[Characteristics of primary ocular symptoms in children with optic pathway glioma at different ages].

Objective: To investigate the characteristics of initial ocular symptoms in children with optic pathway glioma (OPG) at different age stages. Methods: A retrospective case series study was conducted. Clinical data of 16 children with OPG who were diagnosed and treated in the Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University from April 2017 to July 2021 were collected. The initial ocular symptoms, clinical manifestations of the eyes and nervous system, imaging and histopathological features were analyzed, and the differences in initial ocular symptoms between infants and young children aged≤36 months and older children aged>36 months were compared. Results: Of all 16 children included, 9 were male and 7 were female. The onset age was 15.0 (6.3, 56.5) months, and the diagnosis age was 48.0 (11.3, 78.0) months. There were 11 infants and young children, and 5 older children. Eye symptoms were the initial manifestation in 11 cases, including 8 cases of infants and young children (5 cases presented with irregular nystagmus, 2 cases with strabismus, and 1 case with failure to chase visual target), and 3 cases of older children (2 cases presented with decreased vision and 1 case with optic disc edema). The imaging findings showed that optic chiasm-involved OPG accounted for the highest proportion, with 3 cases in older children and 8 cases in infants and young children. Among the 8 children with optic chiasm-involved OPG who underwent surgical treatment, 5 were diagnosed with pilocytic astrocytoma according to histopathological results. Seven children had useful vision saved after treatment, and 1 child had visual loss accompanied by cognitive impairment due to surgery after 4 years of nystagmus. Conclusion: OPG in children often manifests as initial ocular symptoms, with irregular nystagmus being more common in infants and young children, and vision loss being the main symptom in older children.

[Reconstruction of facial skin defects by the V-Y subcutaneous pedicle flap].

Objective: To investigate the method and efficacy of reconstruction of facial skin defects after removing the lesions by applying the V-Y subcutaneous pedicle flap. Methods: A retrospective analysis was performed on 23 patients with facial reconstruction by using V-Y subcutaneous pedicle flap in the Otolaryngology Department of Guangdong Integrated Traditional Chinese and Western Medicine Hospital from March 2012 to April 2021. Patient ages ranged from 45 to 85 years old, with a mean age of 66.5 years (14 males and 9 females). The facial lesion sites included cheek in 12 cases (nearly lower eyelid in 4 cases), nose in 4 cases, lips in 3 cases, temporal in 2 cases and mental region in 2 cases. The initial pathology included malignant tumors (7 cases of basal cell carcinoma (BCC), 2 cases of squamous cell carcinoma(SCC), and 1 case of malignant melanoma) and benign lesions (7 cases of keratoderma, 3 cases of intradermal nevus, 1 case of pilomatricoma, 1 case of cutaneous mixed tumor and 1 case of epidermal cyst). The V-Y subcutaneous facial pedicled flaps were designed reasonably after the facial lesions were excised. The advantages of blood supply, survival rate and adverse events of the flap were analyzed Chi-square test was used to compare the observation results of different types of patients. Results: The primary focus of 23 patients was excised surgically, and intraoperative frozen-section examinations were performed for obtaining margins negative as far as possible. One positive margin was still found in 1 patient after multiple resection in our group. The defect sizes were 14 mm×12 mm-59 mm×54 mm. All the flaps survived. The adverse events were slight necrosis of the epidermis at the junction or vicinity of the three arms of "Y" shaped in 4 cases, but the wounds finally recovered by wet compress and dressing change. There were no significant differences in the incidences of adverse events between double and single pedicle flaps (4/19 vs. 0/4), between benign and malignant lesions (4/13 vs. 0/10), and between patients with and without underlying diseases (1/6 vs. 3/17) (χ2 values were 0.98, 3.56, 0.01, respectively, all P>0.05). There were no other major complications such as dehiscence, hematoma, eyelid ectropion and lip deformation. The patients with benign lesions were followed-up at least for 3 months, while those with malignant tumors were followed-up for 6-36 months postoperatively, without recurrence. Conclusions: V-Y subcutaneous facial pedicled skin flap may be a "no-easy-necrotic" local flap in the repair of small and medium-sized facial defects.

[Vision-and health-related quality of life in patients with uveitis].

OBJECTIVE: To evaluate vision-and health-related quality of life in patients with uveitis, and to evaluate the relationship between quality of life and visual acuity. METHODS: Cross-sectional study. One hundred and eleven patients with uveitis were enrolled in the study from January 1, 2013 to April 1, 2014 in Peking University First Hospital. Clinical data collected included medical history, complete ophthalmologic examination and best corrected visual acuity (LogMAR). Basic clinical data (gender, diagnosis, etc.) was also collected. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and the 36-Item Short Form Health Survey (SF-36) were administered. The patients were divided into two groups, anterior uveitis group (ATU), and other types of uveitis in this study (OTU). T-test was used for analysis of the data which obey standard normal distribution, otherwise rank sum test was used for data analysis. Correlation and Linear regression were constructed between bilateral visual acuity and the scores of NEI VFQ-25 and SF-36 questionnaires. RESULTS: For all the 111 cases included in this study, 87 (78.4%) of them were anterior uveitis (ATU), 5 of them were intermediate uveitis, 7 of them were posterior uveitis and 12 of them were pan uveitis. Mean visual acuity of better and worse eye were 0.0 and 0.2 in ATU patients, respectively. Mean visual acuity of better and worse eye were 0.1 and 0.4 in OTU patients, respectively. Patients rated the general health subscale score of NEI VFQ-25 and SF-36 lower than other subscales, respectively (score of general health was 25.0 (25.0-50.0) in NEI VFQ-25 and 46.8 (19.8) in SF-36). ATU group scored higher that OTU group (Mean score of SF-36 was 77.5 (10.7) and 68.8 (16.9) in ATU and OTU group respectively, P value of SF-36< 0.01, t=9.54. Mean score of NEI VFQ-25 was 77.3 (12.8) and 59.1 (16.5) in ATU and OTU group respectively, P value of NEI VFQ-25<0.01, t=33.16). Mean score of NEI VFQ-25 of all patients was 73.4 (15.5). Mean visual acuity of better eye and worse eye of all patients were 0.0 (-0.2-1.0) and 0.3 (0.5), respectively. The correlation coefficient was -0.497 (P<0.01, t=-5.98) between NEI VFQ -25 score and visual acuity in better eye, and -0.32 (t=-3.48, P<0.01) between NEI VFQ-25 score and visual acuity in worse eye. The coefficient was -3.9 in linear regression of visual acuity in better eye against NEI VFQ-25 score (t=-5.98, P<0.01), and -1.1 of visual acuity in worse eye against NEI VFQ-25 score (t=-3.48,P<0.01). CONCLUSIONS: General health was more affected than other function subscales in uveitis. The quality of life in anterior uveitis was higher than other types of uveitis in this study. Vision-related quality of life correlated with both eyes.(Chin J Ophthalmol, 2016, 52: 429-436).

A strong red-emitting carbazole based europium(III) complex excited by blue light.

A novel 2-positional linked carbazole based ß-diketone with methoxyl in the 7-position (EMOCTFBD), and its europium(III) ternary complex Eu(EMOCTFBD)(3)phen were synthesized via a dexterously designed indirect routine, where EMOCTFBD was 1-(9-ethyl-7-methoxyl-9H-carbazol-2-yl)-4,4,4-trifluorobutane-1,3-dione and phen was 1,10-phenanthroline. Eu(EMOCTFBD)(3)phen shows high thermal stability. The introduction of a methoxyl in the 7-position of the carbazole ring remarkably enhanced the excitation band intensity in the blue region, and the complex exhibited intense red emission under blue-light excitation. The lowest triplet state energy was measured and suggests the photoluminescence process as a ligand-sensitized luminescence process (antenna effect). A bright red-emitting diode was fabricated by coating the complex phosphor onto a ∼460 nm-emitting InGaN chip. All the results indicate that Eu(EMOCTFBD)(3)phen is an interesting red-emitting material excited by blue light, and therefore may be applied in many fields without UV radiation.

Improvement of schizophrenic symptoms and changes in plasma HVA concentrations, plasma anti-D2 and anti-5-HT2 receptor activities with clozapine.

In order to investigate the biological mechanisms underlying the clinical efficacy of clozapine, 200 mg/day of clozapine was added to the drug regimens of 19 patients with chronic, anti-psychotic-resistant schizophrenia, and the plasma homovanillic acid (HVA), clozapine concentrations, anti-dopamine D2 and anti-serotonin 5-HT2 receptor activities were measured. After 28 days, six patients showed an improvement of more than 20% over baseline Brief Psychiatric Rating Scale (BPRS) scores. Mean plasma HVA concentrations and anti-D2 receptor activities did not change significantly in the entire group or in the six patients showing improvement. However, anti-5-HT2 receptor activities increased significantly in all 19 patients. Changes in BPRS scores did not correlate significantly with changes in plasma HVA or with changes in clozapine concentrations, or with anti-D2 and anti-5-HT2 receptor activities.

Mechanism of adenylate kinase. Demonstration of a functional relationship between aspartate 93 and Mg2+ by site-directed mutagenesis and proton, phosphorus-31, and magnesium-25 NMR.

Earlier magnetic resonance studies suggested no direct interaction between Mg2+ ions and adenylate kinase (AK) in the AK.MgATP (adenosine 5'-triphosphate) complex. However, recent NMR studies concluded that the carboxylate of aspartate 119 accepts a hydrogen bond from a water ligand of the bound Mg2+ ion in the muscle AK.MgATP complex [Fry, D.C., Kuby, S.A., & Mildvan, A.S. (1985) Biochemistry 24, 4680-4694]. On the other hand, in the 2.6-A crystal structure of the yeast AK.MgAP5A [P1,P5-bis(5'-adenosyl)pentaphosphate] complex, the Mg2+ ion is in proximity to aspartate 93 [Egner, U., Tomasselli, A.G., & Schulz, G.E. (1987) J. Mol. Biol. 195, 649-658]. Substitution of Asp-93 with alanine resulted in no change in dissociation constants, 4-fold increases in Km, and a 650-fold decrease in kcat. Notable changes have been observed in the chemical shifts of the aromatic protons of histidine 36 and a few other aromatic residues. However, the results of detailed analyses of the free enzymes and the AK.MgAP5A complexes by one- and two-dimensional NMR suggested that the changes are due to localized perturbations. Thus it is concluded that Asp-93 stabilizes the transition state by ca. 3.9 kcal/mol. The next question is how. Since proton NMR results indicated that binding of Mg2+ to the AK.AP5A complex induces some changes in the proton NMR signals of WT but not those of D93A, the functional role of Asp-93 should be in binding to Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of adenylate kinase. Critical evaluation of the X-ray model and assignment of the AMP site.

The substrate binding sites of adenylate kinase (AK) proposed by X-ray crystallographic studies [Pai, E. F., Sachsenheimer, W., Schirmer, R. H., & Schulz, G. E. (1977) J. Mol. Biol. 114, 37-45, and subsequent revisions] were evaluated by site-specific mutagenesis in conjunction with structural analysis by NMR. The residues examined in this report include two near an adenosine site (threonine-39 and arginine-44) and two in the phosphate binding region (arginine-128 and arginine-149). The results and conclusions are summarized as follows: (a) Although Thr-39 is very close to an adenine site [Egner, U., Tomasselli, A. G., & Schulz, G. E. (1987) J. Mol. Biol. 195, 649-658], it is nonessential either structurally or functionally. (b) The R44M mutant enzyme showed significant increases in the Michaelis and dissociation constants of adenosine 5'-monophosphate (AMP) (36- and 22-fold, respectively) while all other kinetic parameters were relatively unperturbed. The proton NMR property of this mutant was unchanged in the free enzyme and only slightly perturbed in the binary complexes with AMP and with MgATP (adenosine 5'-triphosphate), and in the ternary complex with MgAP5A [P1,P5-bis(5'-adenosyl) pentaphosphate]. These results indicate that Arg-44 interacts specifically with AMP starting at the binary complex, and suggest that the MgATP site proposed by Pai et al. (1977) is likely to be the AMP site. (c) The kinetic parameters of R149M were dramatically perturbed: kcat decreased by a factor of 1540, Km increased to 130-fold, and kcat/Km decreased by a factor of 2 X 10(5).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of adenylate kinase. Structural and functional demonstration of arginine-138 as a key catalytic residue that cannot be replaced by lysine.

Replacement of the arginine-138 of adenylate kinase (AK) by lysine or methionine resulted in a decrease in kcat by a factor of 10(4), increases in Km by a factor of 10-20, and relatively little changes in dissociation constants. Proton nuclear magnetic resonance (NMR) studies were then undertaken to obtain structural information for quantitative interpretation of the kinetic data. Since the lysine mutant (R138K) represents a conservative mutation with surprisingly large effects on kinetics, structural studies were focused on the wild type (WT) and R138K. The results and conclusions are summarized as follows: (i) The aromatic spin systems of WT and R138K were assigned from total correlated spectroscopy (TOCSY). Comparison of the chemical shifts of aromatic protons, one-dimensional spectra, TOCSY, and nuclear Overhauser enhanced spectroscopy (NOESY) indicated that the conformation of R138K was almost unperturbed relative to that of WT. Thus Arg-138 is not important for the tertiary structure. (ii) Proton NMR titrations with AMP and MgATP suggested that substrate binding affinities and substrate-induced conformational changes are nearly identical between WT and R138K. Thus arginine-138 should not be involved in stabilizing the first substrate in the binary complex. (iii) Notable differences were observed between the proton NMR spectra of the WT and R138K complexes with the reaction mixture, which agrees with the perturbation in the Km values of R138K. The differences were analyzed in detail by using a "static reaction mixture'--p1, p5-bis(5'-adenosyl)pentaphosphate (MgAP5A). The aromatic spin systems of WT + MgAP5A and R138K + MgAP5A were partially assigned from various two-dimensional spectra.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of adenylate kinase. Are the essential lysines essential?

Using site-specific mutagenesis, we have probed the structural and functional roles of lysine-21 and lysine-27 of adenylate kinase (AK) from chicken muscle expressed in Escherichia coli. The two residues were chosen since according to the nuclear magnetic resonance (NMR) model [Mildvan, A. S., & Fry, D. C. (1987) Adv. Enzymol. 58, 241-313], they are located near the alpha- and the gamma-phosphates, respectively, of adenosine 5'-triphosphate (ATP) in the AK-MgATP complex. In addition, a lysine residue (Lys-21 in the case of AK) along with a glycine-rich loop is considered "essential" in the catalysis of kinases and other nucleotide binding proteins. The Lys-27 to methionine (K27M) mutant showed only slight increases in kcat and Km, but a substantial increase (1.8 kcal/mol) in the free energy of unfolding, relative to the WT AK. For proper interpretation of the steady-state kinetic data, viscosity-dependent kinetics was used to show that the chemical step is partially rate-limiting in the catalysis of AK. Computer modeling suggested that the folded form of K27M could gain stability (relative to the wild type) via hydrophobic interactions of Met-27 with Val-179 and Phe-183 and/or formation of a charge-transfer complex between Met-27 and Phe-183. The latter was supported by an upfield shift of the methyl protons of Met-27 in 1H NMR. Other than this, the 1H NMR spectrum of K27M is very similar to that of WT, suggesting little perturbation in the global or even local conformations.(ABSTRACT TRUNCATED AT 250 WORDS)