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PubMed1980

Polarizing microscopy and microradiography of sound enamel.

Plano-parallel longitudinal sections from 19 sound human premolars were imbibed in water and in air. The total birefringence of the occlusal, the midcoronal and the cervical region of the buccal sound enamel cap was then determined. The volume percentage mineral was measured in the same areas using semi-quantitative microradiography. The results show that when the mean values of both water and air imbibed occlusal and midcoronal enamel are considered, there is a positive correlation between the observed total birefringence and the mineral content. The cervical, fissure and cuspal regions showed a poor correlation between mineral content and total birefringence. In longitudinal sections, the influence of the structural organization and the organic matrix is not marked in the occlusal and midcoronal regions although the cervical, fissure and cuspal regions are probably influenced to the greatest extent by these factors.

Air↗
PubMed2002

FGF10 maintains stem cell population during mouse incisor development.

Mouse incisors have a cervical loop that gives rise to dental epithelium in the apical region of the tooth germ, in contrast to molars. In a study of formation of the stem-cell compartment, we focused on expression patterns of fibroblast growth factor (Fgf) 10 and Fgf3 in developing mice incisors. At E14, Fgf10 and Fgf3 were coexpressed in the dental papilla. After E16 mesenchymal cells underlying cervical loop expressed Fgf10 but not Fgf3. To illustrate the role of FGF10, we analyzed incisor development of Fgf10-deficient mice. The germs of FGF10-null mice proceeded to cap stage normally. However, at a later stage, the cervical loop was not formed. Functional disorder of FGF10 by a neutralizing anti-FGF10 antibody induced apoptosis in the cervical loop of incisor explants. Recombinant FGF10 rescued the cervical loop from apoptosis. These results show that FGF10 maintains the stem-cell compartment in the developing incisor tooth germ.

Animals↗
PubMed2003

Corticospinal neurons up-regulate a range of growth-associated genes following intracortical, but not spinal, axotomy.

The failure of some CNS neurons to up-regulate growth-associated genes following axotomy may contribute to their failure to regenerate axons. We have studied gene expression in rat corticospinal neurons following either proximal (intracortical) or distal (spinal) axotomy. Corticospinal neurons were retrogradely labelled with cholera toxin subunit B prior to intracortical lesions or concomitantly with spinal lesions. Alternate sections of forebrain were immunoreacted for cholera toxin subunit B or processed for mRNA in situ hybridization for ATF3, c-jun, GAP-43, CAP-23, SCG10, L1, CHL1 or krox-24, each of which has been associated with axotomy or axon regeneration in other neurons. Seven days after intracortical axotomy, ATF3, c-jun, GAP-43, SCG10, L1 and CHL1, but not CAP-23 or krox-24, were up-regulated by layer V pyramidal neurons, including identified corticospinal neurons. The maximum distance between the lesion and the neuronal cell bodies that up-regulated genes varied between 300 and 500 microm. However, distal axotomy failed to elicit changes in gene expression in corticospinal neurons. No change in expression of any molecule was seen in the neocortex 1 or 7 days after corticospinal axotomy in the cervical spinal cord. The expression of GAP-43, CAP-23, L1, CHL1 and SCG10 was confirmed to be unaltered after this type of injury in identified retrogradely labelled corticospinal neurons. Thus, while corticospinal neuronal cell bodies fail to respond to spinal axotomy, these cells behave like regeneration-competent neurons, up-regulating a wide range of growth-associated molecules if axotomized within the cerebral cortex.

Animals↗
PubMed1992

Presynaptic histamine H1 and H3 receptors modulate sympathetic ganglionic synaptic transmission in the guinea-pig.

1. To study the effects of histamine on the efficacy of sympathetic ganglionic synaptic transmission, extracellular recordings of the postganglionic compound action potential (CAP) and intracellular recordings of excitatory postsynaptic potentials (EPSPs) elicited by preganglionic electrical stimulation were obtained from isolated guinea-pig superior cervical ganglia (SCG). 2. In different preparations, superfusion with histamine (0.1-100 microM) either potentiated or depressed the postganglionic CAP elicited by electrical stimulation of the cervical sympathetic trunk (0.2-3.0 Hz). The direction of response produced by histamine did not depend on stimulation frequency or histamine concentration; potentiation and depression both showed concentration dependence over the range of histamine concentrations tested. 3. Experiments employing a variety of histamine receptor agonists or antagonists revealed that histamine-induced potentiation of the postganglionic CAP could be attributed to histamine H1 receptor activation, and depression to H3 receptor activation. 4. Histamine similarly potentiated or depressed the intracellularly recorded EPSP. However, these opposite effects occurred at different synapses. In agreement with the studies on the postganglionic CAP, histamine H1 antagonists prevented histamine-induced potentiation of the EPSP and H3 receptor antagonists prevented histamine-induced depression. 5. Direct quantal analyses of histamine-induced synaptic potentiation and depression were implemented to determine the pre- and postsynaptic components of these effects. Quantal size was estimated by measuring the amplitude of spontaneous miniature EPSP amplitudes. Histamine-induced potentiation and depression of the evoked EPSP were found to be accompanied by increased or decreased quantal content respectively, and unchanged quantal size, providing evidence that presynaptic mechanisms were involved in mediating both effects. 6. Some guinea-pigs were actively sensitized to ovalbumin. Subsequent exposure of the isolated SCG from these animals to the sensitizing antigen produced changes in the EPSP amplitude that correlated significantly to the response produced by exogenously applied histamine at the same synapse. 7. The correspondence between the effects of specific antigen challenge and exogenous histamine on evoked EPSPs at a synapse provides evidence that endogenous histamine released during an immunological response to antigen challenge can activate histamine H1 and H3 receptors to modulate synaptic efficacy in sympathetic ganglia.

Action Potentials↗
PubMed2006

Cellulose acetate 1,2-benzenedicarboxylate inhibits infection by cell-free and cell-associated primary HIV-1 isolates.

Cellulose acetate 1,2-benzenedicarboxylate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was previously shown to have potent inhibitory activity against infection by human immunodeficiency virus type 1 (HIV-1) T cell line-adapted (TCLA) strains. In the present study, we determined the inhibitory activity of CAP against infection by cell-free and cell-associated primary HIV-1 isolates with distinct genotypes and biotypes in cervical explants, peripheral blood mononuclear cells (PBMCs), monocytederived macrophages (MDMs), and CEMx174 5.25M7 cells. CAP blocked infection by cell-free and cell-associated HIV-1 in cervical explants. It inhibited infection by cell-free primary HIV-1 isolates (clades A to G and group O) in PBMCs, MDMs, and CEMx174 5.25M7 cells and blocked transmissions of the cell-associated primary HIV-1 isolates from dendritic cells (DCs) to PBMCs, from MDMs to PBMCs, and from PBMCs to CEMx174 5.25M7 cells. The inhibitory activity of CAP on infection by the cell-free and cell-associated primary HIV-1 isolates is independent of viral subtypes and coreceptor usage. These data suggest that CAP is a good microbicide candidate that can be further developed for preventing sexual transmission of HIV-1.

Anti-HIV Agents↗
PubMed2006

Modern human molar enamel thickness and enamel-dentine junction shape.

This study examines cross-sections of molar crowns in a diverse modern human sample to quantify variation in enamel thickness and enamel-dentine junction (EDJ) shape. Histological sections were generated from molars sectioned buccolingually across mesial cusps. Enamel cap area, dentine area, EDJ length, and bi-cervical diameter were measured on micrographs using a digitizing tablet. Nine landmarks along the EDJ were defined, and X and Y coordinates were digitized in order to quantify EDJ shape. Upper molars show greater values for the components of enamel thickness, leading to significantly greater average enamel thickness than in lower molars. Average enamel thickness increased significantly from M1 to M3 in both molar rows, due to significantly increasing enamel cap area in upper molars, and decreasing dentine area in lower molars. Differences in EDJ shape were found among maxillary molars in combined and individual populations. Sex differences were also found; males showed significantly greater dentine area, EDJ length, and bi-cervical diameters in certain tooth types, which resulted in females having significantly thicker average enamel. Differences in enamel thickness and EDJ shape within molars were also found among populations, although few consistent trends were evident. This study demonstrates that enamel thickness and EDJ shape vary among molars, between sexes, and among populations; these factors must be considered in the categorization and comparison of ape and human molars, particularly when isolated teeth or fossil taxa are included. Human relative enamel thickness encompasses most values reported for fossil apes and humans, suggesting limited taxonomic value when considered alone.

Animals↗
PubMed1993

Use-dependent fade and two-rate recovery of a naloxone-sensitive inhibition in the cat superior cervical ganglion.

In anaesthetized cats, a short train to the cervical sympathetic trunk (CST), of frequency between 0.5 and 5.0 Hz, inhibited the postganglionic compound action potential (CAP) evoked by a test shock to the CST. When the CST was split into two bundles, the inhibition was obtained both homosynaptically and heterosynaptically. The inhibition was antagonized by naloxone and enhanced by peptidase inhibitors. Leu-enkephalin (ENK), injected into the arterial supply of the superior cervical ganglion (SCG) depressed the CAP. The ENK-evoked inhibition was antagonized by naloxone, enhanced by peptidase inhibitors and was occluded by the train-evoked inhibition. After prolonged stimulation of the CST (5-20 min at 5 Hz), the inhibition produced by a short train was depressed (faded). The fade was greater the longer the stimulation. After 20 min of stimulation the inhibition was absent. At this time the depressant effect of ENK was unchanged. When only one bundle of the split CST was stimulated at 5 Hz for 20 min, only the inhibition produced by that bundle faded, although both bundles converged onto a common set of ganglion cells. Thus, the fade is not due to receptor desensitization but more likely to failure to release the inhibitory mediator by the overstimulated axons. When, after 20 min of 5 Hz stimulation, no further stimuli were applied, the inhibition recovered in 60 min (fast recovery). However, recovery was slower when stimulation lasted longer than 20 min. Recovery took three days when stimulation lasted 80 min (slow recovery). The inhibition was markedly depressed after application of colchicine to the CST three days earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Naloxone-sensitive inhibition of nicotinic transmission in the superior cervical ganglion of the cat.

In anesthetized, artificially ventilated cats, pretreated with the muscarinic antagonist scopolamine, the effect of naloxone on the efficacy of nicotinic transmission in the superior cervical ganglion was used as a test of endogenous opioid release by the preganglionic axons. The cervical sympathetic trunk (CST) was split into two bundles. The compound action potential (CAP), evoked by supramaximal low-frequency stimulation (0.25 Hz) of one CST bundle, was recorded from a postganglionic nerve of the superior cervical ganglion. Partial block with hexamethonium was used to reduce the 'safety factor' of nicotinic transmission. A conditioning train (5 Hz, 40 s, supramaximal) to the other CST bundle (heterosynaptic conditioning) inhibited the CAP. At the peak of the inhibition the CAP was attenuated by 51 +/- 4%. Recovery was 90% complete in 201 +/- 28 s. The inhibition was antagonized in a dose-dependent manner by i.v. naloxone with an apparent IC50 of 60 +/- 12 micrograms/kg. The maximum effect obtained with naloxone was an 80% decrease in the magnitude of the inhibition. Magnitude and duration of the heterosynaptic inhibition were related to frequency, duration and intensity of the conditioning train. Naloxone-sensitive inhibition was observed with frequencies of the conditioning train as low as 0.5 Hz. A train (5 Hz, 40 s) to the postganglionic nerves produced a naloxone-insensitive depression of the orthodromic test CAP which was of smaller amplitude and duration than when the conditioning train was applied to the preganglionic axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

[Pathophysiological studies in moyamoya disease by rCBF and cortical artery pressure measurements in comparison to those in ICA or MCA occlusion].

The authors measured preoperative rCBF and intraoperative cortical artery pressure (CAP) during STA-MCA anastomosis to investigate cerebral hemodynamics in moyamoya disease. Six of 13 patients including 3 children showed ischemic attack and the remaining presented hemorrhagic attack. rCBF was measured by single photon ECT with Xe-133 inhalation technique. CAP's and rCBF's in moyamoya disease were compared to those in the 22 internal carotid artery (ICA) and 8 middle cerebral artery (MCA) occlusion. Systemic arterial blood pressure (SABP) was obtained at the radial artery. Mean rCBF in the MCA territory in moyamoya disease, ICA occlusion, and MCA occlusion were 39, 37, and 33 ml/100 g/min respectively. Mean SABP and CAP in moyamoya disease were 103 and 28 mmHg, respectively. In ICA occlusion, mean SABP and CAP were 98 and 45 mmHg, respectively. In MCA occlusion, mean SABP and CAP were 89 and 36 mmHg, respectively. To clarify the hemodynamics, vascular resistance was obtained from the following equations: The proximal vascular resistance (Rp), which was produced from the cervical ICA to cortical artery, was obtained by (mean SABP - mean CAP)/(rCBF). And distal vascular resistance (Rd) which was produced from the cortical artery to jugular vein, was obtained by (mean CAP)/(rCBF). Mean Rp in moyamoya disease ICA occlusion and MCA occlusion were 2.01, 1.21 and 1.70, respectively. Rd in moyamoya disease, ICA occlusion and MCA occlusion were 0.79, 1.37 and 1.22, respectively. There were significant differences in Rp and Rd between moyamoya disease and ICA or MCA occlusion. In ischemic group in moyamoya disease, rCBF, SABP, CAP, Rp and Rd were 41 ml/100 g/min, 111 mmHg, 28 mmHg, 1.92 and 0.70, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗
PubMed2002

FGF10 maintains stem cell compartment in developing mouse incisors.

Mouse incisors are regenerative tissues that grow continuously throughout life. The renewal of dental epithelium-producing enamel matrix and/or induction of dentin formation by mesenchymal cells is performed by stem cells that reside in cervical loop of the incisor apex. However, little is known about the mechanisms of stem cell compartment formation. Recently, a mouse incisor was used as a model to show that fibroblast growth factor (FGF) 10 regulates mitogenesis and fate decision of adult stem cells. To further illustrate the role of FGF10 in the formation of the stem cell compartment during tooth organogenesis, we have analyzed incisor development in Fgf10-deficient mice and have examined the effects of neutralizing anti-FGF10 antibody on the developing incisors in organ cultures. The incisor germs of FGF10-null mice proceeded to cap stage normally. However, at a later stage, the cervical loop was not formed. We found that the absence of the cervical loop was due to a divergence in Fgf10 and Fgf3 expression patterns at E16. Furthermore, we estimated the growth of dental epithelium from incisor explants of FGF10-null mice by organ culture. The dental epithelium of FGF10-null mice showed limited growth, although the epithelium of wild-type mice appeared to grow normally. In other experiments, a functional disorder of FGF10, caused by a neutralizing anti-FGF10 antibody, induced apoptosis in the cervical loop of developing mouse incisor cultures. However, recombinant human FGF10 protein rescued the cervical loop from apoptosis. Taken together, these results suggest that FGF10 is a survival factor that maintains the stem cell population in developing incisor germs.

Animals↗
PubMed1999

Adeno-associated virus and development of cervical neoplasia.

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.

Adolescent↗
PubMed1997

Mouse molar morphogenesis revisited by three-dimensional reconstruction. III. Spatial distribution of mitoses and apoptoses up to bell-staged first lower molar teeth.

Computer-assisted 3D reconstructions were used to follow the development of the embryonic mouse first lower molar (M1). At ED 12.5, the thickening of the oral epithelium, which was thought to correspond to the molar dental lamina, regressed in its anterior part as a result of apoptosis. Only the posterior part later gave rise to molars. The transition to the cap stage entailed medial and lateral extensions of the dental epithelium. The growth and histo-morphogenesis of the enamel organ as well as cervical loop formation proceeded more rapidly in the anterior part of the M1 during the cap and early bell stages producing significant morphological differences along the antero-posterior axis. Apoptosis was temporarily intensive in the anterior part of the bud- and cap-shaped epithelium and thus pointed domains which do not participate in the formation of the final M1 enamel organ. In the well-formed cap, apoptoses displayed maximum concentration in the enamel knot (EK). No increase in the number of metaphases could be detected in the vicinity of the EK. Mitoses were distributed throughout the epithelial compartment until cap stage and then mainly concentrated in the inner dental epithelium at the early bell stage. At this later stage, either lateral views or thick virtual sections performed in the reconstruction demonstrated a clear cut distribution of mitoses and apoptoses in the enamel organ. At the early bell stage, mitoses in the mesenchyme demonstrated an increasing postero-anterior gradient.

Animals↗
PubMed2002

Vanilloid receptors presynaptically modulate cranial visceral afferent synaptic transmission in nucleus tractus solitarius.

Although the central terminals of cranial visceral afferents express vanilloid receptor 1 (VR1), little is known about their functional properties at this first synapse within the nucleus tractus solitarius (NTS). Here, we examined whether VR1 modulates afferent synaptic transmission. In horizontal brainstem slices, solitary tract (ST) activation evoked EPSCs. Monosynaptic EPSCs had low synaptic jitter (SD of latency to successive shocks) averaging 84.03 +/- 3.74 microsec (n = 72) and were completely blocked by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX). Sustained exposure to the VR1 agonist capsaicin (CAP; 100 nm) blocked ST EPSCs (CAP-sensitive) in some neurons but not others (CAP-resistant). CAP-sensitive EPSCs had longer latencies than CAP-resistant EPSCs (4.65 +/- 0.27 msec, n = 48 vs 3.53 +/- 0.28 msec, n = 24, respectively; p = 0.011), but they had similar jitter. CAP evoked two transient responses in CAP-sensitive neurons: a rapidly developing inward current (I(cap)) (108.1 +/- 22.9 pA; n = 21) and an increase in spontaneous synaptic activity. After 3-5 min in CAP, I(cap) subsided and ST EPSCs disappeared. NBQX completely blocked I(cap). The VR1 antagonist capsazepine (10-20 microm) attenuated CAP responses. Anatomically, second-order NTS neurons were identified by 4-(4-dihexadecylamino)styryl)-N-methylpyridinium iodide transported from the cervical aortic depressor nerve (ADN) to stain central terminals. Neurons with fluorescent ADN contacts had CAP-sensitive EPSCs (n = 5) with latencies and jitter similar to those of unlabeled monosynaptic neurons. Thus, consistent with presynaptic VR1 localization, CAP selectively activates a subset of ST axons to release glutamate that acts on non-NMDA receptors. Because the CAP sensitivity of cranial afferents is exclusively associated with unmyelinated axons, VR1 identifies C-fiber afferent pathways within the brainstem.

Animals↗
PubMed2002

It is easier to confuse a jury than convince a judge: the crisis in medical malpractice.

STUDY DESIGN: A study of cervical spine malpractice cases was conducted. Identifying tort reform models may help to resolve a crisis in medical malpractice. OBJECTIVE: To identify tort reform models that may help to resolve a crisis in medical malpractice. SUMMARY OF BACKGROUND DATA: Medical malpractice faces a crisis. Insurance rates are exorbitant, yet many injured patients go uncompensated. Physicians practice defensive medicine for fear of suits, and society pays the price. METHODS: Using, 36 malpractice cases involving cervical spine surgery were identified: 20 from California ($250,000 cap on pain and suffering) and 16 from New York ("the sky's the limit"). Queries included who sued, who was sued, who won, who lost, and why? Six different tort reform models also were identified and explored. RESULTS: Common bases for suits included failure to diagnose and treatment (56%), lack of informed consent (64%), new neurologic deficits (64%), and pain and suffering (72%). All of the six plaintiff verdicts (average, $4.42 million) and four of the nine settlements (average, $1.6 million) involving surgery that resulted in new postoperative quadriplegia appeared to be appropriate. However, the author could discern "no fault" in cases five defendants had settled, and the surgeons did not deserve to lose. On the other hand, the author found "fault" in five defense verdicts rendered to three newly quadriplegic patients and two with new postoperative root injuries. These patients deserved monetary awards, but received no compensation whatsoever. There currently are two models that would work better than the system in place in most states. These include the American Medical Association National Specialty Societies Medical Liability Project with the Alternative Dispute Resolution Model (SSMLP), and the Selective No Fault Models. Among the advantages shared by one or more of these models is their ability to reimburse injured patients while eliminating physician liability, to use malpractice panels rather than trials, and to put a cap on damages. CONCLUSIONS: To solve the medical malpractice crisis, Congress, the individual states, or both should adopt tort reform. Two tort reform models compensating injured patients and eliminating physician liability appear to be not only effective but also fair to all concerned parties.

California↗
PubMed2000

Sensitivity of peripheral nerve fibres to sodium pentobarbital anaesthesia in rat.

The sensitivity of different classes of peripheral nerve fibres to anaesthesia with sodium pentobarbital in rat was tested. The basic approach was to examine changes in compound action potential (CAP) in a rat sural nerve induced by sodium pentobarbital. Rats were either sacrificed by cervical dislocation (control) or anaesthetized with sodium pentobarbital (100 mg/kg, i.p.), and a 30 mm long sural nerve segment excised and placed on electrodes in a thermostatically controlled recording chamber. CAPs were evoked by electrically stimulating the sural nerve segment with supra-threshold stimuli. CAP in control sural nerves consisted of the early component (A axons: 32.73 +/- 2.91 m/s) and the late component (C axons: 0.92 +/- 0.05 m/s) with peak voltage amplitudes 4.9 +/- 1.0 mV and 0.1 +/- 0.03 mV, respectively. Anaesthesia with sodium pentobarbital had no effect on CAP latency. However, the amplitude of CAP of both A and C axons was reduced by approximately 40% and 50%, respectively. The depressant effect of pentobarbital on CAPs was statistically significant for both groups of axons (p<0.01). Non-selective sensitivity of A and C axons to pentobarbital suggests even distribution of receptors for GABA in these two populations of axons in the rat peripheral nerve.

Action Potentials↗
PubMed2004

Splicing of a cap-proximal human Papillomavirus 16 E6E7 intron promotes E7 expression, but can be restrained by distance of the intron from its RNA 5' cap.

Human papillomavirus 16 (HPV16) E6E7 pre-mRNA is bicistronic and has an intron in the E6 coding region with one 5' splice site and two alternative 3' splice sites, which produce E6(*)I and E6(*)II, respectively. If this intron remains unspliced, the resulting E6E7 mRNA expresses oncogenic E6. We found for the first time that the E6E7 pre-mRNA was efficiently spliced in vitro only when capped and that cellular cap-binding factors were involved in the splicing. The cap-dependent splicing of the E6E7 pre-mRNA was extremely efficient in cervical cancer-derived cells, producing mostly E6(*)I, but inefficient in cells transfected with a common retrovirus expression vector, pLXSN16E6E7, due to the large size of this vector's exon 1. Further studies showed that efficient splicing of the E6E7 pre-mRNA depends on the distance of the cap-proximal intron from the RNA 5' cap, with an optimal distance of less than 307nt in order to facilitate better association of U1 small nuclear RNA with the intron 5' splice site. The same was true for splicing of human beta-globin RNA. Splicing of the E6E7 RNA provided more E7 RNA templates and promoted E7 translation, whereas a lack of RNA splicing produced a low level of E7 translation. Together, our data indicate that the distance between the RNA 5' cap and cap-proximal intron is rate limiting for RNA splicing. HPV16 E6E7 pre-mRNA takes advantage of its small cap-proximal exon to confer efficient splicing for better E7 expression.

3' Flanking Region↗
PubMed2005

eIF-4E expression is associated with histopathologic grades in cervical neoplasia.

Translation initiation factor eIF-4E (eukaryotic initiation factor 4E) is a 25 kd messenger RNA cap-binding phosphoprotein and is involved in the initiation of protein synthesis. The expression is known to be elevated in several carcinomas as compared with normal tissues and benign lesions. In the present study, we undertook to determine whether eIF-4E expression is associated with progression in cervical neoplasia. eIF-4E expression was evaluated by immunohistochemistry in 88 formalin-fixed, paraffin-embedded cervical tissues; 10 normal cervical specimens; 19 low-grade cervical intraepithelial neoplasias (CINs); 19 high-grade CINs; and 40 invasive squamous cell carcinomas (ISCCs). In addition, eIF-4E expression was evaluated at the RNA level in fresh frozen cervical carcinoma tissues by real-time quantitative reverse transcriptase polymerase chain reaction. Immunohistochemical staining showed that eIF-4E expression was undetectable in most normal cervical squamous epithelial tissues (90%), but variable staining was observed in the basal layer of all normal endocervical glands. eIF-4E expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with histopathologic grade in the order low-grade CIN < high-grade CIN < ISCC (P < .001) and, in particular, was strongly detected in all ISCC cases. Furthermore, real-time quantitative reverse transcriptase polymerase chain reaction revealed that eIF-4E expression in tumor was significantly enhanced versus normal cervical tissues (P = .037). These results suggest that eIF-4E may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells.

Biomarkers, Tumor↗
PubMed1998

Randomized comparison of Guglielmi detachable coils and cellulose acetate polymer for treatment of aneurysms in dogs.

BACKGROUND AND PURPOSE: Endovascular treatments for aneurysms are being used more frequently in patients in the absence of a large body of information on their histopathological effects. This study determined the efficacy and histopathological effects of treatment of experimental aneurysms with Guglielmi detachable coils (GDC) or cellulose acetate polymer (CAP). METHODS: Fourteen dogs had 13 terminal and 30 sidewall aneurysms created with venous pouches sutured to the cervical carotid arteries. Two weeks later, dogs had angiography followed by randomization to no treatment (n=2) or to aneurysm occlusion with GDC (n=4) or CAP (n=6). Two months later, angiography was repeated, animals were killed, and aneurysms were excised, fixed, photographed, and examined by light and electron microscopy. RESULTS: Two dogs were excluded because of common carotid artery occlusion at 2-week angiography. There were 11 terminal and 16 sidewall aneurysms available for treatment. The rate of spontaneous thrombosis of untreated aneurysms was 0% (0/5). Treatment with GDC showed complete terminal and sidewall aneurysm obliteration rates of 33% (1/3) and 80% (4/5), respectively. Greater than 90% occlusion occurred in the remaining cases. There were no parent or branch artery occlusions. Treatment with CAP showed complete terminal and sidewall aneurysm obliteration rates of 20% (1/5) and 0% (0/5), respectively, and incomplete sidewall aneurysm obliteration in 1 of 5 cases. Aneurysms reformed at 2 months in 2 of 5 terminal and 1 of 5 sidewall cases. There were parent or branch artery occlusions with CAP in 2 and 4 cases, respectively. The rate of aneurysm occlusion was significantly lower and the rate of arterial occlusion significantly higher with CAP than with GDC (P<.05). Histopathology showed complete endothelialization across the orifice of the aneurysm successfully treated with CAP, whereas aneurysms treated with GDC were significantly more likely to show fresh or organizing thrombus without complete endothelialization (P<.05). CONCLUSIONS: It is concluded that both treatments have limitations. Complete packing of aneurysms with GDC obliterates the aneurysm, but endothelialization does not always occur within 2 months. There are substantial problems with CAP. It is thrombogenic and carries a higher risk of causing arterial thrombosis. Even if an aneurysm is successfully obliterated initially with CAP, the CAP may disappear, leaving the aneurysm completely untreated.

Animals↗