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A 29-year-old man presented with a chief complaint of lateral blindness in the left eye at 4 months after an accidental fall. His best corrected visual acuity was 0.7 in the left eye and 1.0 in the right eye. Visual field test showed a complete bitemporal hemianopic defect without any neurologic symptoms. An orbital computed tomography scan with non-enhancement conducted at the time of the visit showed multiple frontal skull fractures and cerebromalacia a small fracture in the sphenoidal boneboth frontal lobes. No radiological abnormalities of the visual pathway were detected. Optical coherence showed reduced thickness in the retinal nerve fiber layer, primarily in the superior and inferior part of the left eye. To our knowledge, a complete bitemporal hemianopia without neurological deficits is extremely rare in traumatic chiasmal syndrome.

Aim: To evaluate the characteristics of pupillo-accommodative functions in patients with idiopathic tonic pupil according to the time of onset, gender, and age., Methods: Totally, 15 males and 19 females were divided into 2 groups depending on the time of disease onset: group I (onset <2 months, n=20) and group II (onset >2 months, n=14). A supersensivity test was conducted by applying diluted pilocarpine 0.125% to the eye and accommodative functions were evaluated using the near-point of accommodation (NPA) as the cutoff point, at which the patient experienced blurred vision. Pupil size and the ratio of decrease in the affected pupil after instillation of 0.125% pilocarpine were investigated., Results: There was no significant difference between the 2 groups regarding the various pupillary reflex results, including data on the affected pupil size before and after 0.125% pilocarpine, anisocoria, and ratio of pupil decrease. No significant difference in NPA was found between the 2 groups. However, female patients were noted to have greater anisocoria and a faster constriction ratio than those of the male patients (P=0.02 and P=0.04). On subgroup analysis, female patients from group II had larger affected-pupil sizes before 0.125% pilocarpine instillation and longer NPAs than those of the male patients., Conclusion: No relationship was found between time of onset and dysfunction of pupillo-accommodative functions. Pupillo-accommodative functions and age were not related, except for the NPA.

Purpose: The purpose of this study is to investigate optic nerve head using spectral domain optical coherence tomography (SD-OCT) in children with large cupping., Methods: 111 eyes (4-10 years) were divided into three groups according to the cup to disc ratio: group 1, ≤0.3; group 2, 0.4-0.6; and group 3, ≥0.7. The rim area, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume were investigated using SD-OCT (Cirrus HD-OCT, Carl Zeiss, Jena, Germany), and the axial length and anterior chamber depth (ACD) were measured by IOL master (IOL master 500, Carl Zeiss, Jena, Germany). Next, we compared ocular biometry and SD-OCT between the three groups., Results: The mean age of group 1 was 6.48 ± 1.42 years, 7.00 ± 1.75 years in group 2, and 6.63 ± 1.82 years in group 3 (p = 0.370). A significant difference was seen in the spherical equivalent between the groups (p = 0.001). Group 2 had the most myopic refractive errors. As the cup to disc ratio increases, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume increase significantly. When the results of ocular biometry and SD-OCT are adjusted for axial length, only disc area showed a significant correlation with cup to disc ratio (ACD: p = 0.473, rim area: p = 0.639, disc area: p = 0.005, and cup volume: p = 0.325)., Conclusion: Axial length is the key factor determining disc size, which in turn is important for determining cup to disc ratio. Normal children with large cupping should be examined for axial length, myopic refractive errors, and disc size.

Introduction: To report spectral domain optical coherence (OCT) tomography findings in a case of bilateral peripheral cone dystrophy., Case Report: A 21-year-old man complained of blurred visual fields on the lateral sides of both eyes. The patient's best-corrected visual acuity was 20/20 in both eyes. Fundus examination revealed mild temporal pallor, while fluorescein angiography did not show any abnormalities. Humphrey's visual field revealed a C-shaped scotoma. Photopic electroretinogram (ERG) and 30-Hz flicker revealed decreased cone function; however, scotopic ERG noted a normal response. Multifocal ERG revealed a relatively well-preserved macular area but with reduced amplitude in the peripheral areas of both eyes. On OCT, the photoreceptor inner and outer segment junction and retinal pigment epithelium (RPE) layers were well preserved in both eyes, except for a slight decrease in outer layer thickness. Moreover, on the macular thickness map obtained from Cirrus HD-OCT, a reduction in internal limiting membrane-RPE thickness that correlated well with visual field defects was revealed in both eyes. On the retinal nerve fiber layer (RNFL) thickness map obtained from Cirrus HD-OCT, the superior quadrant showed decreased RNFL thickness; however, thickness in the temporal quadrant corresponded with thickness in the macular area and was normal in both eyes., Discussion: The OCT of a patient with peripheral cone dystrophy revealed decreased thickness of the macula with well-preserved retinal structures, which may be one of the distinctive features of this condition.

Purpose: To define the long-term results of accommodation insufficiency and to investigate the correlation between accommodation insufficiency and other factors including near point of convergence (NPC), age, and refractive errors., Methods: From January 2008 to December 2009, 11 patients with acute near vision disturbance and remote near point of accommodation (NPA) were evaluated. Full ophthalmologic examinations, including best corrected visual acuity, manifest refraction and prism cover tests were performed. Accommodation ability was measured by NPA using the push-up method. We compared accommodation insufficiency and factors including age, refractive errors and NPC. We also investigated the recovery from loss of accommodation in patients., Results: Mean age of patients was 20 years (range, 9 to 34 years). Five of the 11 patients were female. Mean refractive error was -0.6 diopters (range, -3.5 to +0.25 diopters) and 8 of 11 patients (73%) had emmetropia (+0.50 to -0.50 diopters). No abnormalities were found in brain imaging tests. Refractive errors were not correlated with NPA or NPC (rho = 0.148, p = 0.511; rho = 0.319, p = 0.339; respectively). The correlation between age and NPA was not significant (rho = -395, p = 0.069). However, the correlation between age and NPC was negative (rho = -0.508, p = 0.016). Three of 11 patients were lost to follow-up, and 6 of 8 patients had permanent insufficiency of accommodation., Conclusions: Accommodation insufficiency is most common in emmetropia, however, refractive errors and age are not correlated with accommodation insufficiency. Dysfunction of accommodation can be permanent in the isolated accommodation insufficiency.

Purpose: To evaluate the correlation between hypertropia and excyclotorsion in acquired superior oblique palsy (SOP)., Methods: Thirty-one patients with acquired unilateral SOP were recruited for this study. The torsional angle of each patient was assessed via one objective method (fundus photography) and two subjective methods (double Maddox rod test and major amblyoscope). The patient population was divided into two groups (concordance group, n = 19 and discordance group, n = 12) according to the correspondence between the hypertropic eye (paralytic eye) and the more extorted eye (non-fixating eye), which was evaluated by fundus photography., Results: The mean value of objective torsion was 5.09° ± 3.84°. The subjective excyclotorsion degrees were 5.18° ± 4.11° and 3.65° ± 1.93° as measured by double Maddox rod test and major amblyoscope, respectively. Hypertropia and the excyclotorsional angle did not differ significantly between the groups (p = 0.257). Although no correlation was found in the discordance group, the concordance group showed a significant and positive correlation between hypertropia and excyclotorsion (p = 0.011)., Conclusions: Torsional deviation was not related to hypertropia. However, in the concordance patients in whom the hypertropic eye showed excyclotorsion, a significant positive correlation was found between hypertropia and excyclotorsion.

Purpose: To evaluate the psychosocial distress of part-time occlusion therapy in intermittent exotropia., Methods: A total of 25 children (15 males and 10 females, aged 3 to 7 years, mean age 4.7 years) with intermittent exotropia were enrolled. Behavioral and psychosocial problems were assessed by the Korean Child Behavior Checklist (K-CBCL), which consists of eight categories of withdrawal, somatic problems, depression/anxiety, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior, and the Amblyopia Treatment Index (ATI). The ATI was designed to evaluate the three factors of compliance, adverse effect, and social stigma. The Parenting Stress Index (PSI) is a parent self-report designed to identify potentially dysfunctional parent-child systems. The K-CBCL was obtained before and after occlusion therapy, and the ATI and PSI were taken from parents only after occlusion therapy. We evaluated the change on the K-CBCL and the correlation between the K-CBCL and ATI., Results: The attention problem assessed by the K-CBCL significantly decreased after occlusion therapy. On the ATI, the social stigma was relatively lower than compliance and adverse effect factors (Likert scale 2.64, 3.11, and 3.11, respectively). The somatic problem assessed by the K-CBCL and compliance on the ATI were significantly correlated (p = 0.014). There was no significant change in percentile scores of each subscale (parental dominant scale and child dominant scale) of the PSI. Total stress index before and after occlusion therapy was 97.16 ± 8.38 and 97.00 ± 8.16 respectively (p = 0.382)., Conclusions: Occlusion therapy may influence the psychosocial impact on intermittent exotropia patients. Part-time occlusion significantly decreased the attention problem in children with intermittent strabismus. Children with a high somatic problem score on the KCBCL showed poor compliance to the part-time occlusion.

Purpose: The effects of amiloride on cellular toxicity caused by tissue plasminogen activator (tPA) in mouse primary retinal cells were investigated., Methods: Primary retinal cell cultures were maintained using glial conditioned medium. Commercial tPA and L-arginine were added, and the level of cyclic guanosine monophosphate (cyclic-GMP) in the culture supernatant was assessed using an ELISA assay. We measured the cell viability of cultured retinal cells pretreated with three different concentrations of amiloride (1, 10, and 100 µm) in addition to commercial tPA or L-arginine treatment., Results: After exposing the cultured mouse retinal cells to tPA plus L-arginine or L-arginine alone, cyclic-GMP concentrations were 61.9 ± 5.1 pmole/mL and 63.1 ± 6.1 pmole/mL, respectively. However, the control group had a significantly lower concentration of cyclic-GMP (37.2 ± 3.4 pmole/mL, p < 0.01). The cyclic GMP-dissolved solution did not cause retinal cell death. In the control group and the group treated with 1 µm amiloride and tPA containing L-arginine, the cell viability was 43.7% and 44.5%, respectively. However, cell viability increased to 70.6% with 10 µm amiloride and 78.4% with 100 µm amiloride (p = 0.015)., Conclusions: L-arginine increases intracellular cyclic-GMP and may give rise to retinal cells through this mechanism. In addition, amiloride in concentrations greater than 10 µm protects against L-arginine-induced retinal cell death.

Background: The hang-back surgery is a useful technique in the field of strabismus surgery. The aim of this study is to determine the stabilizing effects of fibrin glue as an adjuvant to hang-back surgery., Materials and Methods: Four (4)-mm hang-back recessions of the superior rectus muscle was performed in 32 eyes of 16 rabbits. Only in the left eye of the 16 rabbits, fibrin glue was applied between the recessed muscle bed and the sclera at the end of hang-back surgery (fibrin glue group). After 6 weeks, we compared the stability of the recessed rectus muscle between the fibrin glue group and the control group by evaluating the displacement of the muscle., Results: The frequency of stable insertion of the recessed muscle at the intended site was greater in the fibrin glue group (9 eyes) compared to the control group (3 eyes) (p=0.028). In the control group, 5 eyes showed anterior displacement and 8 eyes showed posterior displacement and in the fibrin glue group, 1 eye showed anterior displacement, and 6 eyes showed posterior displacement. Anterior displacement was more common in the control group (6.3% Vs 31.3%). The control group and the fibrin glue group showed similar histological findings on microscopic examination., Conclusions: Fibrin glue is effective in stabilizing the new rectus muscle insertion and decreasing the displacement in the hang-back surgery.

Purpose: To determine methods tried in clinical trials to reduce the progression of myopia in children, and spectacle prescribing patterns of hospital ophthalmologists., Methods: A multi-sectioned survey composed of Likert items relating to the methods of reducing myopia progression (orthokeratology lenses [O-K lenses], undercorrected glasses, and topical atropine) and the patterns of prescribing spectacles for children (including two cases involving a 5-year-old girl and an 8-year-old boy) were distributed to members of the Korean Ophthalmological Society, and the collected data was statistically analyzed., Results: A total of 78 out of 130 ophthalmologists returned the survey. On a scale of 1 to 5, the mean rates of whether the ophthalmologists think O-K lenses arrest myopia progression, and whether they recommend their patients to wear O-K lenses if indicative, were 3.06 and 2.75, respectively. Moreover, the mean rates of whether they consider that wearing glasses which are undercorrected would slow down the progression of the myopia, or if they think topical atropine helps in arresting myopia progression in children, were 2.34 and 1.27, respectively. In response to the case studies, the majority of practitioners preferred to prescribe the full amount found in cycloplegic refraction to pediatric patients with myopia., Conclusions: Ophthalmologists in clinical practice encouraged children to wear O-K lenses more than undercorrected glasses as a way to retard myopia progression. However, the application of atropine is rarely tried in clinical trials. In managing pediatric patients with myopia (case specific), the majority of the practitioners chose to prescribe glasses with full cycloplegic correction.

An 8-year-old boy presented with amblyopia and magnetic resonance imaging examination revealed moderately dilated optic nerve sheath with fluid. The diagnosis of unilateral optic nerve sheath meningocele was made and this case was not associated with type I neurofibromatosis. The authors report an additional case of isolated unilateral optic nerve sheath meningocele., (Copyright 2011, SLACK Incorporated.)

Purpose: To evaluate the reproducibility of ImageJ software in analyzing the color of the optic disc., Methods: One hundred twelve normal participants (56 males and 56 females) were enrolled in this study. The image of the optic disc was taken using Kowa digital disc photo-graphy, and the gray scales of the nasal rim (NR), brightest cupping center (BCC) and largest inferior retinal vein (IRV) were calculated using histogram in ImageJ. Three different observers calculated the gray scales three separate times. Reproducibility was assessed using the interclass correlation coefficient (ICC)., Results: The mean age of the participants was 50.6 years old (range, 11 to 82 years). The mean gray scales of the nasal rim were 91.81, 94.91, and 93.24; those of the brightest cupping center were 174.84, 179.94, and 177.76; and those of the largest inferior retinal vein were 61.85, 53.48, and 56.73 for observers 1, 2, and 3, respectively. Inter-observer reproducibility for NR, BCC and IRV was considered good based upon ICC values of 0.944, 0.860, and 0.789 for observers 1, 2, and 3, respectively. Significant age-related differences between the values of the brightest cupping center were noted, and the gray scale score was decreased in the older participants (p < 0.001)., Conclusions: The gray scale of the brightest cupping center diminished with age. ImageJ can be a useful objective tool with high reproducibility in the analysis of optic disc color.

A 63-year-old man with a history of liver transplantation presented to our clinic complaining of visual disturbance. He had been receiving tacrolimus (FK 506) for 30 months (6 mg/day for 2 years and 3 mg/day for 6 months); he reported that the visual disturbance began while taking tacrolimus. A full ophthalmologic examination and electrophysiologic and imaging studies were performed. The best corrected visual acuity was 0.1 in both eyes. There were no abnormal finding in the anterior segment, pupillary reflexes were normal and, there was no swelling in either optic disc. Although the foveal reflex was slightly decreased, fluorescein angiography revealed non-specific signs, with the exception of a window defect. A multifocal electro-retinogram revealed decreased amplitude of the central ring. A Swedish interactive threshold algorithm-standard 10-2 visual field test revealed a central scotoma. These findings suggest that tacrolimus may result in maculopathy. Therefore, careful ophthalmologic examination is necessary in the patients taking tacrolimus.

Purpose: To investigate the clinical manifestations and diagnoses of optic disc swelling., Methods: The medical records of 49 patients who experienced optic disc swelling between March 2008 and June 2009 were retrospectively reviewed. The characteristics of non-arteritic anterior ischemic optic neuropathy (NA-AION) and optic neuritis (ON), which showed optic disc swelling most commonly, were compared., Results: NA-AION was the most common disorder (34.7%) that presented with optic disc swelling. ON was identified in 15 patients (30.6%). Seven out of 49 patients (14.3%) had intracranially associated diseases, such as papilledema and compressive optic neuropathy. Pseudopapilledema was noted in four patients (8.2%). Other diseases (e.g., papillophlebitis, neuroretinitis, and diabetic papillopathy) were seen in six patients (12.2%). Ocular pain was observed more commonly in patients with ON (p = 0.001). Patients with ON expected a better visual prognosis than patients with NA-AION (0.12 ± 0.32 vs. 0.49 ± 0.35, p = 0.001)., Conclusions: NA-AION and ON should be considered in the differential diagnosis when patients with optic disc swelling present to the neuro-ophthalmology clinic. Detailed history taking and supportive examinations, such as visual field, color-vision and imaging tests, should also be performed as indicated. Regular follow-up of such exams is necessary for the differential diagnosis of these diseases.

Purpose: To describe findings of spectral domain optical coherence tomography (SD-OCT) in the diagnosis of occult macular dystrophy (OMD)., Materials and Methods: Five visually disturbed patients who had shown normal findings in full field electroretinogram (ERG), fundus photography and fluorescein angiography but abnormal findings in multifocal ERG had undergone SD-OCT. The morphologic changes in retina and macular thickness were detected and imaged by SD-OCT. We analysed the results of SD-OCT including macular thickness, inner segment and outer segment (IS/OS) boundary and external limiting membrane (ELM)., Results: Mean age was 41.6 (22-63) in three male and two female patients in this study. Mean central foveal thickness was 142.9 (76-161) μm. All patients had shown decreased bowing of IS/OS boundary, and five of nine eyes were noted with disrupted IS/OS boundary of the photoreceptors according to SD-OCT. The interruption of external limiting membrane was noted in three of nine eyes., Conclusions: Spectral domain optical coherence tomography findings are useful in diagnosing OMD. Morphologic changes of the retina including deformity of the OS/IS boundary of the photoreceptors, disruption of the ELM and decreased foveal thickness may be important characteristics to consider when determining the pathophysiology and diagnosing criteria of OMD., (© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.)

In this case report, we describe a case of isolated oculomotor nerve palsy associated with antibodies to mitotic spindle apparatus (anti-MSA). A 28-year-old female patient had acute, painful vertical diplopia. She had limited depression and adduction in the right eye. There was no relative afferent pupillary defect. Brain magnetic resonance imaging showed no abnormal findings. Laboratory tests were all negative, with the exception of positive anti-MSA, She had an excellent and rapid response to treatment with corticosteroids, and completely recovered after two weeks of steroid pulse therapy.

Aim: To report a case of branch retinal artery obstruction (BRAO) complicated after anterior ischemic optic neuropathy (AION)., Methods: A 42 year-old woman who complained of visual disturbance was performed ophthalmological examinations such as fundus photography, fluorescent angiography (FAG) and visual field test., Results: At first visit, disc swelling was noted and arterial circulation was intact, however, 1 week after onset, the inferior branch retinal artery began to shrink and the flame hemorrhage intensified. Sixteen months later, the optic disc evidenced an atrophic change; additionally, a ghost vessel in the inferior branch retinal artery was found., Conclusion: We report a case of complications of BRAO arising after AION which caused the mechanical compression on the arterial circulation.

A 62-year-old woman has been suffered from cavernous sinus thrombophlebitis which was confirmed by four-vessel angiography, orbit magnetic resonance imaging, and blood culture. Three weeks after recovery of cavernous sinus thrombophlebitis, right eye proptosis and complete third, fourth, and sixth cranial nerve palsies developed. Best-corrected visual acuity decreased to 20/70 in the right eye. Repeat magnetic resonance imaging demonstrated a 1.5-cm-sized mass in the right cavernous sinus, suspicious for mycotic aneurysm. Amphotericin B supplementation was begun and was followed by successful transarterial Guglielmi detachable coil embolization. Four months later, extraocular movement was normalized, and visual acuity improved to 20/25 in the right eye.

Purpose: To evaluate the influence of H(2)O(2) on lens epithelial cells (LECs) and to determine the effect of the Janus kinase (JAK) inhibitor AG490 and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 on LEC death after H(2)O(2) exposure., Methods: Human lens epithelial (HLE) B-3 cells were cultured. Cells were treated for 45 min with H2O2 and signal transducers and activators transcription (STAT) 3, JAK2, and ERK1/2 phosphorylation were surveyed by Western blot analysis. After pretreatment with either 40 microM AG490 or 25 microM U0126, LECs were exposed to H(2)O(2). LEC death was evaluated by microscopy and flow cytometry., Results: H(2)O(2) induced phosphorylation of Tyr-705 STAT3, JAK2, and ERK1/2 in LECs. In cells pretreated with both AG490 and U0126, phosphorylation of Tyr-705 STAT3, JAK2, and ERK1/2 was suppressed. Microscopic findings, however, showed that only AG490 noticeably enhanced cell survival, and flow cytometry showed that cell necrosis decreased to 4.05% after pretreatment with 40 microM AG490., Conclusions: AG490 may prevent H(2)O(2)-induced LEC death by blocking an unknown necrosis pathway. Further investigation is required to characterize that pathway.

We report a case of one sister and brother with mirror image myopic anisometropia. One sister and brother complained visual disturbance. The sister was 10 years 11 months old, and brother was 8 years 4 months old. Full ophthalmic examinations were performed, including slit lamp examination, intraocular pressure, keratometry, anterior chamber depth, axial length, fundus examination and the cycloplegic refraction. The cycloplegic refractive power was -15.50 dpt cyl.+4.50 dpt Ax 85 degrees (right eye), -1.00 dpt cyl.+0.50 dpt Ax 90 degrees (left eye) in the sister; -1.75 dpt cyl.+2.25 dpt Ax 90 degrees (right eye), -9.50 dpt cyl.+4.00 dpt Ax 80 degrees (left eye) in the brother. The co-occurrence of severe myopic anisometropia in a sister and brother is extremely rare. The present case suggests that severe myopic anisometropia may be related by genetic inheritance.

A 46-year-old man presented with visual disturbances in both eyes. His best corrected visual acuity was 0.7 (both eyes). Ptosis and limitation of ocular movement in every direction were observed. Slit lamp examination showed a bilateral iridescent cataract. Fundus examination showed peripheral depigmentation of the retinal pigment epithelium and pigmentary clumping in both eyes that agreed with blocked fluorescence and widow defects on fluorescein angiography. The amplitude of b-wave was decreased on electroretinography. Fourteen months later, the patient's best corrected visual acuity decreased to 0.3 due to increased lens opacity. Phacoemulsification and intraocular lens implantation were performed on both eyes. At the patient's final visit, retinal findings were stable with a best corrected visual acuity of 0.7 in both eyes. In conclusion, the visual disturbance could have been caused by both cataracts and retinal degeneration, meaning the fundus should be examined carefully in patients with myotonic dystrophy.

Objective: The purpose of this study was to compare the sealing ability of an ultrasonically placed orthograde mineral trioxide aggregate (MTA) apical plug in open apices., Study Design: Thirty extracted human maxillary incisors were used. Experimental teeth were instrumented up to #100 file at the apex, and the 5 mm MTA apical barrier was placed with (group A; n = 11) or without (group B; n = 11) ultrasonic activation. Eight teeth served as control group. Bacterial leakage was assessed daily for 180 days using a double-chamber bacterial leakage model with Enterococcus faecalis. The results were analyzed with Fisher exact test., Results: After 60 days, the ratio of leaked samples showed significant difference between groups A (2 out of 10) and B (8 out of 11) (P < .05). The mean time elapsed before leakage showed significant difference between groups A (158 days) and B (23 days) (P < .05)., Conclusions: Ultrasonically placed orthograde MTA apical plugs were effective at delaying bacterial leakage.

Phenylalanine deletion at position 508 of the cystic fibrosis transmembrane conductance regulator (DeltaF508-CFTR), the most common mutation in cystic fibrosis (CF), causes a misfolded protein exhibiting partial chloride conductance and impaired trafficking to the plasma membrane. 4-Phenylbutyrate corrects defective DeltaF508-CFTR trafficking in vitro, but is not clinically efficacious. From a panel of short chain fatty acid derivatives, we showed that 2,2-dimethyl-butyrate (ST20) and alpha-methylhydrocinnamic acid (ST7), exhibiting high oral bioavailability and sustained plasma levels, correct the DeltaF508-CFTR defect. Pre-incubation (>or=6h) of CF IB3-1 airway cells with >or=1mM ST7 or ST20 restored the ability of 100microM forskolin to stimulate an (125)I(-) efflux. This efflux was fully inhibited by NPPB, DPC, or glibenclamide, suggesting mediation through CFTR. Partial inhibition by DIDS suggests possible contribution from an additional Cl(-) channel regulated by CFTR. Thus, ST7 and ST20 offer treatment potential for CF caused by the DeltaF508 mutation.

Objectives: Heat shock protein (HSP) can be utilized as a vaccine to cross-protect against multiple pathogenic species. The present study was performed to evaluate Porphyromonas gingivalis heat shock protein 60 (HSP60) as a vaccine candidate to inhibit multiple bacteria-induced alveolar bone loss., Material and Methods: Recombinant P. gingivalis HSP60 was produced and purified from P. gingivalis GroEL gene. Rats were immunized with P. gingivalis HSP60, and experimental alveolar bone loss was induced by infection with multiple periodontopathogenic bacteria., Results: There was a very strong inverse relationship between postimmune anti-P. gingivalis HSP immunoglobulin G (IgG) levels and the amount of alveolar bone loss induced by either P. gingivalis or multiple bacterial infection (p=0.007). Polymerase chain reaction data indicated that the vaccine successfully eradicated the multiple pathogenic species., Conclusions: We concluded that P. gingivalis HSP60 could potentially be developed as a vaccine to inhibit periodontal disease induced by multiple pathogenic bacteria.

Objective: Tuberculosis (TB) is an important opportunistic infection in HIV patients. Immune responses to Mycobacterium tuberculosis in HIV/TB patients were evaluated., Methods: Fifteen patients with HIV/TB, ten with HIV, four with TB, and five controls were enrolled. Peripheral blood mononuclear cells were isolated and stimulated with mycobacterial antigen (PPD). Interferon (IFN)-gamma and TNF-alpha in culture supernatants were measured by ELISA., Results: IFN-gamma and TNF-alpha production after PPD stimulation was markedly decreased in HIV patients, but not in HIV/TB patients. In HIV patients with a CD4 cell count of less than 200/mm3, IFN-gamma and TNF-alpha production after PPD stimulation was higher in HIV/TB patients than in HIV patients. Cytokine responses to M. tuberculosis reconstituted after highly active antiretroviral therapy (HAART) and were prominent in HIV/TB patients., Conclusions: Cytokine responses to M. tuberculosis were retained in HIV-infected patients with tuberculosis, even in patients with a CD4 cell count of less than 200/mm3, and reconstituted after HAART.

The present study has been performed to evaluate Porphyromonas gingivalis heat shock protein (HSP) 60 as a candidate vaccine to protect against multiple putative periodontopathic bacteria. Mouse anti-P. gingivalis HSP antisera demonstrated the elevated IgG antibody titers against the multiple bacteria tested and cross-reacted with heat-induced bacterial proteins of the target bacteria. The antisera also demonstrated a significantly higher opsonophagocytosis function against all the target bacteria than the control sera (P<0.01). We concluded that P. gingivalis HSP 60 could potentially be developed as a vaccine against multiple periodontopathic bacteria., (Copyright (c) Blackwell Munksgaard, 2005)

To identify T- and/or cross-reactive B-cell epitopes of P. gingivalis and human heat-shock protein (HSP)60 in atherosclerosis patients, we synthesized 104 overlapping synthetic peptides spanning whole molecules of P. gingivalis HSP60 and human HSP60, respectively. T-cell epitopes of P. gingivalis HSP were identified with the use of previously established P. gingivalis HSP-reactive T-cell lines. B-cell epitopes of P. gingivalis HSP60 and human HSP60 were identified by the use of patients' sera. Anti-P. gingivalis, anti-P. gingivalis HSP60, or anti-human HSP60 IgG antibody titers were higher in the atherosclerosis patients compared with the healthy subjects. Five immunodominant peptides of P. gingivalis HSP60, identified as T-cell epitopes, were also found to be B-cell epitopes. Moreover, 6 cross-reactive B-cell epitopes of human HSP60 were identified. It was concluded that P. gingivalis HSP60 might be involved in the immunoregulatory process of atherosclerosis, with common T- and/or B-cell epitope specificities and with cross-reactivity with human HSP60.

The heat shock proteins (hsp) of bacterial species are considered to be involved in regulating the autoimmune mechanism in human diseases due to the considerable homology of their sequences with human hsp. To elucidate how stress proteins contribute to the immunopathogenesis of periodontitis, mononuclear cells from gingival connective tissue of 10 periodontitis patients were simulated with Porphyromonas gingivalis hsp60. T-cell lines reactive to P. gingivalis hsp60 were established from each patient to define T-cell epitope specificities. Anti-P. gingivalis IgG antibody titres were elevated in all patients. We could establish P. gingivalis hsp-reactive T-cell lines from gingival mononuclear cells that were mixtures of CD4+ and CD8+ cells. Of 108 overlapping synthetic peptides spanning the whole P. gingivalis hsp60 molecule, 10 peptides with epitope specificities for T-cells were identified, and were identical to those reported be B-cell epitopes in periodontitis.

Mouse immune sera obtained by immunization with Fusobacterium nucleatum and then Porphyromonas gingivalis demonstrated an impaired binding capacity to P. gingivalis-biofilm and lower avidity to P. gingivalis when compared with sera obtained from mice immunized with P. gingivalis alone.

The incidence of tuberculosis in renal transplant patients has been reported to be fairly low and disseminated tuberculosis presenting with cutaneous manifestations has not been reported previously in these patients. We report the case of a 62-y-old kidney transplant recipient with a long-term history of chronic immunosuppressive therapy who presented with high fever, rapidly progressing respiratory failure and disseminated erythematous pustular cutaneous lesions.

Pancreatic duct epithelial cells (PDEC) mediate the exocrine secretion of fluid and electrolytes. We previously reported that ATP and UTP interact with P2Y(2) receptors on nontransformed canine PDEC to increase intracellular free Ca2+ concentration ([Ca2+](i)) and stimulate Ca2+-activated Cl- and K+ channels. We now report that ATP interacts with additional purinergic receptors to increase cAMP and activate Cl- channels. ATP, 2-methylthio-ATP, and ATP-gamma-S stimulated a 4- to 10-fold cAMP increase with EC(50) of 10-100 microM. Neither UTP nor adenosine stimulated a cAMP increase, excluding a role for P2Y(2) or P1 receptors. Although UTP stimulated an (125)I(-) efflux that was fully inhibited by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM), ATP stimulated a partially resistant efflux, suggesting activation of additional Cl- conductances through P2Y(2)-independent and Ca2+-independent pathways. In Ussing chambers, increased cAMP stimulated a much larger short-circuit current (I(sc)) increase from basolaterally permeabilized PDEC monolayers than increased [Ca2+](i). Luminal ATP and UTP and serosal UTP stimulated a small Ca2+-type I(sc) increase, whereas serosal ATP stimulated a large cAMP-type I(sc) response. Serosal ATP effect was inhibited by P2 receptor blockers and unaffected by BAPTA-AM, supporting ATP activation of Cl- conductances through P2 receptors and a Ca2+-independent pathway. RT-PCR confirmed the presence of P2Y(11) receptor mRNA, the only P2Y receptor acting via cAMP.

Short-term behavioral sensitization of the gill-withdrawal reflex after tail stimuli in Aplysia leads to an enhancement of the connections between sensory and motor neurons of this reflex. Both behavioral sensitization and enhancement of the connection between sensory and motor neurons are importantly mediated by serotonin. Serotonin activates two types of receptors in the sensory neurons, one of which is coupled to the cAMP/protein kinase A (PKA) pathway and the other to the inositol triphosphate/protein kinase C (PKC) pathway. Here we describe a genetic approach to assessing the isolated contribution of the PKA pathway to short-term facilitation. We have cloned from Aplysia an octopamine receptor gene, Ap oa(1), that couples selectively to the cAMP/PKA pathway. We have ectopically expressed this receptor in Aplysia sensory neurons of the pleural ganglia, where it is not normally expressed. Activation of this receptor by octopamine stimulates all four presynaptic events involved in short-term synaptic facilitation that are normally produced by serotonin: (i) membrane depolarization; (ii) increased membrane excitability; (iii) increased spike duration; and (iv) presynaptic facilitation. These results indicate that the cAMP/PKA pathway alone is sufficient to produce all the features of presynaptic facilitation.

To determine the frequency and types of major opportunistic diseases in patients with HIV infection in South Korea, we reviewed the medical records of 173 HIV-infected patients. The patients were seen from 1985 to 1998 at a referral hospital for AIDS in South Korea. Most patients (85%) were male, and 107 (62%) were infected by heterosexual contacts. CD4+ lymphocyte counts at presentation were <200/microL in 27% of the patients. Tuberculosis was the most frequent opportunistic infection (25% of patients), followed by candidiasis (21%), herpes zoster (20%), Pneumocystis carinii pneumonia (10%), cytomegalovirus disease (9.8%). There were no cases of toxoplasmosis. Kaposi's sarcoma developed in 3 patients (1.7%), and non-Hodgkin's lymphoma, in 2 (1.2%). Eleven patients (6.4%) developed peripheral neuropathy, and 8 (4.6%) had HIV encephalopathy. Tuberculosis was the single most important HIV-related infection in South Korean patients.

A cDNA clone encoding a muscarinic acetylcholine receptor (mAChR) has been isolated from the nematode Caenorhabditis elegans. The nematode mAChR, consisted of 585 amino acids, displays a high degree of amino acid sequence homology to other invertebrate and vertebrate mAChRs. Excluding a highly variable middle portion of the third intracellular loop, the C. elegans mAChR shares about 51% amino acid sequence identity with a Drosophila mAChR and 42-44% identity with human m1-m5 mAChR subtypes. Comparison of the cDNA sequence with the corresponding genomic sequence reveals that the C. elegans mAChR gene contains ten introns, eight of them in the coding region. Pharmacological profiles of the C. elegans mAChR expressed in Chinese hamster ovary (CHO) cells were shown to be similar to those of mammalian counterparts, indicating that ligand binding domains of the receptor have been conserved during evolution. When this cloned receptor was expressed in Xenopus oocytes, acetylcholine evoked a transient Cl- current. Furthermore, activation of the receptor with oxotremorine, acetylcholine or carbachol resulted in the stimulation of phosphatidylinositol metabolism in CHO cells, suggesting that the receptor is coupled to phospholipase C activation.

Interactions between the Escherichia coli primary replicative helicase DnaB protein and nucleotide cofactors have been studied using several fluorescent nucleotide analogs and unmodified nucleotides. The thermodynamically rigorous fluorescent titration technique has been used to obtain true binding isotherms, independently of the assumptions of any relationships between the observed quenching of protein fluorescence and the degree of nucleotide binding. Fluorescence titrations using several MANT derivatives of nucleoside diphosphates (MANT-ADP, 3',2'-O-(N-methylantraniloyl)adenosine-5'-diphosphate; MANT-GDP, 3',2'-O(N-methylantraniloyl)guanosine-5'-diphosphate; MANT-CDP, 3',2'-O-(N-methylantraniloyl)cytidine-5'-diphosphate; MANT-UDP, 3',2'-O-(N-methylantraniloyl)uridine-5'-diphosphate) have shown that the DnaB helicase has a preference for purine nucleotides. Binding of all modified nucleotides is characterized by similar negative cooperativity, indicating that negative cooperative interactions are base-independent. Thermodynamic parameters for the interactions of the unmodified nucleotides (ADP, GDP, CDP, and UDP) and inorganic phosphate (P(i)) have been obtained by using the competition titration approach. To analyze multiple ligand binding to a finite circular lattice, for a general case in which each lattice binding site can exist in different multiple states, we developed a matrix method approach to derive analytical expressions for the partition function and the average degree of binding for such cases. Application of the theory to competition titrations has allowed us to extract the intrinsic binding constants and cooperativity parameters for all unmodified ligands. This is the first quantitative estimate of affinities and the mechanisms of binding of different unmodified nucleotides and inorganic phosphate for a hexameric helicase. The intrinsic affinities of all of the studied ATP analogs are lower than the intrinsic affinities of the corresponding ADP analogs. The implications of these results for the mechanism of helicase action are discussed.

Quantitative analyses of the interactions of the Escherichia coli primary replicative helicase DnaB protein with single-stranded DNA have been performed using the thermodynamically rigorous fluorescence titration technique. This approach allowed us to obtain absolute stoichiometries of the formed complexes and interaction parameters, without any assumptions about the relationship between the observed signal change and the degree of binding. The analysis of the DnaB helicase interactions with nonfluorescent, unmodified nucleic acids has been performed, using a novel spectroscopic Macromolecular Competition Titration (MCT) method developed in the accompanying paper [Jezewska, M. J., & Bujalowski, W. (1996) Biochemistry 35, 2117-2128]. In the presence of the ATP nonhydrolyzable analog AMP-PNP, the DnaB helicase binds polymer DNA with a site-size of 20 +/- 3 nucleotides per protein hexamer. This site-size is independent of the type of nucleic acid base as well as the salt concentration and type of salt. Direct thermodynamic studies of the polynucleotide and oligomer binding to the DnaB hexamer, as well as the competition studies, show that independently of the type of nucleic acid base, as well as salt concentration and type of salt in solution, the helicase has only a single, strong binding site for DNA. Only this site is used when the protein interacts with polymer DNA. Moreover, UV photo-cross-linking experiments with oligonucleotides of different lengths, dT(pT)19, dT(pT)55, and dT(pT)69, suggest that primarily a single subunit of the DnaB helicase hexamer is in contact with the DNA. In interactions with polymer nucleic acids, the DnaB protein shows preferential intrinsic affinity for poly(dA), characterized in our standard conditions (pH 8.1, 10 degrees C, 100 mM NaCl, 5 mM MgCl2) by the intrinsic binding constant K = 6 +/- 2 x 10(6) M-1. These affinities are comparable to the affinities of the single-strand binding proteins in the corresponding solution conditions and strongly suggest that the helicase is capable of binding DNA without additional facilitating factors. Both the intrinsic affinity and the cooperativity are salt dependent. The formation of the DnaB-DNA complex is accompanied by the net release of approximately 2 ions, while another net release of approximately 2 ions accompanies the cooperative interactions. The data indicate an anion effect on the studied interactions and suggests that the released ions most probably originate from both the protein and the nucleic acid. The presence of a single, strong binding site on the hexamer, built of six chemically identical subunits, the very low site-size of the large helicase-DNA complex, and the involvement of a single subunit in contact with the nucleic acid indicate the presence of long-range allosteric interactions in the DnaB helicase which encompass the entire DnaB hexamer. Our sedimentation velocity measurements of the DnaB protein-(AMP-PNP)-5'-fluorescein-(dT)20 ternary complex show that the sedimentation coefficient of the complex is S20,W = 12.3 +/- 0.3, compared with S20,W = 10.5 +/- 0.3 of the free enzyme, indicating large changes in the hydrodynamic properties of the enzyme in the complex. These results provide direct evidence that the DnaB hexamer undergoes dramatic conformational changes which include all six subunits of the enzyme in the ternary complex. Moreover, sedimentation velocity studies of the ternary complex provide direct evidence that the hexamer is the species which binds ss nucleic acid. The significance of these results for a mechanistic model of the functioning of the DnaB helicase in DNA replication is discussed.

The value of the twist energy parameter (ET) of pBR322 is determined near zero superhelix density from topoisomer distributions created under various conditions. The resulting value, ET = 1155 +/- 65, at 37 degrees C is essentially unaffected by adding 10 mM Mg2+, or by changing the kind of Topo I from chicken-red-cell to calf-thymus. This value significantly exceeds that (ET = 950 +/- 80) measured for p30 delta DNA under identical conditions by the same method in the preceding paper. Decreasing the temperature from 37 to 21 degrees C yields a slightly larger value, ET = 1340 +/- 130, but the statistical significance of the increase is marginal. Attempts to determine reliable ET values for pBR322 at higher superhelix densities by ethidium binding were frustrated by the fact that good fits of the equilibrium dialysis results could not be achieved using a single value of ET. Moreover, the curves of apparent ET versus binding ratio r vary considerably from one preparation to another, and for a given preparation vary with time after cell lysis up to about seven weeks, after which they settle in to nearly reproducible behavior. The apparent ET values obtained from competitive dialysis experiments are typically rather low (ET approximately 700) for small r and nearly native superhelix density, and rise up to 1300 to 1500 with increasing binding ratio (up to r = 0.055) and decreasing negative superhelix density.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of inserting 16 base pair (bp) of alternating CG [(CG)8] near the middle of a much longer restriction fragment (1097 bp) are investigated by measuring various properties that are sensitive to secondary and tertiary structure. Results for this fragment are compared with those for a control fragment (1089 bp) with the identical sequence except at the insert. Another fragment (1382 bp), which contains a 296-bp extension at the 5'-end of the 1089-bp control fragment, is also used as a secondary control in some experiments. When the 1097-bp (CG)8 insert fragment is compared with the control fragments in 0.1 M NaCl buffer, the (CG)8 insert is found to induce disproportionately large relative changes in the molar ellipticity at 273 nm ([theta]273), the torsion constant (alpha) measured by fluorescence polarization anisotropy, the optical melting profile, and the susceptibility to S1 nuclease. Estimates of the minimum distance over which the (CG)8 insert alters the secondary structure range from 330 to 550 bp. With increasing NaCl concentration, the 1097-bp insert fragment undergoes a structural transition between 2.0 and 2.5 M that is manifested in the apparent diffusion coefficient (Dplat) from dynamic light scattering at large scattering vector. This transition, which is not exhibited by the control DNAs, is presumed to involve formation of Z-helix at the insert. However, the observed decrease in (Dplat) is attributed to an increase in bending rigidity, which perforce must be globally distributed far beyond the (CG)8 insert per se. In 4.25 M NaCl (but not in 0.1 M NaCl), the addition of 1 ethidium dye per 300 bp induces an extensive structural transition in the 1097 bp (CG)8 insert fragment. This transition, which also is not exhibited by the control DNAs, significantly decreases the bending rigidity, doubles [theta]273, and takes place on a time scale of a few days. Removal of ethidium and salt by dialysis vs 0.1 M NaCl buffer restores the original properties of the 1097-bp (CG)8 insert fragment. The present results are consistent with a (fluctuating, long-range) description of the secondary structure in which a given short sequence transiently fluctuates among two or more distinct secondary structures that extend over much larger domains of variable position and size, and whose relative stabilities depend on distant as well as close-lying base pairs.

A patient with von Recklinghausen's disease manifested by dermal neurofibromatosis and cafe-au-lait spots presented with complaints of malaise, weight loss, lower extremity weakness, and a palpable left lower abdominal quadrant mass. Evaluation revealed a lumbar neurofibroma, a localized primary carcinoid tumor of the mesentery, and a left renal angiomyolipoma. Although an association between neurofibromatosis and carcinoid has been previously reported, we believe this is the first report documenting the association of all three entities.