevations of plasma atrial natriuretic factor levels alone or to moderate intravascular volume expansion by head-out water immersion. However, these patients usually undergo natriuresis after peritoneovenous shunting. To dissect the factors responsible for this response, we studied the effects on separate days of moderate intravascular volume expansion and highly elevated plasma atrial natriuretic factor levels (head-out water immersion and atrial natriuretic factor infusion) or marked volume expansion and moderate plasma atrial natriuretic factor level elevation (head-out water immersion and albumin infusion) in 13 alcoholic cirrhotic patients with massive ascites. Three of these patients, who responded to initial head-out water immersion with a negative sodium balance, served as controls. Unresponsiveness to head-out water immersion was confirmed in the remaining 10 patients on both days on the basis of blunted natriuretic response (urinary sodium excretion < 0.8 mmol/hr after 2 hr). In contrast, these 10 refractory patients were able to achieve negative sodium balance with both combinations. Mean urinary sodium excretion increased from a baseline level of 0.13 +/- 0.10 mmol/hr to a peak level of 2.29 +/- 0.61 mmol/hr after head-out water immersion and atrial natriuretic factor infusion and from 0.10 +/- 0.3 mmol/hr to 1.61 +/- 0.62 mmol/hr after head-out water immersion and albumin infusion. Both maneuvers were associated with suppression of plasma renin activity and serum aldosterone levels. With head-out water immersion and atrial natriuretic factor infusion, we noted a significant increase in 5' cyclic GMP levels, a second messenger of atrial natriuretic factor, indicating possible activation of atrial natriuretic factor receptors at the inner medullary collecting ducts. In contrast, with head-out water immersion and albumin infusion no such increase in levels occurred, indicating that the increase in urinary sodium excretion was mainly due to increased delivery of sodium to the cortical distal nephron, as indicated by a disproportionate increase in urinary potassium excretion. In conclusion, massive (as opposed to moderate) volume expansion or greatly elevated levels of plasma atrial natriuretic factor associated with moderate volume expansion can improve blunted atrial natriuretic factor responsiveness in cirrhotic patients with refractory ascites. This appears to be achieved by way of a marked increase in distal delivery of filtrate in the kidney, with or without activation of distal atrial natriuretic factor receptors in the inner medullary collecting ducts.

Adult↗
PubMed1992

A novel regulatory myosin light chain gene distinguishes pre-B cell subsets and is IL-7 inducible.

We describe a novel regulatory myosin light chain gene (termed precursor lymphocyte-specific regulatory light chain or PLRLC) that is expressed specifically in precursor B and T lymphocytes. PLRLC is the first example of a regulatory myosin light chain gene which displays specific expression in non-muscle cells. PLRLC is expressed in adult bone marrow derived normal and transformed pre-B cells; in the former, PLRLC expression levels are induced by the pre-B cell specific growth factor interleukin-7 (IL-7). PLRLC is not expressed in either transformed pre-B cells derived from fetal liver or in normal fetal liver pre-B clones grown in the presence of IL-7. Therefore this gene provides the first marker that clearly distinguishes these two pre-B subsets. Finally, several of the different PLRLC transcripts potentially encode regulatory myosin light chains with unique structural features. The unique distribution, regulation and structural features of the PLRLC gene products suggest an important role for PLRLC during lymphocyte development.

Amino Acid Sequence↗
PubMed1992

Ascorbic acid modulates collagen type I gene expression by cells from an eye tissue--trabecular meshwork.

The trabecular meshwork, a specialized tissue in the anterior chamber of the eye, plays a major role in the regulation of aqueous humor outflow. We studied the effects of ascorbic acid, a significant component in the aqueous humor, on gene expression of type I collagen in cultures of bovine trabecular meshwork cells. These cells were plated for 6 days, exposed to ascorbic acid in concentrations of 100, 250 and 500 micrograms/ml for 3 days and labeled with (3H)proline for the last 24 hrs. Cultures that did not receive ascorbic acid served as controls. Bacterial collagenase assays showed enhanced incorporation of (3H)proline into collagenous proteins in cultures treated with 100 and 250 micrograms/ml of ascorbic acid. Gel electrophoresis and fluorography revealed that ascorbic acid caused a 2.6- to 4.9-fold increase in production of alpha 1 (I) and alpha 2(I) collagen chains by trabecular meshwork cells. Such an increase was found, using a cDNA probe specific for pro alpha 1(I) chains, to be accompanied by an increase in steady-state mRNA levels. Similar findings were also yielded from in situ hybridization experiments. These results, coupled with previously demonstrated ascorbate-induced effects on glycosaminoglycan, fibronectin and laminin synthesis, suggest that ascorbic acid is a key mediator of the extracellular matrix production by trabecular meshwork cells. Fluctuations in its concentration may lead to alterations in the makeup and assembly of matrices underlying the cells.

Animals↗
PubMed1991

Hygromycin B therapy of a murine coronaviral hepatitis.

Hepatitis caused by mouse hepatitis virus (MHV-A59), a murine coronavirus, is accompanied by direct infection and replication of virus within the liver. We demonstrate here that the aminoglycoside hygromycin B is able to eliminate MHV-A59 infection from mouse peritoneal macrophages and cultured liver cells in vitro and is also able to reduce levels of virus replication and necrotic liver foci in vivo.

Animals↗
PubMed1990

On the membrane cytopathology of mouse hepatitis virus infection as probed by a semi-permeable translation-inhibiting drug.

Previous studies of the membrane fusion process have permitted the characterization of membrane permeability changes concomitant with MHV-induced cytopathology. One indication of membrane permeability in MHV-infected cells is their sensitivity to translation inhibition by the normally impermeable amino-glycoside, hygromycin B (Macintyre, G., Wong, F. and Anderson, R. (1989) J. Gen. Virol. 70, 763-768). In the present study, we examine the hygromycin B sensitivity of acutely infected mouse fibroblast L-2 cell and macrophage cultures as well as persistently infected mouse fibroblast LM-K cell cultures. The results suggest that membrane permeability alterations (as indicated by hygromycin B sensitivity) are a common feature of these MHV infections. Hygromycin B "cured" persistently infected LM-K cells as indicated by the absence of detectable virus antigen by immunofluorescence and by the absence of infectious virus even after removal of the drug or co-cultivation with untreated L-2 cells. The results argue against the maintenance of MHV infection by a mechanism involving latently or non-cytolytically infected cells. We conclude therefore that at least one mechanism for MHV persistence depends on virus propagation by cytolytic infection of a small, dynamically changing, fraction of the total cells present in culture.

Animals↗
PubMed1990

Mouse fibroblast mutants selected for survival against mouse hepatitis virus infection show increased resistance to infection and virus-induced cell fusion.

We describe here a genetic approach to the analysis of host cell functions involved in determining permissiveness to mouse hepatitis virus (MHV). Using the chemical mutagen, ethyl methane sulfonate (EMS), mouse fibroblast cell mutants were generated which were selected for resistance to cell-killing by MHV. These mutants were then screened for their susceptibility to MHV infection, ability to replicate MHV and relative sensitivity to MHV-induced cell fusion. In contrast to wild type L-2 cells which were acutely and terminally infected by MHV, all five mutants examined replicated MHV in a persistent manner. These mutants showed a reduced susceptibility to MHV infection and an increased resistance to MHV-induced cell fusion. Fusion resistance was specific to that mediated by the MHV E2 protein; mutant as well as wild type L-2 cells were equally sensitive to fusion by polyethylene glycol. The combined effect of reduced infectability and increased fusion resistance was to limit MHV infection to only a small percentage of the total cells in culture, thereby permitting survival of both virus and cells. The observed high rate of generation of the cell mutants suggests that the conversion of a fully MHV-susceptible cell to a semi-resistant one (capable of supporting a persistent infection) is a fairly common event, possibly involving a single mutation.

Animals↗
PubMed1990

Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins.

The progestational and androgenic in vitro receptor binding affinity and the in vivo activity of norgestimate was compared with that of its metabolites and other progestins. The relative binding affinities (RBAs) of norgestimate and its 17-deacetylated metabolite for rabbit uterine progestin receptors were similar to that of progesterone (P); those of 3-keto norgestimate and levonorgestrel were about five times that of P; those of gestodene and 3-keto desogestrel were about nine times that of P. The RBAs of norgestimate, P, and 3-keto norgestimate for rat prostatic androgen receptors were from 0.003 to 0.025 times that of dihydrotestosterone (DHT); those of 3-keto desogestrel, gestodene, and levonorgestrel were from 0.118 to 0.220 times that of DHT. The order of receptor level selectivity represented by the ratio of androgen:progestin IC50 values (with a greater ratio value reflecting a better selectivity) was norgestimate greater than P = 3-keto norgestimate greater than 17-deacetylated norgestimate greater than 3-keto desogestrel greater than gestodene greater than levonorgestrel. In vivo studies demonstrated similar profiles for norgestimate and its 17-deacetylated metabolite. These latter two steroids were equally potent as progestins in stimulating rabbit endometrium, and compared with the other progestins, both steroids exhibited minimal androgenicity as measured by the stimulation of rat prostate growth. In conclusion, these studies, as well as previous preclinical and clinical studies, provide evidence of the selectivity of norgestimate based on minimal androgenicity, indicating an improvement over other progestins used in oral contraceptives.

Animals↗
PubMed1990

The usefulness of ultrasonography in intracavitary radiotherapy using selectron applicators.

Uterine perforation can occur during the procedure of intracavitary insertions for the treatment of carcinoma of the cervix. If radiation treatment proceeds in the situation of inadvertent perforation, severe complication may result. The ultrasonographic studies of five patients with metal intrauterine applicators in situ are described. The applicator appeared as a linear echogenic density within the uterine cavity. The thickness of the uterine wall and the fundus could be clearly identified in a normal insertion. In the presence of uterine perforation, the applicator was seen traversing the myometrium necessitating alteration of the treatment plan.

Brachytherapy↗
PubMed1990

An immunopathologic study of retinoblastoma protein.

We investigated the immunoreactivity of the retinoblastoma protein in eight retinoblastoma tumors of different stages of differentiation. All undifferentiated tumor cells failed to show immunoreactivity. In one patient, who had a family history of retinoblastoma and had been treated by radiation, the tumor had a large area of undifferentiated cells and small independent retinocytomas. The tumor cells in the retinocytoma and the cone cells in the adjacent retina, but not the undifferentiated tumor cells, showed positive staining with two anti-Rb antibodies. The immunoreactivity may be related to radiation or differentiation of retinoblastoma and cone cells.

Child, Preschool↗
PubMed1989

Treatment of oral leukoplakia with topical bleomycin. A pilot study.

Leukoplakia is a clinical diagnosis with the potential for malignant transformation. This pilot study tested the use of bleomycin a as topical agent for the treatment of leukoplakia. Twelve patients were enrolled in this study, each for 2 weeks of daily topical application of bleomycin in dimethylsulphoxide (DMSO) painted over the lesion. Two patients were excluded from analysis due to excessive dilution of the medication by local saliva production. Five patients were treated with a 0.5% solution that caused a decrease in the thickness of all of the lesions clinically. One lesion also had a sharp decrease in size. Five patients were treated with a 1.0% solution that caused a complete resolution of the lesions in three patients. Two lesions demonstrated maturation of parakeratosis to keratosis only. All patients tolerated the treatments well. Topical bleomycin may play a role in the treatment of leukoplakia and warrants further investigation.

Administration, Topical↗