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Biomedical subjects

D T Wong

Publications and source records attributed to D T Wong.

At least 73 records · Page 4Linked to original sources
PubMed1998

Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.

PURPOSE: To report clinical features and surgical management of neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. METHODS: Seven consecutive eyes of seven nondiabetic patients who developed neovascular complications associated with rubeosis iridis and peripheral retinal detachment after scleral buckling and vitrectomy procedures were retrospectively reviewed. None of the eyes had clinical evidence of anterior segment ischemia or retinal vascular disease, but each eye developed rubeosis iridis and neovascular complications. RESULTS: Of the seven eyes with rubeosis iridis and peripheral retinal detachment, six developed recurrent or progressive vitreous hemorrhage, and three developed progressive neovascular glaucoma. Four eyes underwent a revision procedure to repair the peripheral retinal detachment, and anterior proliferative vitreoretinopathy was found in each of these cases. Rubeosis iridis regressed in all three eyes in which surgery resulted in complete reattachment of the retina. In one eye with persistent peripheral retinal detachment and in the three remaining eyes that did not undergo revision surgery, rubeosis iridis persisted and was associated with long-term neovascular complications. Final corrected visual acuity was 20/70 to 20/400 in three eyes with total retinal reattachment and no light perception to hand motions in four eyes with persistent peripheral retinal detachment and rubeosis iridis. CONCLUSION: Visually significant neovascular complications may occur in eyes that develop rubeosis iridis associated with peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. Successful repair of the peripheral retinal detachment may induce regression of rubeosis iridis, reduce associated complications, and improve the long-term prognosis of these eyes.

Adult↗
PubMed1998

Prediction of human oral cancer radiation responsiveness by histone (H3) mRNA in situ hybridization: a preliminary report.

PURPOSE: Cell cycle kinetics are believed to be a key determinant in radiation responsiveness. However, histomorphologic analysis remains an unreliable method of identifying proliferating cells. In this study, the fraction of cells undergoing division within oral cancer biopsy samples was used to predict the responsiveness of the tumor to radiation therapy. PATIENTS AND METHODS: Eighteen cases of T1 or T2 squamous cell carcinoma of the floor of the mouth with known clinical outcomes were identified. All were treated at the Massachusetts General Hospital with external beam radiation therapy alone. The fraction of proliferating cells was determined using in situ hybridization of histone (H3) mRNA expression. Tissue viability and mRNA status was verified using in situ hybridization for beta-actin mRNA expression. RESULTS: Matching the fraction of oral tumor cells positively labeled for histone (H3) mRNA (histone labeling index or HLI) with the actual clinical outcome showed that the HLI of radioresponsive oral tumors (12 cases) was 0.336+/-0.185 (approximately 34%+/-19%), whereas that for radioresistant oral tumors (six cases) was 0.088+/-0.078 (approximately 9%+/-7.8%). Using t-test statistical analysis for unpaired samples showed that the difference in HLI between the two groups was significantly different (P=.0068). CONCLUSIONS: It is concluded that the use of in situ detection of histone (H3) mRNA may be a useful adjunctive criterion in the choice of treatment for human oral cancer.

Adult↗
PubMed1998

Intraoperative awareness in fast-track cardiac anesthesia.

BACKGROUND: Fast-track cardiac anesthesia, using low-dose narcotics combined with short-acting anesthetic and sedative agents, facilitates early tracheal extubation after cardiac surgery. The incidence of awareness with this anesthetic technique has not been investigated previously. The purpose of this study was to prospectively investigate the incidence of intraoperative awareness with explicit memory of events during fast-track cardiac anesthesia. METHODS: Data were collected prospectively over a 4-month period from 617 consecutive adult patients undergoing cardiac surgery at a university hospital. All patients received a fast-track cardiac anesthetic regimen. Patients underwent a structured interview by a research nurse 18 h after extubation. A standard set of questions was asked during this interview to determine if the patient had explicit memory of any event from induction of anesthesia to recovery of consciousness. RESULTS: Nine patients did not complete a postoperative interview because of death (n = 7) or postoperative confusion (n = 2). The last memory before surgery reported in 420 (69.1%) patients was waiting in the holding area at the operating suite, and in the remaining 188 (30.9%) patients it was lying on the operating table before induction of anesthesia. Two patients (0.3%) had explicit memory of intraoperative events. One of the two patients also had explicit memory of pain. Neither patient reported adverse psychological sequelae. CONCLUSIONS: The authors report an incidence of awareness in fast-track cardiac anesthesia of 0.3%. This is the lowest incidence of awareness currently reported during cardiac surgery. This low incidence of awareness may be related to the use of a balanced anesthetic technique involving the continuous administration of volatile (isoflurane) or intravenous (propofol) anesthetic agents before, during, and after cardiopulmonary bypass.

Anesthesia↗
PubMed1998

Hepatitis C virus structural proteins assemble into viruslike particles in insect cells.

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The study of HCV has been hampered by the low level of viral particles in infected individuals, the inability to propagate efficiently the virus in cultured cells, and the lack of a convenient animal model. Due to these obstacles, neither the structure of the virus nor the prerequisites for its assembly have been clearly defined. In this report, we describe a model for the production and purification of HCV-like particles in insect cells using a recombinant baculovirus containing the cDNA of the HCV structural proteins. In insect cells, expressed HCV structural proteins assembled into enveloped viruslike particles (40 to 60 nm in diameter) in large cytoplasmic cisternae, presumably derived from the endoplasmic reticulum. Biophysical characterization of viruslike particles by CsCl and sucrose gradient centrifugation revealed biophysical properties similar to those of putative virions isolated from infected humans. The results suggested that HCV core and envelope proteins without p7 were sufficient for viral particle formation. Analysis of particle-associated nucleic acids demonstrated that HCV RNAs were selectively incorporated into the particles over non-HCV transcripts. The synthesis of HCV-like particles in insect cells may provide an important tool to determine the structural requirements for HCV particle assembly as well as to study viral genome encapsidation and virus-host interactions. The described system may also represent a potential approach toward vaccine development.

Animals↗
PubMed1998

IL-1 beta and IL-6 in mouse parotid acinar cells: characterization of synthesis, storage, and release.

Synthesis, storage, and secretion of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) and the anti-inflammatory cytokine IL-6 have not been established in normal exocrine gland secretory cells. Parotid glands and isolated acinar cells prepared from BALB/c mice were homogenized for RNA isolation and reverse transcription-polymerase chain reaction (RT-PCR). IL-1 beta and IL-6 enzyme-linked immunosorbent assays (ELISAs) were done on supernatants prepared from mouse parotid acinar cell (MPAC) preparations unstimulated or stimulated between 0 and 10 min with 10(-5) M norepinephrine at 37 degrees C. MPACs were fixed in paraformaldehyde, frozen sectioned for light and electron microscopy, and labeled with antibodies to IL-1 beta and IL-6. Mouse specific riboprobes to IL-1 and IL-6 were used for in situ hybridization. RT-PCR yielded the expected IL-1 (336-bp) and IL-6 (614-bp) mRNA products. By ELISA, stimulated MPACs showed a significant increase in IL-1 beta (P < 0.03) and IL-6 (P < 0.01) release into supernatants by 10 min that paralleled the time course of amylase release. In situ hybridization showed the presence of transcripts for IL-1 and IL-6 in glandular epithelial cells. Gold-labeled IL-1 beta and IL-6 were significantly higher (P < 0.01) in granules than in the nucleus and cytoplasm. This study shows that MPACs synthesize IL-1 beta and IL-6 and release these cytokines from their granules after alpha- and beta-adrenergic stimulation.

Amylases↗
PubMed1998

Duloxetine (LY 248686): an inhibitor of serotonin and noradrenaline uptake and an antidepressant drug candidate.

Duloxetine is a potent inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NE) uptake in vitro and in vivo and is 3- to 5-times more effective at inhibiting 5-HT uptake. Duloxetine is a weak inhibitor of dopamine (DA) uptake and the binding of radioligands to neurotransmitter receptors. Upon administration of duloxetine in vivo, the inhibitory effects on uptake of 5-HT and NE persist for up to 8 h. Desmethylduloxetine, a potential metabolite, is also an inhibitor of 5-HT and NE uptake. Consistent with the ability to inhibit the uptake of 5-HT, duloxetine blocks p-chloroamphetamine induced depletion of mouse and rat brain 5-HT. Duloxetine also blocks the 6-hydroxydopamine induced depletion of mouse heart NE and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced depletion of NE in frontal cortex but does not block the MPTP induced depletion of DA in rat striatum. Electrophysiological studies show that duloxetine decreases the activity of 5-HT neurones in dorsal raphe and at a 5-times higher dose also decreases the activity of NE neurones in the locus coeruleus. Microdialysis techniques have demonstrated that duloxetine effectively elevates extracellular 5-HT and NE levels in rat frontal cortex and hypothalamus. Antagonists at somatodendritic 5-HT(1A) autoreceptors or at presynaptic alpha(2)-adrenergic receptors could augment the duloxetine induced elevation of extracellular 5-HT, NE and DA levels. Duloxetine produces behavioural responses consistent with the enhancement of 5-HT and NE neurotransmission. Pharmacokinetic studies in healthy human volunteers show that duloxetine has a half-life of 10 - 15 h without the influence of food. In preliminary clinical trials, duloxetine has shown antidepressive effects in patients with major depression. Duloxetine offers an opportunity to utilise combined central 5-HT and NE neuronal pathways to improve the treatment of patients with major depression.

Journal Article↗
PubMed1998

Carotid endarterectomy and abdominal aoritc aneurysm repair: are these reasonable treatments for patients over age 80?

Due to the aging of America, increased numbers of very elderly patients require peripheral vascular surgery. From April 1980 to November 1997, 191 patients age 80 years or older had carotid endarterectomy (CEA) and/or abdominal aortic aneurysm (AAA) repair at Loma Linda University Medical Center. The total perioperative stroke and death rate in the CEA group was 2.9 per cent. Mean postoperative cumulative survival in this group was 8.4 years. The cumulative stroke-free survival rate was 95.5 per cent for all yearly postoperative intervals up to 12 years. The perioperative mortality rate was 10.7 per cent in the nonruptured AAA group and 53.8 per cent in the ruptured AAA group (P < 0.00001). Mean cumulative survival was 8.6 years in the nonruptured AAA group and 1.1 years in the ruptured AAA group (P = 0.0001). These data support the conclusion that CEA and nonemergent AAA repair in octo- and nonagenarians are safe and effective in prolonging stroke-free and rupture-free survival. The utility of ruptured AAA repair in this age-group is less clear.

Aged↗
PubMed1998

The selective norepinephrine reuptake inhibitor, LY368975, reduces food consumption in animal models of feeding.

The compound, LY368975 ((R)-thionisoxetine) is a potent and selective inhibitor of the norepinephrine (NE) reuptake site. We evaluated the in vivo properties of LY368975 in various animal models. In mice, LY368975 prevented heart NE depletion by 6-hydroxydopamine with an ED50 of 1.22 mg/kg. In rats, orally administered LY368975 inhibited 3H-NE uptake into hypothalamic synaptosomes ex vivo with an ED50 of 2.5 mg/kg and 3H-tomoxetine binding to the NE transporter with an ED50 of 2.7 mg/kg. When rats were deprived of food for 18 hr, 10 mg/kg LY368975 was able to suppress food intake 1, 2 and 4 hr after reintroduction of the feed. In nonfasted rats trained to drink sweetened condensed milk, LY368975 produced a dose-dependent reduction in consumption with a 44% decrease at 3 mg/kg. At doses up to 10 mg/kg p.o., LY368975 produced no significant effects on locomotor activity suggesting the compound does not activate or sedate the animals at pharmacologically relevant doses. Therefore, LY368975 is an orally available and centrally active NE reuptake inhibitor that is capable of reducing food consumption in rodents. Compounds of this class may have use in the treatment of obesity and eating disorders.

Adrenergic Uptake Inhibitors↗
PubMed1997

Greater effects of fluoxetine and its combination with (-)-pindolol in elevating hypothalamic serotonin in rats during dark hours.

Administration of fluoxetine (10 mg/kg i.p.) caused a significantly greater increase in extracellular 5-HT levels in hypothalamus of rats adapted to a reverse light period (lights off 9:00 am-9:00 pm) than those adapted to the regular cycle (lights off 6:00 pm-6:00 am). Sequential administration of the antagonist 5-HT1A/beta-adrenergic receptors (-)-pindolol at 0.1, 0.3, 1, and 3 mg/kg s.c. significantly enhanced the fluoxetine-induced elevation of 5-HT levels in both groups of rats. (-)-Pindolol at 0.1 mg/kg potentiated the fluoxetine-induced elevation in 5-HT levels significantly higher in rats adapted to the reverse light cycle than in those accustomed to the regular light cycle. The greater effects of fluoxetine and the subsequent administration of (-)-pindolol in the reverse cycle group may relate to the difference in activity of 5-HT neurons in the dorsal raphe of conscious animals adapted to the two light periods.

Adrenergic beta-Antagonists↗
PubMed1997

The molecular biology of oral carcinogenesis: toward a tumor progression model.

PURPOSE: An understanding of the molecular basis of oral carcinogenesis will alter our clinical approach to oral cancer. The nomenclature and major themes of molecular oral tumor biology are reviewed, beginning with the regulation events governing normal cellular physiology. In carcinogenesis, chromosomal or cytogenetic alterations lead to deregulation of tightly controlled stimulatory and inhibitory pathways, growth-promoting proto-oncogenes are mutated into overactive oncogenes, and growth-suppressing or tumor suppressor genes are inactivated. Recent advances in defining these fundamental mechanisms of tumor biology may allow prevention, diagnosis, and treatment of oral cancer to be approached at the molecular level.

Anticarcinogenic Agents↗
PubMed1997

Characterization of synthesis and storage of TGF-alpha in rat parotid acinar and intercalated duct cells.

Although the expression and biological role of transforming growth factor-alpha (TGF-alpha) have been explored in a variety of normal cells in mammalian species, little is known about the storage of TGF-alpha in secretory cells of exocrine organs. Parotid glands from four rats were homogenized for RNA isolation followed by reverse transcription-polymerase chain reaction to determine the presence of TGF-alpha message. In situ hybridization using a hamster-specific TGF-alpha riboprobe was done on paraffin sections. Parotid gland and isolated acinar cells were processed for transmission electron microscopy (TEM) and postembedding immunogold labeled for TGF-alpha. Gold particles were counted on approximately 200 granules in 10 acinar cells and in 10 intercalated duct cells. Labeling density was calculated as the number of gold particles per square micrometer +/- SD. Statistical significance was calculated using one-way analysis of variance. Using multiple technologies, we have established that rat parotid acinar and intercalated duct cells synthesize TGF-alpha and store the precursor form of this cytokine in their secretory granules.

Animals↗
PubMed1997

Pharmacology of butylthio[2.2.2] (LY297802/NNC11-1053): a novel analgesic with mixed muscarinic receptor agonist and antagonist activity.

Butylthio[2.2.2], ((+)-(S)-3-(4-butylthio-1,2,5-thiadiazol-3-yl)-1-azabicyclo[2.2.2] octane; LY297802/NNC11-1053) is a muscarinic receptor ligand which is equiefficacious to morphine in producing antinociception. In vitro, butylthio[2.2.2] had high affinity for muscarinic receptors in brain homogenates, but had substantially less or no affinity for several other neurotransmiter receptors and uptake sites. In isolated tissues, butylthio[2.2.2] was an agonist with high affinity for M1 receptors in the rabbit vas deferens (IC50 = 0.33 nM), but it was an antagonist at M2 receptors in guinea pig atria (pA2 = 6.9) and at M3 receptors in guinea pig urinary bladder (pA2 = 7.4) and a weak partial agonist in guinea pig ileum, which contains a heterogeneous population of muscarinic receptors. In vivo, butylthio[2.2.2] was without effect on acetylcholine, dopamine and serotonin levels in rat brain. Moreover, butylthio[2.2.2] did not decrease charcoal meal transit in mice, nor did it significantly alter heart rate in rats. Further, butylthio[2.2.2] did not produce parasympathomimetic effects such as salivation or tremor in mice, but it antagonized salivation and tremor produced by the nonselective muscarinic agonist oxotremorine. The present data demonstrate that butylthio[2.2.2] is a novel muscarinic receptor mixed agonist/antagonist and its pharmacological profile suggests that it may have clinical utility in the management of pain as an alternative to opioids.

Analgesics↗
PubMed1997

In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug.

BACKGROUND: Classical (typical) antipsychotic drugs are in wide use clinically, but some patients do not respond at all to treatment, while in others, negative symptoms and cognitive deficits fail to respond. Also, these drugs often cause serious motor disturbances. Clozapine, an atypical antipsychotic, appears to correct many of these deficiencies, but has a significant incidence of potentially fatal agranulocytosis. Accordingly, we attempted to develop a prototype of a new generation of antipsychotics that is both more efficacious and safe. Our strategy was to create a compound that is not only active in behavioral tests that predict antipsychotic action but also shares the rich, multifaceted receptor pharmacology of clozapine without its side effects. To this end, Eli Lilly and Co. developed olanzapine. In this article we characterize the in vitro and in vivo receptor pharmacology of olanzapine. METHOD: We evaluated olanzapine interactions with neuronal receptors using standard assays of radioreceptor binding in vitro and well-established in vivo (functional) assays. RESULTS: Binding studies showed that olanzapine interacts with key receptors of interest in schizophrenia, having a nanomolar affinity for dopaminergic, serotonergic, alpha 1-adrenergic, and muscarinic receptors. In vivo olanzapine is a potent antagonist at DA receptors (DOPAC levels; pergolide-stimulated increases in plasma corticosterone) and 5-HT receptors (quipazine-stimulated increases in corticosterone), but is weaker at alpha-adrenergic and muscarinic receptors. Olanzapine has little or no effect at other receptors, enzymes, or key proteins in neuronal function. Olanzapine has a receptor profile that is similar to that of clozapine: it is relatively nonselective at dopamine receptor subtypes and it shows selectivity for mesolimbic and mesocortical over striatal dopamine tracts (electrophysiology; Fos). CONCLUSION: The binding and functional profile of olanzapine (1) is similar to that of clozapine, (2) indicates that olanzapine is an atypical antipsychotic drug, and (3) is consistent with clinical efficacy. If olanzapine also proves to be safe, then it will have high potential to become a more ideal antipsychotic drug.

Animals↗
PubMed1997

Depletion of eosinophil infiltration by anti-IL-5 monoclonal antibody (TRFK-5) accelerates open skin wound epithelial closure.

Wound healing is critical to the survival of the species after injury. Using hamsters as an experimental model, we have shown that eosinophils infiltrate prominently into skin wounds and that they express transforming growth factor-alpha and -beta 1 mRNAs and proteins. We hypothesized that eosinophils are important in wound healing. As no animal model is genetically deficient in eosinophils, a suitable way to test the hypothesis is to selectively reduce and/or deplete the influx of eosinophils into the wound sites. In this study, we report that anti-interleukin-5 monoclonal antibody (TRFK-5) treatment can deplete eosinophils in cutaneous healing wounds. We found that wound closure by re-epithelialization in the experimental group was 4 days faster than in the control group (P < 0.01). The density of eosinophils in day-9 wounds was significantly lower in the experimental group (P < 0.01). Wound-associated eosinophils in each of the TRFK-5-treated hamsters were depleted to the level comparable to unwounded hamster skin. These results demonstrate that anti-interleukin-5 monoclonal antibody treatment can effectively decrease eosinophil infiltration into hamster cutaneous healing wounds and indicate a role for eosinophils in negatively affecting wound re-epithelialization.

Animals↗
PubMed1997

Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment.

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.

Adult↗
PubMed1996

Human eosinophils elaborate the lymphocyte chemoattractants. IL-16 (lymphocyte chemoattractant factor) and RANTES.

Eosinophils and CD4+ lymphocytes are preferentially recruited into sites of allergic inflammation. A role for eosinophils in the recruitment of CD4+ lymphocytes has not been defined. We studied the capacity of human eosinophils to release chemoattractants for T lymphocytes. Supernatants of cultured eosinophils contained chemoattractant activity for lymphocytes, which was predominantly due to IL-16 (lymphocyte chemoattractant factor) and RANTES. With neutralizing Abs, eosinophil-derived lymphocyte chemotactic activity was diminished by a mean (+/- SEM) of 60 +/- 3% with polygonal anti-IL-16 Ab, 69 +/- 4% with anti-IL-16 mAb, 48 +/- 3% with anti-CD4 F(ab) (IL-16 receptor blockade), 40 +/- 4% with anti-RANTES mAb, and 88 +/- 5% with a combination of anti-IL-16 and anti-RANTES mAbs. IL-16 and RANTES were detectable in eosinophil-derived supernatants by ELISA. Eosinophils constitutively expressed mRNA transcripts for both IL-16 and RANTES detectable by reverse transcription-PCR and contained preformed IL-16 and RANTES demonstrable by ELISA of cell lysates and by immunocytochemistry of freshly isolated eosinophils. Thus, eosinophils are a source of two cytokines, IL-16 and RANTES, that are chemoattractants for lymphocytes as well as eosinophils. These data indicate that eosinophils could contribute cytokines to enhance the recruitment of additional populations of CD4+ lymphocytes and eosinophils.

Antibodies, Monoclonal↗