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Biomedical subjects

V Li

Publications and source records attributed to V Li.

At least 19 recordsLinked to original sources
PubMed2001

Activation of the Ah receptor signaling pathway by prostaglandins.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a diverse range of chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Although no endogenous physiological ligand for the AhR has yet been described, numerous studies support the existence of such a ligand(s). Here we have examined the ability of prostaglandins and related chemicals to activate the AhR signaling system. Using two AhR-based bioassay systems we report that relatively high concentrations of several prostaglandins (namely, PGB3, PGD3, PGF3alpha, PGG2, PGH1, and PGH2) can not only stimulate AhR transformation and DNA binding in vitro, but also induce AhR-dependent reporter gene expression in mouse hepatoma cells in culture. PGG2 also induced AhR-dependent reporter gene expression to a level three-to four fold greater than that observed with a maximal inducing dose of TCDD. Sucrose gradient ligand binding analysis revealed that PGG2 could competitively displace [3H]TCDD from the AhR. Overall, our results demonstrate that selected prostaglandins are weak agonists for the AhR and they represent a structurally distinct and novel class of activator of the AhR signal transduction pathway.

Animals↗
PubMed2001

Cranial birth injuries in term newborn infants.

While cranial birth injuries in term infants are well recognized, to date, only small case series have been described. In an attempt to further define the spectrum of cranial birth injuries, we analyzed 41 consecutive cranial birth injuries at our institution over the period 1991-1998. The most common clinical presentations were apnea (39%) and seizures (37%). Average Apgar scores were 5.7 at 1 min and 7.3 at 5 min; 54% of infants had abnormally low Apgar scores at 1 min and 31% had abnormally low scores at 5 min. The most common intracranial lesion was subdural hemorrhage, present in 73% of infants; most had either a tentorial (57%) and/or interhemispheric (50%) location. Operative treatment was required in 5 infants (12%). Two of the 41 infants (4.8%) died. The study group was compared with a control group of 63 randomly selected births without cranial injury. Using a stepwise logistic regression model, independently significant variables included neonatal birth weight, Apgar scores at 1 and 5 min and mode of delivery. Compared with the controls, the study group had a significantly higher incidence of forceps and/or vacuum deliveries. Combining vacuum, forceps and urgent cesarean section deliveries together as 'urgent' and elective cesarean and spontaneous vaginal deliveries as 'nonurgent', we could find no significant differences between these two groups. Our data conflict with those of Towner et al. [N Engl J Med 1999;341:1709-1714], and suggest that the method of assisted delivery, rather than the urgency of the delivery or dysfunctional labor per se, is a more important variable in cranial birth injuries.

Apgar Score↗
PubMed2001

Use of a craniofacial miniplate for internal fixation in a young child with cervical instability. Case report.

Commercially available anterior cervical internal fixation devices are designed for placement in adults and older children. Use of these systems in preschool-aged children is precluded due to the small size of their cervical vertebral bodies (VBs). The authors describe a 2-year-old boy who suffered a C3-4 injury, resulting in complete ligamentous disruption. Because of the gross cervical instability, they elected to perform surgery via posterior and anterior approaches, supplemented with internal fixation, during the same operation. The purpose of the anterior internal fixation device is to deliver compressive forces onto the interbody graft and keep it in place, thus optimizing the potential for a successful fusion. Because of the discrepancy in size between the VBs and the plate and screws, however, the authors were unable to use any of the standard anterior cervical fixation devices. Instead, they implanted a craniofacial miniplate, and the patient was required to wear an external halo brace. The miniplate provided enough stability to allow for a solid fusion. The authors believe that this technique is a reasonable option in young children who require anterior cervical fixation.

Adult↗
PubMed2000

Involvement of Ets transcription factors and targets in osteoblast differentiation and matrix mineralization.

The osteoblast-like MC3T3-E1 cell line provides an excellent in vitro model of bone development. This system undergoes three orderly time-dependent phases characterized by proliferating preosteoblasts, matrix accumulation by postmitotic differentiating osteoblasts, and mineralization of the matrix, which results in the formation of multilayered bone nodules. The Ets family transcription factors regulate genetic programs that affect the proliferation and differentiation of osteoblasts. Of the eight Ets family transcription factors examined by our laboratory, only Etsl and Ets2 were found to be expressed at significant levels in this osteogenic system. Etsl is expressed in proliferating preosteoblastic cells, whereas Ets2, silent during this phase, is expressed by differentiating and mature osteoblasts. In addition, the expression of Etsl can be induced in MC3T3-E1 and fetal rat calvaria cells by retinoic acid (RA) which is known to exert profound effects on skeletal growth and development and bone turnover and induce specific cellular responses in bone cells. Thus, the multiple functions of RA in bone cells are likely to be mediated in part by Etsl. We show that the expression of Ets2 precedes and then parallels osteopontin expression and that the OPN promoter contains Ets binding sites and is a transcriptional target of Ets2. In order to identify other potential Ets target genes, we analyzed promoter regions of genes revealed by serial analysis of gene expression as present in the differentiation stage. The functional analysis of these genes has the potential to provide much needed information as to their function in osteogenesis and mineralization of the extracellular matrix and in bone-related diseases.

Animals↗
PubMed2000

The Ets1 proto-oncogene is upregulated by retinoic acid: characterization of a functional retinoic acid response element in the Ets1 promoter.

The v-ets oncoprotein and its progenitor Ets1 belong to a family of transcription factors that are related by an 85 amino acid conserved DNA binding domain, the ets domain. Ets1 plays important role(s) in control of cell proliferation, differentiation and apoptosis. Abnormal expression of Ets1 could lead to disruption of these processes and contribute to development of malignancy. Retinoic acid (RA) inhibits proliferation, induces differentiation and regulates apoptosis in many different cell types. Here, we demonstrate that RA treatment increases the expression of Ets1 mRNA, but not that of Ets2, Elk1 or Fli1 in MC3T3-E1 cells. Ets1 induction is detectable after 4 h, can be maintained for at least 14 days, and is inhibited by Actinomycin D, which suggests that RA regulation of Ets1 occurs at the transcriptional level. The promoter region of Ets1 contains four retinoic acid response element (RARE) half sites located at -94, -152, -1765 and -2252 from the translation start site. We show that RARbeta is expressed by MC3T3-E1 cells in the presence of RA and demonstrate that it binds to the -94 RARE half site. Furthermore, RA induces transcription of Ets1 promoter-reporter constructs containing this RARE half site.

Cells, Cultured↗
PubMed2000

Oral ketamine in hepatocellular carcinoma.

Ketamine, an NMDA antagonist, has been used in pain treatment for a number of years. Recent reports have suggested its utility in a variety of pain states including post-herpetic neuralgia [1], cancer [2], and postoperative pain [5]. While a variety of neuropsychologic side effects are observed with parenteral ketamine, in oral use these side effects have been less pronounced [2,3]. We report a patient with severe hepatic disease who developed hallucinations following a 75-mg oral dose of ketamine for treatment of severe cancer pain unresponsive to morphine.

Journal Article↗
PubMed2000

Ah receptor-based chemical screening bioassays: application and limitations for the detection of Ah receptor agonists.

The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biologic and toxicologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. Here we utilized two AhR-dependent bioassay systems as screening tools to identify novel AhR agonists and to detect the presence of AhR agonists in sample extracts. These assays measure the ability of a chemical to activate AhR DNA binding in vitro (GRAB bioassay) or AhR-dependent (luciferase) gene expression in cultured cells (CALUX bioassay). Known AhR agonists (halogenated and nonhalogenated aromatic hydrocarbons) were positive in both assays, whereas the AhR antagonist alpha-naphthoflavone exhibited agonist activity only in the GRAB assay. In vitro GRAB analysis has identified several imidazoline receptor ligands and beta-carbolines as AhR agonists and also revealed the presence of AhR agonist activity in crude DMSO extracts of commercial newspapers. In contrast to their positive activity in the GRAB assay, the majority of these chemicals/extracts were only weakly active or inactive in the cell-based CALUX assay. Our results not only reveal that the ability of a chemical to activate the AhR in vitro does not necessarily correlate with its ability to induce gene expression in intact cells, but the high level of false positives obtained with the GRAB assay clearly demonstrates its inability to accurately identify AhR agonists or agonist activity. Screening of unknown chemicals, chemical classes, and samples for AhR agonist activity will require the use of intact cell bioassays.

Animals↗
PubMed1999

Low-pressure shunt 'malfunction' following lumbar puncture in children with shunted obstructive hydrocephalus.

Most shunt malfunctions present with signs and symptoms of high intracranial pressure, and computed tomography scans demonstrate ventricular enlargement. However, several authors have described a rare 'low-pressure' hydrocephalic state in which ventricular enlargement can occur in the face of low, or even negative, intracranial pressures. We report 2 children with obstructive hydrocephalus in whom this 'low-pressure state' followed a lumbar puncture; in both children, the shunts were functioning properly despite increased ventricular size on computed tomography scans, and all symptoms resolved (and the ventricles returned to baseline) following a period of enforced recumbency without shunt revision. We hypothesize that subarachnoid cerebrospinal fluid leakage through the puncture site in the lumbar theca decreases the intracranial pressures globally to a point below the opening pressures of the shunt valves. The ventricular cerebrospinal fluid, unable to be drained through either the subarachnoid space or the shunt, accumulates within the ventricular system under low pressure. One consistent feature in our 2 patients has been the postural nature of the headaches. We recommend enforced recumbency and, if necessary, a blood patch to seal the lumbar leakage. Shunt revision or prolonged external ventricular drainage appears to be unnecessary in these patients. Finally, neurosurgeons should be aware of this potential complication.

Cerebral Ventricles↗
PubMed1999

Immediate posttraumatic seizures: is routine hospitalization necessary?

OBJECTIVE: A recent Internet survey of pediatric neurosurgeons showed that 86% routinely admitted children with immediate posttraumatic seizures (PTS) for a brief period of observation. We wished to determine whether certain children meeting predefined criteria could instead be safely discharged from the emergency room. METHODS: We reviewed the records of children admitted during the past 5 years with a diagnosis of seizure and head injury. Children with a minor head injury, a PTS occurring within 24 h of injury and no intracranial abnormalities on admission CT scan were included. Children with previous neurological conditions, a history of prior seizures (other than PTS or febrile seizures), a prior history of anticonvulsant use, or intracranial abnormalities on the admission CT scan were excluded. Records were abstracted for child's age, gender, length of admission, previous history of PTS or febrile seizures, mechanism of injury, location of impact, time between impact and PTS, the number, length and type of PTS, Glasgow Coma Score (GCS) on admission, subsequent complications and hospital costs. RESULTS: Seventy-one children met the inclusion criteria. Eleven children presented to the emergency room with prolonged seizures, transient apnea or persistently low GCS and required admission to the intensive care unit (ICU). Among the 60 remaining children with simple PTS, none had further seizures during the follow-up period, and none had significant complications. The average cost of hospitalization was known for 58 children; after excluding the costs for 5 patients who were admitted to the ICU, the average hospital cost amounted to USD 1,615 per patient. CONCLUSIONS: Our data suggest that children with isolated minor head injuries and simple PTS who recover fully in the emergency room, whose CT scans show no intracranial abnormalities and who have no prior history of neurological disease, epilepsy or anticonvulsant use are at low risk for recurrent seizures or neurological complications, and could potentially be sent home to a reliable caretaker and a stable home situation. However, because of the limited sample size in this study, the statistical risk of a bad outcome may be as high as 9%; we therefore suggest that much larger studies are potentially needed before this becomes a standard policy.

Accidental Falls↗
PubMed1999

Tandem spinal cord injuries without radiographic abnormalities in a young child.

Anatomic features unique to the pediatric spine render this population susceptible to spinal cord injuries without radiographic abnormalities (SCIWORA). To date, published descriptions of SCIWORA have been limited to a single region of the spinal column. We describe a case of a 3-year-old boy in whom, after a motor vehicle accident, tandem SCIWORA lesions involving the lower cervical spinal cord and thoracolumbar junction resulted in severe quadraparesis. The child was initially treated with 24 h of methylprednisolone followed by 3 months of external orthoses of both the cervical and thoracic spine. We include in this article a brief review of the literature and treatment guidelines for SCIWORA and postulate the mechanism of these tandem spinal cord injuries.

Age Factors↗
PubMed1999

The results of a practice survey on the management of patients with shunted hydrocephalus.

The care of patients with shunted hydrocephalus is one of the most common clinical problems facing a pediatric neurosurgeon. Despite the prevalence of this clinical entity, it is our impression that the management strategies for these patients vary significantly amongst pediatric neurosurgeons. In an effort to better understand how varied these practices are, we surveyed 261 neurosurgeons with an expressed interest in pediatric neurosurgery, of whom 149 (57%) responded. The survey contained questions pertaining to preoperative and intraoperative management, choice of shunt valve, treatment philosophies with respect to shunt revision, evaluation process for potential shunt malfunction, treatment strategies for shunt infections and routine follow-up care. The answers to the questions confirmed our expectations that there are a variety of ways to manage these patients.

Anti-Bacterial Agents↗
PubMed1998

Pediatric neurosurgical disease.

The most common, primary referrals to a pediatric neurosurgeon's office are the evaluation and management of the child with a large head (to rule out hydrocephalus and other space occupying lesions) a mishappen head (to rule out various forms of craniosynostosis), or some form of congenital spinal abnormality (spinal dysraphism). The authors discuss the pathogenesis and clinical features of these disorders, provide a framework for diagnostic evaluation and referral, and discuss the various treatment options available for each.

Child, Preschool↗
PubMed1998

Serial radiography in the infant shaken impact syndrome.

Certain CT and/or MRI abnormalities have been used medicolegally to time intracranial injuries from the infant shaken impact syndrome (ISIS). For example, parenchymal hypodensities on CT scans are said to arise only after 6-48 h have elapsed postinjury, and the presence of chronic or mixed subdural hematomas suggests injury that occured 1-4 weeks prior. However, these statements are based largely upon inference from data obtained in other conditions such as ischemic anoxic injury and chronic subdural hemorrhage in adults. Direct evidence about the evolution of intracranial injuries in infants with ISIS is sparse, and the radiographic changes following ISIS have never been systematically studied on serial imaging studies. One hundred-seventeen serial CT and MRI scans obtained from 33 infants with ISIS were reviewed retrospectively. The exact scan dates and times were obtained directly from the scans. Acute subdural hemorrhage was the most common intracranial abnormality and was present in 27 (81%) of the 33 infants. Other intracranial abnormalities included chronic subdural collections, subarachnoid hemorrhage, epidural hematomas, parenchymal hypodensities, edema and contusions, and atrophy and encephalomalacia. In 15 of the 33 infants, the injury could be timed with reasonable certainty, and the evolution of the radiographic changes followed over time. Six of the 15 infants had evidence of prior cranial trauma such as chronic subdural collections (5 infants) or mild atrophy (1 infant). Of the remaining 9 infants, parenchymal abnormalities such as hypodensities, edema and contusion appeared in virtually all of the initial scans performed approximately 3 h following the report of injury. One 'chronic' subdural collection was absent on the first scan performed 2.75 h postinjury, but appeared on a second scan performed 17 h later, suggesting that some 'chronic' subdural fluid collections may arise much sooner than previously thought. These findings challenge some of the current dogma about the timing of radiographic changes following abuse and are important in timing the alleged abuse for legal purposes.

Battered Child Syndrome↗
PubMed1998

Midcervical postinfectious ligamentous instability: a variant of Grisel's syndrome.

OBJECTIVE AND IMPORTANCE: We report our recent experience with two cases of C3-C4 ligamentous instability that developed after the onset of an upper airway infection. To our knowledge, this is the first report in the literature of a variant of Grisel's syndrome occurring at the midcervical levels. The diagnosis and management of this entity are presented. CLINICAL PRESENTATION: Two infants with respiratory distress were evaluated at the Children's Hospital of Buffalo. During evaluation, cervical spine x-rays showed midcervical translational instability. Neither patient had a neurological deficit nor a history of trauma or bone disease. INTERVENTION: One of the patients was immmobilized with an external orthosis. CONCLUSION: Each patient remained neurologically intact, and the cervical spine returned to normal alignment after several months. We discuss a possible mechanism for this unusual association and recommend external immobilization.

Atlanto-Axial Joint↗
PubMed1998

The embryogenesis of congenital vertebral dislocation: early embryonic buckling?

Congenital vertebral dislocation (CVD) is a rare congenital spinal malformation characterized by a translatory or rotatory vertebral displacement, or both, at a single level, that results in an abrupt angulation of the neural canal. The more caudal vertebra is dysplastic and appears at first glance to be posteriorly dislocated into the vertebral canal as a posterior hemivertebra, but is actually well aligned with the more caudal vertebral column. Unfortunately, the present classification of complex congenital vertebral anomalies is confusing, and CVD has been grouped together with other congenital vertebral malformations under the terms 'segmental spinal dysgenesis', 'medial spinal aplasia', and others. Moreover, a putative embryonic mechanism has never been proposed for CVD. Based upon our experience with 6 children and a critical review of the literature, we identify CVD as a distinct entity having characteristic anatomical features. We propose a novel putative embryonic mechanism - early embryonic 'buckling' - which likely occurs by the 6th embryonic week, prior to the period of axonal outgrowth and the beginning of vertebral chondrification.

Female↗
PubMed1996

Cell cycle kinetics and commitment in newborn, adult, and tumoral astrocytes.

In terms of cell cycle phases, mammalian astrocytes maintain the capacity to leave G0/G1 and enter S phase in response to brain injury or due to neoplastic transformation. This report compares proliferative behavior in vitro, particularly departure from G0, in three types of rat astroglial cells-newborn astrocytes, astrocytes from gelatin implants into the traumatized striata of adults, and astrocytoma cells (C6 glioma). Newborn and adult astrocytes demonstrated nearly identical proliferation kinetics as determined by peaks in cell number and rates of DNA synthesis. C6 glioma (C6G) proliferated more rapidly. Exit from G0 was examined by shift-down of serum from 10 to 0.1% for 48 h, followed by return to 10% at time 0. Synchronization of newborn and adult astrocytes in this way resulted in a 12 h lag phase (G0/G1) followed by a 6-10-fold surge in DNA synthesis and a corresponding increase in S-phase nuclei from < 15% to > 70%. Timing of S-phase commitment was established in late G1 by resistance to the inhibitors cycloheximide and mevinolin. Decay of commitment was assessed by addition of hydroxyurea (HU) at 10 h to cause accumulation at the G1/S boundary. Removal of HU after an additional 14, 16, and 20 h resulted respectively in these percentages of maximal S-phase DNA synthesis in newborn and adult astrocytes: 75 +/- 9, 60 +/- 8, 23 +/- 3, and 87 +/- 20, 62 +/- 7, 34 +/- 5. In contrast, synchronization of C6G resulted in a 6 h lag before a surge in DNA synthesis and an increase in S-phase nuclei from < 20% to 100%. Cell cycle commitment occurred earlier with C6G, and decay of commitment was not observed, even after 20 h of HU treatment. Thus, these in vitro techniques for cell cycle analysis are applicable to astrocytes obtained from developing and adult brain, and to at least some astroglioma cells. Furthermore, this comparative study showed that important cell cycle parameters differ markedly in the non-tumoral astrocytes and glioma cells. These differences could lead to strategies for selective targeting of the proliferation of neoplastic astroglia.

Animals↗
PubMed1996

Engineered disulfide bonds in recombinant human interferon-gamma: the impact of the N-terminal helix A and the AB-loop on protein stability.

Insertion sites for cysteines with optimal stereochemistry for the formation of unstrained disulfide bridges were identified in recombinant human interferon-gamma (rhu-IFN-gamma) by computer modelling. We have engineered two different disulfide cross-linked mutants, containing a pair of symmetry-related disulfide bonds, which stabilize the N-termini of both monomers of the homodimeric protein. Mutations E7C and S69C allow the formation of an intramonomer disulfide bond between helices A and D. In contrast, the A17C and H111C mutations lead to a covalent cross-link between both monomers. The AB-loop is linked to helix F. The fluorescence properties of native and disulfide cross-linked proteins were studied as a function of guanidine hydrochloride concentration. Melting temperatures (Tm) were calculated from the decrease in CD ellipticity at 220 nm. The induction of the antiviral effect was measured using A549 fibroblast cells infected with encephalomyocarditis virus. The ability to induce the expression of the HLA-DR antigen in Colo 205 cells was determined by fluorescence-activated cell scanning analysis. The stability of both mutants was strongly enhanced against temperature- and cosolvent-induced unfolding. The delta Tm of mutant IFN-gamma E7C/S69C was 15 degrees C. All measured biological activities of this mutant were equal to wild type. In the case of the other mutant IFN-gamma A17C/H111C, the delta Tm value was 25 degrees C. This mutation abolishes nearly the entire biological activity (< 1%) with no detectable changes of secondary structure in the CD spectrum. Our results illustrate the importance of the N-terminal helix A and the AB-loop for the unfolding pathway and thermodynamic stability of rhu-IFN-gamma.

Circular Dichroism↗