Direct Detection of Thrombin Binding to 8-Bromodeoxyguanosine-Modified Aptamer: Effects of Modification on Affinity and Kinetics

The affinity of an 8-bromodeoxyguanosine- (8-BrdG-) substituted thrombin-binding aptamer (TBA-Br), which has the 1st and 10th guanosine residues replaced with 8-BrdG, was estimated using reflectometric interference spectroscopy (RIfS). When comparing TBA-Br with unmodified TBA (TBA-H), it was demonstrated that the modification effectively improved the affinity of TBA; dissociation constants (KD) of TBA-H and TBA-Br were 45.4 nM and 1.99 nM, respectively. These values, which were obtained by direct observation of thrombin binding using RIfS, have the same order of magnitude as those obtained in our previous study utilizing conformational changes in TBA to detect thrombin binding, thus confirming the validity of the obtained KD values. RIfS measurements also revealed that the 8-BrdG modification resulted in a lower dissociation rate constant (kd), which suggests that the enhancement of affinity can be attributed to the stabilization of the G-quadruplex structure on introduction of 8-BrdG

Genetics and Genomics of Congenital diseases

Virtually any disease is the result of the combined action of genes and environment, but the relative role of the genetic component may be large or small. Among disorders caused wholly or partly by genetic factors, three main types are recognized : chromosome disorder, single-gene defect, multifactorial disease with complex inheritance. In chromosome disorders, the defect is due to an excess or deficiency of genes located on entire chromosomes or chromosome segments. Single-gene defects are caused by pathogenic mutations in individual genes. The mutation may be present on both chromosomes of a pair or on only one chromosome of a pair. Single-gene defects often cause diseases that follow one of the classic inheritance patterns in families, autosomal recessive, autosomal dominant, or X-linked. Most such defects are rare, but single-gene disorders as a group are responsible for a significant proportion of disease and death. Multifactorial disease with complex inheritance describes the majority of diseases in which there is a genetic contribution, as evidenced by increased risk for disease in identical twins or close relatives of affected individuals, and yet the family history does not fit the inheritance patterns seen typically in single-gene defects. There appears to be no single error in the genetic information in many of these condition. Genetic counselors define and address the complex psychosocial issues associated with a genetic disorder in a family and provide psychologically oriented counseling to help individuals adapt and adjust to impact and implications of the disorder in the family. For this reason, genetic counseling may be most effectively accomplish through periodic contact with the family. In this article, I describe how genetics and genomics are applied to medical today

Macular Retinal Ganglion Cell Complex Thickness and Its Relationship to the Optic Nerve Head Topography in Glaucomatous Eyes with Hemifield Defects

Purpose. To evaluate the relationship between the macular ganglion cell complex (mGCC) thickness, which is the sum of the retinal nerve fiber, ganglion cell, and inner plexiform layers, measured with a spectral-domain optical coherence tomograph and the optic nerve head topography measured with a confocal scanning laser ophthalmoscope in glaucomatous eyes with visual field defects localized predominantly to either hemifield. Materials and Methods. The correlation between the mGCC thickness in hemispheres corresponding to hemifields with and without defects (damaged and intact hemispheres, respectively) and the optic nerve head topography corresponding to the respective hemispheres was evaluated in 18 glaucomatous eyes. Results. The mGCC thickness was significantly correlated with the rim volume, mean retinal nerve fiber layer thickness, and cross-sectional area of the retinal nerve fiber layer in both the intact and the damaged hemispheres (P < .05). Discussion. For detecting very early glaucomatous damage of the optic nerve, changes in the thicknesses of the inner retina in the macular area and peripapillary RNFL as well as rim volume changes in the optic nerve head are target parameters that should be carefully monitored

Ocular hypotensive effect, preservation of visual fields, and safety of adding dorzolamide to prostaglandin therapy for twelve months

Kenji Inoue1,3, Mieko Masumoto1,3, Masato Wakakura1, Goji Tomita2, On behalf of the Ochanomizu Ophthalmology Study Group31Inouye Eye Hospital, Tokyo, Japan; 2Department of Ophthalmology, Toho University School of Medicine, Tokyo, Japan; 3Ochanomizu Ophthalmology, Tokyo, JapanPurpose: To prospectively evaluate the safety, hypotensive effect, and preservation of visual fields of dorzolamide when added to latanoprost.Subjects and methods: This study included 46 patients (46 eyes) with primary open-angle glaucoma who had been treated with latanoprost. Dorzolamide (1%) was added to latanoprost, and the intraocular pressure (IOP) was monitored before and after 3, 6, and 12 months. The mean deviation shown by Humphrey perimetry was compared before and after twelve months of treatment. Adverse reactions were monitored over the 12-month study period.Results: The mean baseline IOP was 17.2 &amp;plusmn; 3.0 mmHg while those after 3, 6 and 12 months of treatment were 14.9 &amp;plusmn; 3.0 mmHg, 14.5 &amp;plusmn; 3.2 mmHg, and 14.6 &amp;plusmn; 2.6 mmHg respectively (P &amp;lt; 0.0001, 1-&amp;szlig;(power) = 0.9999571). The absolute reduction of IOP and the percent reduction were similar after 3, 6, and 12 months of treatment. The mean deviation on Humphrey perimetry was similar before and after twelve months of treatment. Three patients discontinued dorzolamide therapy due to elevation of IOP and one patient discontinued it because of adverse reactions.Conclusion: Dorzolamide is safe and effective when used for twelve months as add-on therapy to latanoprost for open-angle glaucoma.Keywords: dorzolamide, primary open-angle glaucoma, latanoprost&amp;nbsp

Tibial condylar valgus osteotomy (TCVO) for osteoarthritis of the knee: 5-year clinical and radiological results

According to one line of thought only propositions can be part of one’s evidence, since only propositions can serve the central functions of our ordinary concept of evidence. Ram Neta has challenged this argument. In this paper I respond to Neta’s challenge

A case of generalized lymphatic anomaly causing skull-base leakage and bacterial meningitis

Generalized lymphatic anomaly (GLA) is a multifocal lymphatic malformation that affects the skin, thoracic viscera, and bones. A 7-year-old boy presented with fever and disturbance of consciousness, and bacterial meningitis was diagnosed. Computed tomography and magnetic resonance imaging revealed middle skull-base leakage due to lymphatic malformation. Past history included facial palsy due to cystic tumors in the right petrous bone 4 years before onset of meningitis. At that time, pericardial effusion had been found and GLA had been diagnosed by pericardial biopsy. He achieved complete recovery under intensive care with antibiotics and mechanical ventilation. At the 3-year follow-up, the patient was healthy with no recurrence of meningitis. We should consider GLA among the differential diagnoses for osteolytic diseases in the pediatric population

Iris and periocular adverse reactions to bimatoprost in Japanese patients with glaucoma or ocular hypertension

Kenji Inoue1, Minako Shiokawa1, Michitaka Sugahara1, Risako Higa1, Masato Wakakura1, Goji Tomita21Inouye Eye Hospital, Tokyo, Japan; 2Second Department of Ophthalmology, Toho University School of Medicine, Tokyo, JapanPurpose: To prospectively investigate adverse reactions to bimatoprost in Japanese patients with glaucoma or ocular hypertension. We also examined patient attitudes to adverse reactions via a questionnaire.Methods: Fifty-two Japanese patients with glaucoma or ocular hypertension were enrolled. Iridial, eyelid, and eyelash photographs were taken before and at 6 months after bimatoprost treatment. Increase in eyelid pigmentation, iridial pigmentation, eyelash growth and bristle, and vellus hair of the lid was assessed from the photographs. Questionnaires completed by patients provided insight into their subjective judgment of adverse reactions.Results: Increase in eyelash bristle (53.8%), iris pigmentation (50.0%), eyelash growth (46.2%), vellus hair of the lid (40.4%), and eyelid pigmentation (7.7%) was evident after bimatoprost treatment. The objective and subjective assessments were in agreement in terms of increase in eyelash bristle, eyelash growth, and increase in vellus hair of the lid.Conclusion: Most patients were conscious of these adverse reactions. Before administering bimatoprost, sufficient explanation of potential adverse reactions should be provided; after initiating treatment, careful observation is required.Keywords: bimatoprost, adverse reaction, eyelid pigmentation, changes in eyelashes, iris pigmentation&amp;nbsp