Biomedical subjects

H L Wong

Publications and source records attributed to H L Wong.

At least 19 recordsLinked to original sources

PubMed2006

Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural and nonagricultural sites in Michigan (USA).

In vitro studies have demonstrated atrazine-mediated induction of 7-ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the metabolism of many compounds, including many xenobiotics. These studies have suggested that atrazine may affect reproductive function by altering steroid metabolism. The goal of this study was to determine whether relationships could be detected between measured atrazine concentrations in surface waters and the liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD) activities in the livers of ranid frogs. In addition, sediment dioxin toxic equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south central Michigan in the summer of 2003. Atrazine concentrations at nonagricultural sites ranged from less than the limit of quantification (0.17 microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one agricultural site. Of the measured parameters, only LSI values in adult male frogs differed significantly between agricultural and nonagricultural sites, with greater values observed at agricultural sites. In green frogs, EROD and MROD activities were measurable in both adult and juvenile frogs and were similar among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs. Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine concentrations were significantly and negatively correlated with MROD activity in adult male green frogs (Spearman R = -0.800). LSI and EROD and MROD activities of adult female or juvenile green frogs were not significantly correlated with atrazine concentrations. These results suggest that atrazine does not appear to have a consistent association with EROD or MROD activities in wild-caught green frogs.

Agriculture↗

PubMed2005

Organochlorine insecticides in mudflats of Hong Kong, China.

Organochlorine (OC) insecticides were measured in different environmental compartments (including seawater, sediment, and biota) at six sites within the Mai Po Marshes Nature Reserve (MPMNR) and at one site in A Chau (AC) in Hong Kong in June 2002 (wet season) and January 2003 (dry season). MPMNR is a Wetland of International Importance (Ramsar site) situated in the western part of Hong Kong, whereas AC is a relatively remote island in Starling Inlet on the eastern side of the New Territories of Hong Kong. Generally, concentrations of OC insecticides in water, sediment, and biota were greater at MPMNR than at AC. Hexachlorobenzene, dichloro-diphenyl-trichloroethane, and hexachlorocyclohexanes were detected in all samples collected from MPMNR. Preliminary risk assessments were performed by comparing the measured concentrations of OCs in different environmental compartments with the corresponding guidelines promulgated by various environmental protection authorities. Concentrations of some OCs in sediments from certain locations in MPMNR were consistently greater than their corresponding sediment guideline values. These results suggest that the sediment OC concentrations in the sediments of MPMNR might pose a risk to aquatic organisms. Despite this, concentrations of OCs in biota samples were much lower than the relevant guideline values promulgated by government agencies to protect the health of human consumers. It is postulated that the management practices adopted at MPMNR have been effective in limiting the bioaccumulation window (duration) for OCs. This situation may have been aided by a frequent exchange of water between the tidal shrimp ponds at MPMNR and the open sea, again attributable to management practices. The low-cost maintenance practices adopted at MPMNR may potentially be applicable to wetlands in other southeastern Asian countries, thus allowing sustainable fishery production and wildlife conservation.

Animals↗

PubMed2005

Risks posed by trace organic contaminants in coastal sediments in the Pearl River Delta, China.

Local marine environments in China's Pearl River Delta (PRD), the most rapidly developing region in one of the world's fastest growing economies, have been experiencing significant environmental stress during the past decades. This investigation was conducted to determine the status and trends of persistence organic pollutants (POPs) such as polycyclic aromatic hydrocarbons (PAHs), petroleum hydrocarbons (PHCs), polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides and dioxin-related compounds in marine sediments collected from sixteen coastal stations in the Pearl River Delta (PRD) in March 2003. Elevated concentrations of PAHs (94-4300 ng/g), PCBs (6.0-290 ng/g), PHCs (14-150 microg/g), and DDTs (1.4-600 ng/g) were detected in sediment samples. In addition, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activities in the sediment samples were estimated to range from 0.3 to 440 pg TCDD-EQ/g. Sediments collected from Xiashan contained the greatest concentrations of trace organic contaminations amongst all the sampling stations in the present study. The degree of trace organic contamination was, in general, more severe at stations situated along the west shores of the PRD than their counterparts in the east. A preliminary assessment was performed to examine the probable risks to the marine ecosystem due to POPs. The results showed that OC pesticide contamination in the PRD was particularly serious and might pose a threat to the health of the marine inhabitants.

China↗

PubMed2005

Estrogenic and dioxin-like activities and cytotoxicity of sediments and biota from Hong Kong mudflats.

Persistent organic pollutants, such as organochlorine insecticides and polychlorinated biphenyls (PCBs), were measured in several environmental matrices including aerial deposition, seawater, sediment, and biota in two important coastal wetlands of Hong Kong, China. Specifically, samples were collected from within the Mai Po Marshes Nature Reserve (Mai Po), an internationally acclaimed wetland situated in the northwestern part of the New Territories of Hong Kong, and A Chau in Starling Inlet, a relatively remote island on the eastern side of Hong Kong. Hexachlorobenzene, dichlorodiphenyltrichloroethanes, and hexachlorocyclohexanes were detected in all samples collected from Mai Po. Environmental endocrine disruptors (including dioxin-like compounds and estrogenic chemicals), measured by the use of cell-based chemical activated luciferase expression assays, were found to occur at concentrations that might pose a risk to the ecologic systems in Mai Po. Dioxin-like PCBs were detected at small concentrations in some of the samples. Concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin equivalents (TEQs) were primarily related to the relatively great concentrations (>100 ng/g dry weight) of high molecular-weight polycyclic aromatic hydrocarbons in sediments, whereas the relative proportion of TEQs contributed by nonortho-substituted PCBs was small. Polar compounds primarily contributed estrogen equivalents, which were measured in sediments. Significant concentrations of cytotoxic compounds were detected in fish samples collected from the Mai Po but not in fish collected from A Chau.

Animals↗

PubMed2005

Human health risk assessment of organochlorines associated with fish consumption in a coastal city in China.

Food consumption is an important route of human exposure to organochlorines (OCs). In order to assess the potential health risks associated with these contaminants due to fish consumption, five species of fish were collected from a local market in Zhoushan City, an island in the East China Sea. Dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins/ dibenzofurans, in the fish samples were screened by H4IIE-luc cell bioassay, and the concentrations of specific organochlorines were measured by gas chromatograph-electron capture detector (GC-ECD). The bioassay results indicated that concentrations of dioxin-like compounds in the fish samples were below detection limit (0.64 pg/mL). The concentrations of OC pesticides and PCBs ranged from 0.67 to 13 and 0.24 to 1.4 ng/g wet wt., respectively. Significantly, concentrations of p,p'-DDE in fish meat were comparatively high (average 3.9 ng/g wet wt.) compared with the other OC pesticides. The daily fish consumption, based on a dietary survey conducted among 160 local healthy residents, was determined to be 105 g/person. The relevant cancer benchmark concentrations of HCB, dieldrin, chlordane, DDTs and PCBs were 0.36, 0.04, 1.6, 1.7, and 0.29 ng/kg per day, respectively, based on the local diet. The hazard ratios (HRs), based on non-cancer endpoints were all less than 1.0, while the HRs based on cancer were greater than 1.0 for certain contaminants based on the 95th centile concentration in fish tissue.

Adult↗

PubMed2004

Epstein-Barr virus latent membrane protein 1 (LMP1) upregulates Id1 expression in nasopharyngeal epithelial cells.

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded LMP1 has cell transformation property. It suppresses cellular senescence and enhances cell survival in various cell types. Many of the downstream events of LMP1 expression are mediated through its ability to activate NF-kappaB. In this study, we report a novel function of LMP1 to induce Id1 expression in nasopharyngeal epithelial cells (NP69) and human embryonal kidney cells (HEK293). The Id1 is a basic helix-loop-helix (bHLH) protein and a negative transcriptional regulator of p16(INK4a). Expression of Id1 facilitates cellular immortalization and stimulates cell proliferation. With the combination of both specific chemical inhibitors and genetic inhibitors of cell signaling, we showed that induction of Id1 by LMP1 was dependent on its NF-kappaB activation domain at the carboxy-terminal region, CTAR1 and CTAR2. Induction of Id1 by LMP1 may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV and may promote their malignant transformation.

Carcinoma↗

PubMed2004

Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birthweight infants.

OBJECTIVE: To assess the incidence of late onset (> 72 hours) infection and necrotising enterocolitis (NEC) in very low birthweight (VLBW) infants in two 36 month periods using two hand hygiene protocols: conventional handwashing (HW; first 36 month period); an alcohol hand rub and gloves technique (HR; second 36 month period). METHOD: VLBW infants admitted to the neonatal intensive care unit during the period December 1993-November 1999 were eligible. A new hand hygiene protocol using alcohol handrub and gloves was introduced in December 1996. Each patient's case record was reviewed retrospectively by two independent investigators using a standard data collection form. The incidence of NEC and systemic infections, including bacterial or fungal septicaemia, meningitis, and peritonitis, in the two periods were compared. RESULTS: The HW and HR groups contained 161 and 176 VLBW infants respectively. The incidence of late onset systemic infection decreased from 13.5 to 4.8 episodes (including NEC)/1000 patient days after introduction of the HR regimen, representing a 2.8-fold reduction. Similarly, the incidence of Gram positive, Gram negative, and fungal infections decreased 2.5-fold, 2.6-fold, and 7-fold respectively. There was also a significant reduction in the incidence of NEC in the HR group (p < 0.0001). Subgroup analysis revealed that the incidence of methicillin resistant Staphylococcus aureus (MRSA) septicaemia was significantly decreased in the second 36 month period (p = 0.048). The clinical data suggest that infants in the HW group had significantly earlier onset of sepsis (p < 0.05) and required oxygen supplementation for longer (p < 0.05) than those in the HR group. Significantly more VLBW infants were discharged from the neonatal intensive care unit without ever being infected (p < 0.0001), and also significantly fewer infants had more than one episode of infection in the HR group (p < 0.0001). CONCLUSION: The introduction of the HR protocol was associated with a 2.8-fold reduction in the incidence of late onset systemic infection, and also a significant decrease in the incidence of MRSA septicaemia and NEC in VLBW infants. This decrease in infection rate was maintained throughout the second 36 month period.

2-Propanol↗

PubMed2003

Exposure and time dependent DNA strand breakage in hepatopancreas of green-lipped mussels (Perna viridis) exposed to Aroclor 1254, and mixtures of B[a]P and Aroclor 1254.

Green-lipped mussels (Perna viridis) were exposed to Aroclor 1254 (0.5, 5 and 50 microgl(-1)) and a mixture of benzo[a]pyrene (B[a]P) and Aroclor 1254 (0.3+0.5 and 3+5 microgl(-1)) for 12 days. On day 0, 1, 3, 6 and 12, the levels of DNA strand breaks in the mussel hepatopancreas were monitored using an alkaline unwinding assay. The results were compared to the findings of a previous study in which the levels of DNA strand breakage in the same species were measured following exposure to various concentrations of B[a]P (0.3, 3 and 30 microgl(-1)). The results indicated that Aroclor 1254 at a concentration </=50 microgl(-1) did not cause any increase in DNA strand breaks while B[a]P at concentrations ranging from 0.3 to 3 microgl(-1) caused an increase in strand breaks after one day of exposure, followed by an apparent rapid recovery. In contrast, exposure to 30 microgl(-1) B[a]P caused no increase in DNA strand breaks over the exposure period. This was postulated to be due to an early elicitation of the DNA repair system by the relatively high exposure level of B[a]P. This hypothesis was tested in the present study, and the results suggest that exposure to the high B[a]P concentration might have elicited the defense mechanism within the mussels, resulting in no observed increase in DNA strand breaks. An increase in strand breaks was, however, evident when the mussels were exposed to lower B[a]P levels. The levels of DNA strand breaks were correlated with the body burden of B[a]P and Aroclor 1254 but no significant relationship was observed, possibly owing to the rapid metabolism of the toxicant and/or an effective DNA repair mechanism. As a result, DNA strand breakage in the hepatopancreas of green-lipped mussels may not be a suitable biomarker of exposure to the above toxicants in the marine environment. Our findings also suggest that it would be instructive to investigate (1) the role of DNA repair enzymes in the exposed mussels; and (2) the correlation between the activity of these enzymes and the body burden of specific toxicants.

Analysis of Variance↗

PubMed2003

Effect of size, tissue parts and location on six biochemical markers in the green-lipped mussel, Perna viridis.

The effect of size and tissue parts as well as site locations on a suite of six anti-oxidative biochemical markers, viz. the enzyme degrading neural transmitters acetylcholinesterase (AChE), the Phase II transforming enzyme glutathione-S-transferase (GST), the anti-oxidative enzymes superoxide dismutase (SOD) and catalase (CAT), the lipid metabolite malondialdehyde (MDA) and the ratio of CAT/MDA, in the bivalve mollusc, Perna viridis, was studied. Field mussels were collected from the piers of University of Science and Technology (UST), Pak Sha Wan or Hebe Haven (PS) and Sai Kung (SK) in Port Shelter, Hong Kong. Statistically, ANOVA showed that the activity of all six biochemical markers were generally tissue dependent, size independent and location dependent. Tukey multi comparison test indicated that the biochemical activities fell into two groups, with SK the highest activity group in most cases. The significance of these findings in relation to long-term coastal water biomonitoring is discussed.

Acetylcholinesterase↗

PubMed2001

Essential role of the small GTPase Rac in disease resistance of rice.

Production of reactive oxygen intermediates (ROI) and a form of programmed cell death called hypersensitive response (HR) are often associated with disease resistance of plants. We have previously shown that the Rac homolog of rice, OsRac1, is a regulator of ROI production and cell death in rice. Here we show that the constitutively active OsRac1 (i) causes HR-like responses and greatly reduces disease lesions against a virulent race of the rice blast fungus; (ii) causes resistance against a virulent race of bacterial blight; and (iii) causes enhanced production of a phytoalexin and alters expression of defense-related genes. The dominant-negative OsRac1 suppresses elicitor-induced ROI production in transgenic cell cultures, and in plants suppresses the HR induced by the avirulent race of the fungus. Taken together, our findings strongly suggest that OsRac1 has a general role in disease resistance of rice.

Agrobacterium tumefaciens↗

PubMed2001

Oxygen consumption and resting energy expenditure during phototherapy in full term and preterm newborn infants.

OBJECTIVES: To determine the effect of phototherapy on the oxygen consumption and resting energy expenditure of term and preterm newborn infants. METHODS: A total of 202 infants (gestation 30-42 weeks; body weight 1270-4100 g) requiring phototherapy for the treatment of neonatal hyperbilirubinaemia were enrolled in a randomised crossover study. In random sequence, the oxygen consumption and resting energy expenditure were measured twice in each infant by indirect calorimetry, once at the end of six hours of continuous phototherapy and once after a control period of at least six hours without phototherapy. Anterior abdominal wall temperature was servocontrolled at 36.5 degrees C throughout the study. RESULTS: At the end of six hours of continuous phototherapy, oxygen consumption (mean (SD): 6.21 (1.35) v 6.26 (1.51) ml/kg, p = 0.555) and resting energy expenditure (178.11 (37.62) v 180.37 (43.14) kJ/kg/24 h, p = 0.382) did not differ significantly from those measured after the control period. There were also no significant differences in heart rate, respiratory rate, or rectal temperature. Subgroup analysis of those of gestation < 37 weeks or < 34 weeks also showed no effect of phototherapy on either oxygen consumption or resting energy expenditure. CONCLUSION: Phototherapy has no effect on the metabolic rate of thermally stable term or preterm infants.

Basal Metabolism↗

PubMed2000

In vitro studies and modeling of a controlled-release device for root canal therapy.

Endodontic disease is caused primarily by bacteria that interact with periradicular host tissues. Therefore, treatment of endodontic disease aims at the exclusion of bacteria from the root canal system. This work focused on in vitro studies and modeling of a controlled-release device for delivering antimicrobial agents in root canals. A cylindrical, needle-shaped device was prepared consisting of a matrix core and a polymer coating, loaded with 30-45% chlorhexidine (CHX). The composition of the core, a blend of water-permeable polymers, and the thickness of the coating were tailored to impart various release rates. A relatively steady release rate for over 40 days after an initial burst was achieved using a formulation for long-term release, which is desirable for establishing and maintaining the necessary therapeutic levels. Mathematical models were developed for both in vitro and in vivo drug release into a liquid of limited volume, taking into account a moving boundary of the dispersed drug and a time-dependent boundary condition. A concentration-dependent effective diffusion coefficient was used to count increased porosity as the solid drug had dissolved. The finite element method and computer programs were applied to solve the differential equations and predict the in vitro and in vivo release kinetics. The model prediction agreed well with the in vitro experimental data and provided guidance for designing the device for in vivo release in root canals. The result of in vitro antimicrobial tests, performed using a bovine tooth model, suggested that the device was effective in reducing growth of microbes.

Algorithms↗

PubMed2000

Coupling gravitons to matter.

Using relationships between open and closed strings, we present a construction of tree-level scattering amplitudes for gravitons minimally coupled to matter in terms of gauge theory partial amplitudes. In particular, we present examples of amplitudes with gravitons coupled to vectors or to a single fermion pair. We also present two examples with massive graviton exchange, as would arise in the presence of large compact dimensions. The gauge charges are represented by flavors of dynamical scalars or fermions. This also leads to an unconventional decomposition of color and kinematics in gauge theories.

Astronomy↗

PubMed1999

Customisation of AFLP analysis for cassava varietal identification.

Amplified fragment length polymorphism (AFLP) markers were used in the characterization of eight cassava varieties. This nonradioactive AFLP system was customized in terms of the choice of restriction enzymes used and the selection of nucleotides added to the 3' end of primers. EcoRI/MseI and HindIII/MseI fragments generally gave monomorphic profiles while ApaI/TaqI fragments produced polymorphic profiles suggesting a genome with high G + C content. It was possible to identify the eight cassava varieties used in this study using CTG as selective bases at the TaqI primer. For cassava, the AFLP system provided a higher number of loci detected per run when compared to RAPD. The reliability accompanying AFLP analysis would thus make it suitable for the characterization of cassava varieties.

DNA Fingerprinting↗

PubMed1999

Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome.

It is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response. Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B. Indeed, the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease.

Acetylcysteine↗

PubMed1998

Penetrating pencil injury: an unusual case of child abuse.

OBJECTIVE: We report an unusual case of penetrating pencil injury in a young child that turned out to be a case of physical abuse. METHOD: This is a case report with review of the literature. RESULTS: A 4-year-old boy was brought by his mother to the accident and emergency department for a penetrating wound of the right hand. He was said to have injured himself during a fall at home while holding a sharpened lead pencil. The pencil broke after penetrating the hypothenar eminence, leaving the graphite tip embedded in the palm. On surgical exploration, a piece of graphite measuring 1.3 cm was removed. The injury was actually inflicted by his mother because he failed to complete his homework properly. Deep penetrating injuries associated with the lead pencil are uncommon events in the medical literature. They are often reported as accidental and usually involve the oropharynx and the orbit. CONCLUSION: Deep penetrating injury with a pencil is unusual in childhood and the public should be made aware of the possibility of nonaccidental injury.

Child Abuse↗

PubMed1996

Suppression of prostaglandin H synthase-2 induction in human monocytes by in vitro or in vivo administration of interleukin 4.

IL-4 is a potent modulator of monocyte function. Our previous studies demonstrated that the suppression of monocyte matrix metalloproteinase production by IL-4 is a result of its inhibition of PGE2 synthesis, which was attributed to an effect on prostaglandin synthase. Here we report on the in vitro and in vivo effects of IL-4 on monocyte prostaglandin H synthase-2 (PGHS-2) and its regulation by second messengers. Stimulation of monocytes with either LPS or Con A resulted in the induction of PGHS-2 which was significantly inhibited by IL-4. Inhibition of PGHS-2 mRNA and protein was detected at 0.05 to 0.1 ng/ml of IL-4 with substantial suppression at 10 to 20 ng/ml. If added later than 2 hr after LPS, IL-4 failed to suppress PGHS-2, indicating that IL-4 acted early in the signaling cascade. Moreover, the ability of exogenously added PGE2 or Bt2cAMP to restore PGHS-2 production in IL-4-treated monocytes further suggested early disruption of the pathway. The early event inhibited by IL-4 did not involve suppression of phospholipase activity, because LPS-induced arachidonic acid release was relatively unaffected by IL-4. Unlike PGHS-2, PGHS-1, the constitutively expressed PGHS, was not modulated by IL-4. Thus, IL-4 appears to selectively block PGHS-2 synthesis, thereby blocking subsequent steps in the pathway leading to the production of matrix metalloproteinases. In an extension of these findings, we examined peripheral blood monocytes from cancer patients undergoing IL-4 therapy. In these cells the induction of PGHS-2 expression by LPS was significantly reduced compared to that of monocytes obtained prior to IL-4 therapy. Although perhaps not relevant as an antitumor mechanism, these findings have important implications in defining the potent anti-inflammatory activities of IL-4 in vitro and in vivo.

Amino Acid Sequence↗

PubMed1995

Monocyte-induced cytokine expression in cultured human retinal pigment epithelial cells.

Monocytes and retinal pigment epithelial cells are intimately associated in membranes of eyes with proliferative vitreoretinopathy and in certain types of uveitis. The goal of this study was to determine whether monocytes modulate cytokine expression in retinal pigment epithelial cells, and if so, to identify the monocyte products responsible for this effect. Cultured human retinal pigment epithelial cells were exposed to varying concentrations of monocyte-conditioned medium from unstimulated human monocytes for 1-48 hr, or from monocytes prestimulated with lipopolysaccharide. mRNA expression of interleukin-1 beta, interleukin-6, interleukin-8, melanoma growth stimulating activity/gro alpha and gamma, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain was determined by reverse transcription polymerase chain reaction. Protein secretion of selected cytokines, interleukin-1 beta, interleukin-6, interleukin-8, macrophage colony stimulating factor and transforming growth factor-beta 2 was measured in RPE-conditioned medium by ELISA. Retinal pigment epithelial cells constitutively expressed mRNA for interleukin-6, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain. Interleukin-1 beta, melanoma growth stimulating activity/gro alpha and gamma and interleukin-8 were not expressed under basal conditions. Stimulated monocyte-conditioned medium markedly induced mRNA of all cytokines except basic fibroblast growth factor and transforming growth factor-beta 2 in a dose- and time-dependent manner. Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha. Stimulated monocyte-conditioned medium also induced a time-dependent increase in interleukin-6, Interleukin-8, macrophage colony stimulation factor and transforming growth factor-beta 2, but not interleukin-1 beta protein secretion (p < 0.05 for all time points). Neutralizing antibodies to interleukin-1 beta, or tumour necrosis factor alpha, but not interleukin-1 alpha, significantly reduced cytokine mRNA expression induced by stimulated monocyte-conditioned medium. The combination of all three neutralizing antibodies almost entirely eliminated monocyte-induced mRNA expression and protein production of all cytokines studied. Activated monocytes secrete a heterogeneous mixture of products that together strongly induce expression of multiple cytokines in human retinal pigment epithelial cells. Most if not all of the inducing effect can be accounted for by interleukin-1 beta and tumour necrosis factor alpha. Because cytokines have been implicated in proliferative vitreoretinopathy and uveitis, monocyte-mediated cytokine expression by RPE cells may serve to initiate and perpetuate these diseases.

Antibodies↗