Biomedical subjects

G M Wang

Publications and source records attributed to G M Wang.

At least 19 recordsLinked to original sources

PubMed2002

Experimental demonstration of violations of the second law of thermodynamics for small systems and short time scales.

We experimentally demonstrate the fluctuation theorem, which predicts appreciable and measurable violations of the second law of thermodynamics for small systems over short time scales, by following the trajectory of a colloidal particle captured in an optical trap that is translated relative to surrounding water molecules. From each particle trajectory, we calculate the entropy production/consumption over the duration of the trajectory and determine the fraction of second law-defying trajectories. Our results show entropy consumption can occur over colloidal length and time scales.

Journal Article↗

PubMed2001

Structural alterations of sugar chains in urine fibronectin from bladder cancer patients and its enzymatic mechanism.

PURPOSE: To study the structural alterations of asparagine-linked sugar chains (N-glycans) on urine fibronectin (Fn) from bladder cancer (BCa) patients and its enzymatic mechanism. METHODS: Eight pairs of urine samples from eight BCa patients pre-operation and 3 months post-operation (which proved to be normal) were collected, and the Fn in the urine samples was purified with an anti-Fn antibody affinity column. Different lectins labeled with horseradish peroxidase (HRP) were used as probes to bind the glycans of purified Fn immobilized on membrane. Enhanced chemiluminescence (ECL) reagent was adopted to estimate the activity of the bound HRP as a measure of the binding affinity of the Fn glycans to lectins, and expressed as luminescent light units (LLU). The enzymatic mechanism of the structural alteration of N-glycans in BCa Fn was studied by determination of GnT activities using the HPLC method and fluorescent-labeled substrate. RESULTS: The mean LLU of BCa Fn was only 18.1% of the normal samples when Con A-HRP were used as probes, while the mean LLU of the BCa group was 3.34 times and 3.26 times higher than normal for the DSA-HRP and WGA-HRP probes, respectively. The individual data of the patients did not overlap between the BCa sample and normal counterparts, indicating that the positive rates were 100%, regardless of which lectin-HRP was used. These results reveal that the antennary number and bisecting GlcNAc structure are increased in the N-glycans of urine Fn from BCa assessed according to the binding specificity of ConA, DSA, and WGA. In addition, the binding affinities of urine Fn with DSA and WGA were correlated to pathological stage, and the affinity of Fn with WGA was also correlated with pathological grade. The results of GnT determination showed that GnT-III, IV, and V in BCa tissues increased by 34.0, 18.1, and 1.6 times, respectively, in normal bladder tissues which were at least 5 cm away from the BCa of the same bladder. These findings were compatible with the structural changes of N-glycans in BCa Fn, since GnT-III and GnT-IV/V are responsible for the synthesis of bisecting GlcNAc and the increase of antennary number in N-glycans, respectively. CONCLUSIONS: (1) The highest elevation of GnT-III and the close relationship between the WGA binding of BCa Fn with the pathological stage and grade of BCa indicate that the increase of bisecting GlcNAc in N-linked glycans contributes more to the malignant behavior of BCa than the increase of GnT-IV, GnT-V, and the antennary number. (2) The correlation of altered activities of bladder GnTs with the abnormal structures of urine Fn in BCa patients indicates that the urine Fn is synthesized in the bladder. (3) The lectin-HRP assay for analyzing the structure of N-glycans in urine Fn may be used as a simple and accurate diagnosis method for BCa in the future.

Adult↗

PubMed2000

Norepinephrine uptake sites in the locus coeruleus of rat lines selectively bred for high and low alcohol preference: a quantitative autoradiographic binding study using [3H]-tomoxetine.

BACKGROUND: The locus coeruleus (LC) is the largest norepinephrinergic cell group in the central nervous system and contains a high density of norepinephrine (NE) uptake sites. Alcohol-preferring (AP) rats and high-alcohol-drinking (HAD) rats are selectively bred for high alcohol preference, whereas alcohol-nonpreferring (NP) rats and low-alcohol-drinking (LAD) rats are bred for low alcohol preference. However, it is unknown whether NE uptake sites in the LC are associated with alcohol preference in AP and HAD rats when compared with their respective control rats, NP and LAD rats. This study was designed to examine this question. METHODS: Animals were decapitated and brains were removed, frozen with dry ice powder, and stored in a deep freezer. The LC tissue blocks were cut into 14 micro cryostat sections, collected on glass slides, and incubated with 0.6 nM [3H]-tomoxetine in 50 mM Tris-HCl buffer system. For nonspecific binding, 1 microM desipramine was added to the radioactive ligand. Sections were rinsed, quickly dried, and processed for quantitative autoradiography. In addition, galanin content in the LC was also studied. RESULTS: The LC possessed a high density of [3H]-tomoxetine binding sites. There were fewer tomoxetine binding sites (fmol/mg protein) in the AP rats (433.0 +/- 8.1) than in the NP rats (495.6 +/- 3.7). HAD rats (386.5 +/- 13.2) also possessed fewer tomoxetine binding sites than LAD rats (458.7 +/- 10.1). Galanin content in the LC was similar between AP and NP rats and between HAD and LAD rats. CONCLUSIONS: Because both AP rats and HAD rats were selectively bred for alcohol preference, the finding of consistently low levels of [3H]-tomoxetine binding in the LC of these two lines of rats with high alcohol preference suggests that down-regulation of NE transporters in the LC of AP and HAD rats may be associated with alcohol-seeking behavior. A possible involvement of the coerulear NE uptake sites in depression is also discussed. Galanin in the LC may not relate to alcohol preference.

Alcohol Drinking↗

PubMed1999

Diffusive mobility of fractal aggregates over the entire Knudsen number range.

We determine the effective mobility radius for fractal aggregate particles. Our method is to use static light scattering to measure the radius of gyration R(g) of the aggregates, and dynamic light scattering to measure the diffusion coefficient hence the mobility radius R(m). The range of our results can be specified by the Knudsen number Kn, which is the mean free path of the medium molecules divided by the radius of the aggregate. Our results apply to the entire range of Kn from the continuum limit (Kn=0) to the free molecular limit (Kn>>1). In the continuum regime we find R(m)/R(g)=0.97+/-0.05 when the aggregate fractal dimension is D(f) approximately 2.15, and 0.70+/-0.05 when D(f) approximately 1.75. The latter result is independent of Kn for Kn < or approximately 1.3. The free molecular mobility goes as R(m)=aN(0.44+/-0.03), where a is the monomer radius and N is the number of monomers per aggregate. Since R(g) approximately aN(1/D(f)), R(m)/R(g) is not a constant when Kn is large. We find for all Kn that the functionality of R(m)/R(g) must always begin with the correct N-->1 limit, and this affects experimental observation.

Journal Article↗

PubMed1999

Size distribution effect on the power law regime of the structure factor of fractal aggregates.

We consider the large qR(g), where q is the magnitude of the scattering wave vector and R(g) is the aggregate radius of gyration, part of the structure factor of fractal aggregates, and quantify the coefficient C of the power law, S(q) approximately C(qR(g))(-D), where D is the fractal dimension, for various structure factors proposed in the literature. With the aid of earlier work, we conclude the most accurate structure factors have C=1.0. We then calculate the effects of polydispersity on this coefficient, and show the effects are significant, enough so to allow a measurement of the distribution width. These concepts are accurately supported with scattering data from a diffusion limited aerosol and a reaction limited colloid.

Journal Article↗

PubMed1999

Perinatal hypoxia-ischemia decreased neuronal but increased cerebral vascular endothelial IGFBP3 expression.

In adults, insulin-like growth factor binding protein 3 (IGFBP3) is the main carrier protein for circulating insulin-like growth factors (IGFs) (IGF-I and -II). While most IGFBP3 is synthesized in the liver, it is also expressed locally by many cell types including vascular endothelial cells. The regulation of this endothelial IGFBP3 expression, especially in response to hypoxic-ischemic injury, has not been investigated in vivo. Using in situ hybridization histochemistry, we studied the cellular distribution of IGFBP3 mRNA in rat brains following hypoxic-ischemic injury at 1, 5, 24, and 72 h of recovery. In normal P7 rat brain, IGFBP3 mRNA was found in neurons within the thalamus, hippocampus, and amygdaloid. Low levels of IGFBP3 mRNA were also detected in cerebral vascular endothelial cells. After the hypoxic-ischemic injury, the levels of neuronal IGFBP3 mRNA substantially decreased within 24 h in areas that were normally supplied by the middle cerebral artery. In the meantime, there was an immediate increase in IGFBP3 expression in vascular endothelial cells throughout the affected hemisphere. This vascular IGFBP3 expression was further enhanced with the highest level at 24 h of recovery whereas neuronal IGFBP3 expression was further decreased. By 72 h of recovery, IGFBP3 was no longer expressed in vascular endothelial cells. Taken together, the activation of IGFBP3 is a likely mechanism by which vascular endothelial cells respond to hypoxic-ischemic insult. In addition, increased endothelial IGFBP3 may modulate the interaction of IGFs with IGF-I receptors at the site of injury and/or act independently on endothelial cell growth.

Animals↗

PubMed1999

Clinical decision making using teleradiology in urology.

OBJECTIVE: Using a personal computer-based teleradiology system, we compared accuracy, confidence, and diagnostic ability in the interpretation of digitized radiographs to determine if teleradiology-imported studies convey sufficient information to make relevant clinical decisions involving urology. Variables of diagnostic accuracy, confidence, image quality, interpretation, and the impact of clinical decisions made after viewing digitized radiographs were compared with those of original radiographs. MATERIALS AND METHODS: We evaluated 956 radiographs that included 94 IV pyelograms, four voiding cystourethrograms, and two nephrostograms. The radiographs were digitized and transferred over an Ethernet network to a remote personal computer-based viewing station. The digitized images were viewed by urologists and graded according to confidence in making a diagnosis, image quality, diagnostic difficulty, clinical management based on the image itself, and brief patient history. The hard-copy radiographs were then interpreted immediately afterward, and diagnostic decisions were reassessed. All analog radiographs were reviewed by an attending radiologist. RESULTS: Ninety-seven percent of the decisions made from the digitized radiographs did not change after reviewing conventional radiographs of the same case. When comparing the variables of clinical confidence, quality of the film on the teleradiology system versus analog films, and diagnostic difficulty, we found no statistical difference (p > .05) between the two techniques. Overall accuracy in interpreting the digitized images on the teleradiology system was 88% by urologists compared with that of the attending radiologist's interpretation of the analog radiographs. However, urologists detected findings on five (5%) analog radiographs that had been previously unreported by the radiologist. CONCLUSION: Viewing radiographs transmitted to a personal computer-based viewing station is an appropriate means of reviewing films with sufficient quality on which to base clinical decisions. Our focus was whether decisions made after viewing the transmitted radiographs would change after viewing the hard-copy images of the same case. In 97% of the cases, the decision did not change. In those cases in which management was altered, recommendation of further imaging studies was the most common factor.

Decision Making↗

PubMed1999

Clinical experience with endoscopic stents for treatment of common bile duct stones.

Endoscopic removal of common bile duct (CBD) stones after endoscopic sphincterotomy (EST) is now a widely accepted procedure. Surgery is usually recommended when extraction of stones after EST fails. For patients with major medical problems or who are at high surgical risk, however, endoscopic stent placement may help to prevent stone impaction and cholangitis. In this report, we describe the long-term effects and complications of biliary stent use in elderly patients with CBD stones. From August 1995 to June 1998, 19 patients with CBD stones underwent stent placement by duodenoscopy. Three of these patients underwent this procedure for temporary treatment while awaiting surgery or EST. In the remaining 16 patients (6 men and 10 women, mean age 76 +/- 10 years), invasive management carried a high risk of complications. We used a 7F straight stent for the first patient, while the remaining 15 received 7F pigtail stents. During a mean follow-up period of 34 months, two patients were lost to follow-up and two patients had migration of the stents. Three patients had acute cholangitis with stents in situ. Of these, one underwent stent exchange 8 months later, while the CBD stones were cleared either by endoscopy or surgery in the other two patients. Five patients died of nonbiliary diseases during the follow-up period. Our results show that long-term biliary stent placement is an advisable alternative therapeutic modality for high-risk and debilitated patients with CBD stones.

Aged↗

PubMed1998

Thioltransferase is present in the lens epithelial cells as a highly oxidative stress-resistant enzyme.

The redox homeostasis is controlled by several enzyme systems. Sulfhydryl groups in lens proteins are very sensitive to oxidative stress and can easily conjugate with nonprotein thiols (S-thiolation) to form protein-thiol mixed disulfides. We have observed an elevation of protein S-S-glutathione (PSSG) and protein-S-S-cysteine (PSSC) in cataractous lenses from humans and from animal models subjected to oxidative stress. We also observed that these protein-thiol mixed disulfides could be spontaneously dissociated and lowered to basal levels if the lens which was pre-exposed to H2O2 was subsequently cultured in H2O2-free medium. This suggests that the lens has a system to repair oxidative damage through dethiolation thereby restoring its redox homeostasis. In other tissues, an enzyme, thioltransferase (TTase), has been shown to be responsible for thiol/disulfide regulation. We recently demonstrated the presence of this enzyme in the lens and in cultured lens epithelial cells. Here, we investigated the response of TTase to H2O2 stress and its possible repair function in cultured lens epithelial cells. Rabbit lens epithelial cell line N/N 1003A was raised to confluence, trypsinized and plated at 0.8 million cells per 60 mm culture dish. The cells were incubated overnight in Eagle's minimum essential medium (MEM) with 1% rabbit serum and then in serum-free MEM for 30 min before a bolus of 0.5 mm H2O2 was added. At intervals of 5, 15, 30 min and up to 3 hr, the cells were harvested and used for enzyme assays for TTase, glutathione reductase (GR), glutathione peroxidase (GPx) and glyceraldehyde-3-phosphate dehydrogenase (G-3PD). Free GSH, total SH and PSSG and PSSC were also determined. Hydrogen peroxide in the medium was measured at each time point. Cells incubated without H2O2 were used as controls. The results showed that the H2O2 concentration was reduced to 50% within 30 min and was undetectable at 2 hr. Cellular GSH dropped to 40% within 5 min and stayed at this level before it began to increase at 90 min and completely recovered by 2 hr. The total SH groups were similar to free GSH. PSSG and PSSC increased 6.5 and 2 times respectively before 30 min and then decreased when GSH started to recover. G-3PD was most sensitive to H2O2 and lost 95% activity within 5 min. The activity was regained quickly when H2O2 diminished in the medium. A similar but less severe pattern was observed in both GPx (60% loss at 60 min) and GR (30% loss at 90 min). In contrast, TTase activity remained constant during the entire 3 hr. Only when a higher dose of H2O2 (0.8-1.0 mM) was used, did TTase activity show a brief loss (<30% at 60 min) and a swift recovery. Cells exposed to H2O2 exhibited a normal morphology with no evidence of DNA fragmentation. The lens epithelial cells showed a remarkable ability to repair the early damages induced by H2O2. The unusual oxidative stress-resistant property displayed by TTase, coupled with its known function suggest that it plays an important role in the repair of oxidative damage.

Animals↗

PubMed1998

Distribution of thioltransferase (glutaredoxin) in ocular tissues.

PURPOSE: A new redox regulating enzyme, thioltransferase (TTase), has been found in the lens. The authors investigated whether TTase is also present in other ocular tissues. METHODS: Fresh enucleated bovine eyes were obtained from a local abattoir 4 hours after death. The eyes were processed immediately to remove corneal epithelial cells, conjunctiva, corneal endothelial cells, iris, ciliary body, lens epithelial cells, vitreous body, and retina. Other than conjunctiva and vitreous body, which were collected from a single eye, all other tissues were pooled from three bovine eyes. Each sample was homogenized in 0.1 M phosphate buffer, pH 7.4, and centrifuged at 10,000 g for 20 minutes, and the supernatant was assayed for TTase activity. Total RNA from each tissue sample was extracted and used for slot blot hybridization using cDNA from pig liver TTase with beta-actin as control. RESULTS: Among all the ocular tissues tested, iris showed the highest TTase activity (35 mU/mg protein) followed by conjunctiva, corneal epithelial cells, and corneal endothelial cells. Ciliary body, lens epithelial cells, and retina had moderate activity. No activity could be detected in vitreous body. The presence of this enzyme transcript in these ocular tissues was further confirmed by the positive slot blot hybridization with the pig liver TTase cDNA. Here again, iris showed the highest TTase mRNA expression, followed by ciliary body, lens epithelial cells, corneal endothelial cells, conjunctiva, retina, and corneal epithelial cells. The whole lens showed the lowest TTase mRNA expression, and no TTase mRNA was found in the vitreous body. CONCLUSIONS: TTase was found in most ocular tissues and was concentrated in the anterior segment of the eye. Highest activity was found in the iris, conjunctiva, corneal epithelial, and endothelial cells. TTase was absent in the vitreous body.

Animals↗

PubMed1997

Relationship of protein-glutathione mixed disulfide and thioltransferase in H2O2-induced cataract in cultured pig lens.

It has been previously shown in H2O2-induced cataract model in the rat lens that protein-GSH (PSSG) formation precedes protein-protein disulfide (PSSP) conjugation and lens opacity. This elevated PSSG spontaneously reduces to a normal level when H2O2 is removed. To verify if thioltransferase (TTase), an enzyme that is known in other tissues to dethiolate PSSG, takes part in this recovery process, we examined the relationship of PSSG and TTase in this cataract model. To ensure enough tissue would be available for various biochemical studies, H2O2 induced cataract in pig lens was established and validated with the rat lens model. The study was divided into two parts. One part was to examine the effect of H2O2 concentration, ranging from 0.1 mM-10 mM, during 24 hr. Another part was to study the H2O2 (1.5 mM) induced cataract progression and recovery, parallel to the long-term study in rat lenses reported previously. These lenses were compared for transparency, wet weight, GSH, PSSG levels and the activity of two redox regulating enzymes, glutathione reductase (GR) and TTase. For the most part, pig lens responded to oxidation parallel to the rat lens except that a higher concentration of H2O2 was needed to achieve the same results. Damage induced by H2O3 was concentration dependent. In general TTase activity and GSH level were depleted with a concomitant increase in PSSG. The D50 (50% damage) for GSH in pig lens was 1.5 mM H2O2 (0.5 mM for rat lens) which was chosen for further studies in cataract progression and recovery. At 1.5 mM H2O2, pig lens showed superficial opacity within 24 hr and deeper cortical opacity in 48 hr. The pre-exposed lens became less cloudy when H2O3 was removed from the medium. Incubation of the lens in 1.5 mM H2O2 for one day also induced 50% GSH depletion and four fold PSSG elevations. This accumulated PSSG was dethiolated spontaneously in the absence of H2O2, similar to the findings in the rat lens and human lens models. In contrast protein-cysteine (PSSC) showed little change and did not respond to the recovery condition. TTase lost 50% activity in these lenses during 24-hr H2O3 exposure but regained most of it under recovery. The study on rat lens showed similar results as before, therefore only data on the relationship of TTase activity to PSSG level during cataract development and recovery is reported here. It was found that in the H2O2 (0.5 mM)-exposed rat lenses, the TTase activity was depleted but PSSG accumulation was accelerated within 8 hr. Both recovered quickly (within 8 hr) as soon as the oxidant was removed. Therefore, protein thiolation and dethiolation processes in the cultured rat or pig lenses display a mirror image with the activity pattern of TTase. Based on the close relationship between lens TTase and PSSG indicated above, it is speculated that TTase may regulate PSSG and maintain it at a low concentration in situ. This repair process may contribute to the improved transparency during recovery. Further studies are planned to substantiate this hypothesis.

Animals↗

PubMed1996

Coordinate IGF-I and IGFBP5 gene expression in perinatal rat brain after hypoxia-ischemia.

Insulin-like growth factor I (IGF-I) is an anabolic pleiotrophic factor essential for postnatal rat brain development, especially during the first 21 days, the "critical growth period." Cerebral hypoxic-ischemic insults occurring during the perinatal period can result in neuronal necrosis and permanent brain damage. To understand the regulation of the action of IGF-I in response to such a metabolic insult, we investigated the gene expression of IGF-I, type I IGF receptor, IGF binding protein (IGFBP)2, and IGFBP5 during the first 72 h after hypoxia-ischemia in the immature rat. At 1 h of recovery, messenger RNA (mRNA) levels of all IGF system components were decreased throughout the hemisphere ipsilateral to the carotid artery ligation. This decrease is more pronounced at 24 h of recovery, especially in areas vulnerable to hypoxic-ischemic injury, such as the thalamus and hippocampus. At 72 h of recovery, although IGFBP2 and type 1 IGF receptor mRNA levels remain suppressed, gene expression of both IGF-I and IGFBP5 was activated in reactive astrocytes.Therefore, during the critical growth period in rats, the transcriptional levels of all IGF system components are extremely sensitive to metabolic perturbations associated with cerebral hypoxia-ischemia. The immediate decrease in IGF-I gene expression may be partially responsible for the impending neuronal death and selective vulnerability of myelinogenesis during the perinatal period.

Animals↗

PubMed1995

Altered IGFBP5 gene expression in the cerebellar external germinal layer of weaver mutant mice.

The IGF system components play important roles in cerebellar development as demonstrated by their specific spatial-temporal expression. IGF-I, type I IGF receptor (IGFR-I), IGFBP2 and IGFBP5 mRNA are localized in distinct cell populations, and all are expressed at the highest levels at the peak of Purkinje cell growth, active synaptogenesis and dendritic formation. To understand IGF-I's action at the cellular level, in situ hybridization was employed to investigate the distribution of IGF system gene transcripts in the cerebellum of weaver mutant mice (wv/wv). Although located ectopically, the surviving Purkinje cells express IGF-I mRNA at the same level in wv/wv as in +/+. No alteration in the cellular distribution or mRNA levels was observed with IGFBP2, or IGFR-I mRNAs. However, the pattern of IGFBP5 expression is altered in the external germinal layer of wv/wv mice. Not only is IGFBP5 expressed by more granule cell precursors of wv/wv cerebellum, but its mRNA level is 2.3 fold that of +/+. The altered IGFBP5 gene expression in granule cell precursors may modulate the interaction of IGF-I with IGFR-I in ways that contribute to their massive death occurring in the development of wv/wv cerebellum.

Animals↗

PubMed1995

A brief photochemically induced oxidative insult causes irreversible lens damage and cataract. I. Transparency and epithelial cell layer.

Short-term photochemical insult of cultured rat lenses caused by the generation of H2O2, O2<--and OH. was found to lead to rapid irreversible damage to the epithelial cell layer. This irreversible damage was measured by Trypan blue staining, terminal deoxyribonucleotidyl transferase labeling, DNA laddering and morphological analyses. There appears to be an inverse relationship between the period of photochemical insult and the post-insult time required to observe epithelial cell damage. Insulting periods of a few hours require post-insult intervals of days to observe significant cell damage and weeks before complete cortical cataracts are found. Epithelial cell damage precedes the loss of transparency.

Animals↗

PubMed1995

A brief photochemically induced oxidative insult causes irreversible lens damage and cataract. II. Mechanism of action.

Using photochemically induced oxidative stress and rat lenses in organ culture with 4% O2 and 4 microM riboflavin, it has been found that the observed changes in lens parameters are, in most cases, irreversible. This has made possible the elucidation of the sequence of biological changes leading to cataract. The earliest detectable changes in lens cell biology are observed in the epithelial cell redox set point and at the DNA level in terms of DNA integrity and 3H-thymidine incorporation followed by decreased membrane transport and changes in gene expression. Significant modification in classical cataract parameters such as hydration, steady state non-protein thiol, glyceraldehyde-phosphate-dehydrogenase activity and transparency occur at later times. The data suggest a definitive pattern of lens breakdown resulting in opacity starting at the epithelial cell level and leading to subsequent fibre cell involvement.

Animals↗

PubMed1995

Calcimycin-induced lens epithelial cell apoptosis contributes to cataract formation.

Previous studies have shown that calcimycin induces cataract in organ culture. To investigate the mechanism of this induction, the viability of lens epithelial cells in calcimycin (calcium ionophore, A23187)-treated rat lenses were examined. During incubation of lenses with 5 microM calcimycin, apoptotic epithelial cells were found after a 2-hr treatment as determined by terminal deoxynucleotidyl transferase (TdT) labeling. The percentage of apoptotic cells quickly rose as the incubation time increased. After a 12-hr incubation, more than 60% of the lens epithelial cells underwent apoptosis. Prolonged c-fos expression, previously shown to be an indicator of programmed cell death, was also observed during this treatment. DNA fragmentation assays further confirmed that the TdT labeled cells were indeed apoptotic. Under the same incubation conditions, the cultured lenses gradually lost transparency and became completely opaque in about 30 hr. Since the vertebrate lens contains only a single layer of epithelial cells, apoptotic death of these cells activated by calcimycin quickly destroys the lens epithelium, impairs homeostasis of the underlying fiber cells and initiates development of lens opacification.

Animals↗

PubMed1995

Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals.

Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation.

Adult↗

PubMed1994

Galanin-containing neurons in the solitary nucleus and locus coeruleus of spontaneously hypertensive rats are associated with genetic hypertension.

Spontaneously hypertensive (SHR) rats contained more galanin (GAL) content and GAL mRNA in locus coeruleus (LC) at the prehypertensive, but not at the well-established hypertensive stage, than did age-matched Wistar-Kyoto (WKY) rats. However, there was also more GAL content, but not GAL mRNA, in the nucleus tractus solitarii (NTS) of SHR rats than WKY rats at both stages. This study suggests that galaninergic neurons in the LC and NTS may participate in the pathogenesis of genetic hypertension.

Animals↗