Stem cell-derived paracrine factors by modulated reactive oxygen species to enhance cancer immunotherapy.

Herein, we present an approach for manipulating paracrine factors and signaling pathways in adipose-derived stem cells (ADSCs) to achieve highly effective tumor immunotherapy. Our method involves precise control of reactive oxygen species concentration using the CD90-maleimide-pluronic F68-chlorin e6 conjugate (CPFC) to create ACPFC, which is then attached to ADSCs through the CD90 receptor-specific interaction. By regulating the irradiated laser power, ACPFC promotes signaling pathways such as cascade-3, VEGFR2, α2ß1, C3AR1, CR1-4, and C5AR1, leading to the secretion of various inflammatory cytokines such as IFN-γ, TGF-ß, and IL-6, while inhibiting AKT, ERK, NFkB, PAR1, and PAR3/4 signaling pathways to reduce the secretion of cell growth factors like TIMP-1, TIMP-2, VEGF, Ang-2, FGF-2, and HGF. When ACPFC is injected intravenously into a tumor animal model, it autonomously targets and accumulates at the tumor site, and upon laser irradiation, it generates various anti-inflammatory factors while reducing angiogenesis growth factors. The resulting antitumor response recruits CD3+CD8+ cytotoxic T cells and CD3+CD4+ helper T cells into the tumor and spleen, leading to highly effective melanoma and pancreatic tumor treatment in mice. Our technology for regulating stem cell paracrine factors holds significant promise for the treatment of various diseases.

Distributed Authentication Model for Secure Network Connectivity in Network Separation Technology.

Considering the increasing scale and severity of damage from recent cybersecurity incidents, the need for fundamental solutions to external security threats has increased. Hence, network separation technology has been designed to stop the leakage of information by separating business computing networks from the Internet. However, security accidents have been continuously occurring, owing to the degradation of data transmission latency performance between the networks, decreasing the convenience and usability of the work environment. In a conventional centralized network connection concept, a problem occurs because if either usability or security is strengthened, the other is weakened. In this study, we proposed a distributed authentication mechanism for secure network connectivity (DAM4SNC) technology in a distributed network environment that requires security and latency performance simultaneously to overcome the trade-off limitations of existing technology. By communicating with separated networks based on the authentication between distributed nodes, the inefficiency of conventional centralized network connection solutions is overcome. Moreover, the security is enhanced through periodic authentication of the distributed nodes and differentiation of the certification levels. As a result of the experiment, the relative efficiency of the proposed scheme (REP) was about 420% or more in all cases.

V-Set and Immunoglobulin Domain-Containing 1 (VSIG1), Predominantly Expressed in Testicular Germ Cells, Is Dispensable for Spermatogenesis and Male Fertility in Mice.

To elucidate the functional role of V-set and immunoglobulin domain-containing 1 (VSIG1) in spermatogenesis and fertilization, we knocked out (KO) VSIG1 in a mouse embryo using CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9) -mediated genome editing. Reverse transcription PCR was performed using cDNA synthesized from VSIG1 KO testis RNA. Although Western blot analysis using a specific antibody to VSIG1 confirmed VSIG1 protein defects in the KO mice, hematoxylin-eosin staining analysis was similar in the KO and wild-type mice. Additionally, computer-assisted sperm analysis and in vitro fertilization experiments were conducted to confirm the activity and fertilization ability of sperm derived from the KO mouse. Mice lacking VSIG1 were viable and had no serious developmental defects. As they got older, the KO mice showed slightly higher weight loss, male mice lacking VSIG1 had functional testes, including normal sperm number and motility, and both male and female mice lacking VSIG1 were fertile. Our results from VSIG1 KO mice suggest that VSIG1 may not play essential roles in spermatogenesis and normal testis development, function, and maintenance. VSIG1 in sperm is dispensable for spermatogenesis and male fertility in mice. As several genes are known to possess slightly different functions depending on the species, the importance and molecular mechanism of VSIG1 in tissues of other species needs further investigation.

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome.

We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aß peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aß42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aß40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aß42/Aß40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1).

Gene-wise association of variants in four lysosomal storage disorder genes in neuropathologically confirmed Lewy body disease.

OBJECTIVE: Variants in GBA are associated with Lewy Body (LB) pathology. We investigated whether variants in other lysosomal storage disorder (LSD) genes also contribute to disease pathogenesis. METHODS: We performed a genetic analysis of four LSD genes including GBA, HEXA, SMPD1, and MCOLN1 in 231 brain autopsies. Brain autopsies included neuropathologically defined LBD without Alzheimer Disease (AD) changes (n = 59), AD without significant LB pathology (n = 71), Alzheimer disease and lewy body variant (ADLBV) (n = 68), and control brains without LB or AD neuropathology (n = 33). Sequencing of HEXA, SMPD1, MCOLN1 and GBA followed by 'gene wise' genetic association analysis was performed. To determine the functional effect, a biochemical analysis of GBA in a subset of brains was also performed. GCase activity was measured in a subset of brain samples (n = 64) that included LBD brains, with or without GBA mutations, and control brains. A lipidomic analysis was also performed in brain autopsies (n = 67) which included LBD (n = 34), ADLBV (n = 3), AD (n = 4), PD (n = 9) and control brains (n = 17), comparing GBA mutation carriers to non-carriers. RESULTS: In a 'gene-wise' analysis, variants in GBA, SMPD1 and MCOLN1 were significantly associated with LB pathology (p range: 0.03-4.14 x10(-5)). Overall, the mean levels of GCase activity were significantly lower in GBA mutation carriers compared to non-carriers (p<0.001). A significant increase and accumulation of several species for the lipid classes, ceramides and sphingolipids, was observed in LBD brains carrying GBA mutations compared to controls (p range: p<0.05-p<0.01). INTERPRETATION: Our study indicates that variants in GBA, SMPD1 and MCOLN1 are associated with LB pathology. Biochemical data comparing GBA mutation carrier to non-carriers support these findings, which have important implications for biomarker development and therapeutic strategies.

Association of weekend continuity of care with hospital length of stay.

OBJECTIVE: The purpose of this study was to evaluate the association of physician continuity of care with length of stay, likelihood of weekend discharge, in-hospital mortality and 30-day readmission. DESIGN: A cohort study of hospitalized medical patients. The primary exposure was the weekend usual provider continuity (UPC) over the initial weekend of care. This metric was adapted from an outpatient continuity of care index. Regression models were developed to determine the association between UPC and outcomes. SETTING: An academic medical center. MAIN OUTCOME MEASURE: Length of stay which was calculated as the number of days from the first Saturday of the hospitalization to the day of discharge. RESULTS: Of the 3391 patients included in this study, the prevalence of low, moderate and high UPC for the initial weekend of hospitalization was 58.7, 22.3 and 19.1%, respectively. When compared with low continuity of care, both moderate and high continuity of care were associated with reduced length of stay, with adjusted rate ratios of 0.92 (95% CI 0.86-1.00) and 0.64 (95% CI 0.53-0.76), respectively. High continuity of care was associated with likelihood of weekend discharge (adjusted odds ratio 2.84, 95% CI 2.11-3.83) but was not significantly associated with mortality (adjusted odds ratio 0.72, 95% CI 0.29-1.80) or readmission (adjusted odds ratio 0.88, 95% CI 0.68-1.14) when compared with low continuity of care. CONCLUSIONS: Increased weekend continuity of care is associated with reduced length of stay. Improvement in weekend cross-coverage and patient handoffs may be useful to improve clinical outcomes.

Estrogen receptor ß variants modify risk for Alzheimer's disease in a multiethnic female cohort.

BACKGROUND: Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of ESR2 polymorphisms on age at onset of AD in a multiethnic cohort of women. OBJECTIVES: To determine whether gene variants would affect risk for AD differently in women of different population ancestries. METHODS: Among 1,686 women participating in the Washington Heights Inwood Columbia Aging Project (WHICAP), association with risk for AD was assessed for 20 ESR2 single-nucleotide polymorphisms (SNPs) using multivariate logistic regression, adjusting for age at time of study enrollment, presence of an APOE ε4 allele, years of education, and body mass index. RESULTS: Increased risk for AD was associated with four ESR2 SNPs in women of predominantly Caucasian AIMS-defined ancestry: rs944045, rs1256062, rs10144225, and rs2274705 (OR range 1.6-1.9, empiric p-value range 0.002-0.004). A separate SNP (rs10137185) was associated with decreased risk for AD in women who identified themselves as Black (OR 0.6, 95% CI = 0.4-0.9). When vascular risk factors were included in the model, a separate SNP (rs1256059) was associated with increased risk for AD in women of admixed/Hispanic ancestry (OR 1.5, 95% CI = 1.1-2.4). CONCLUSIONS: ESR2 polymorphisms affect risk for AD in women, and risk alleles vary by AIMs-defined ancestry and self-identified ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid risk factors mediating SNP effect on risk for AD by group.

Electronic health record use, intensity of hospital care, and patient outcomes.

OBJECTIVE: Previous studies have suggested that weekend hospital care is inferior to weekday care and that this difference may be related to diminished care intensity. The purpose of this study was to determine whether a metric for measuring intensity of hospital care based on use of the electronic health record was associated with patient-level outcomes. METHODS: We performed a cohort study of hospitalizations at an academic medical center. Intensity of care was defined as the hourly number of provider accessions of the electronic health record, termed "electronic health record interactions." Hospitalizations were categorized on the basis of the mean difference in electronic health record interactions between the first Friday and the first Saturday of hospitalization. We used regression models to determine the association of these categories with patient outcomes after adjusting for covariates. RESULTS: Electronic health record interactions decreased from Friday to Saturday in 77% of the 9051 hospitalizations included in the study. Compared with hospitalizations with no change in Friday to Saturday electronic health record interactions, the relative lengths of stay for hospitalizations with a small, moderate, and large decrease in electronic health record interactions were 1.05 (95% confidence interval [CI], 1.00-1.10), 1.11 (95% CI, 1.05-1.17), and 1.25 (95% CI, 1.15-1.35), respectively. Although a large decrease in electronic health record interactions was associated with in-hospital mortality, these findings were not significant after risk adjustment (odds ratio 1.74, 95% CI, 0.93-3.25). CONCLUSIONS: Intensity of inpatient care, measured by electronic health record interactions, significantly diminished from Friday to Saturday, and this decrease was associated with length of stay. Hospitals should consider monitoring and correcting temporal fluctuations in care intensity.

Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome.

Background/Aims. Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). In women with Down syndrome, we examined the relation of polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age at onset and risk of AD. HSD17B1 encodes the enzyme 17ß-hydroxysteroid dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol. Methods. Two hundred and thirty-eight women with DS, nondemented at baseline, 31-78 years of age, were followed at 14-18-month intervals for 4.5 years. Women were genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in the HSD17B1 gene region, and their association with incident AD was examined. Results. Age at onset was earlier, and risk of AD was elevated from two- to threefold among women homozygous for the minor allele at 3 SNPs in intron 4 (rs676387), exon 6 (rs605059), and exon 4 in COASY (rs598126). Carriers of the haplotype TCC, based on the risk alleles for these three SNPs, had an almost twofold increased risk of developing AD (hazard ratio = 1.8, 95% CI, 1.1-3.1). Conclusion. These findings support experimental and clinical studies of the neuroprotective role of estrogen.

Estrogen receptor-Beta variants are associated with increased risk of Alzheimer's disease in women with down syndrome.

BACKGROUND/AIMS: Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). We examined the relation of polymorphisms in the gene for the estrogen receptor-beta (ESR2) to the risk of AD in women with Down syndrome. METHODS: Two hundred and forty-nine women with Down syndrome, 31-70 years of age and nondemented at baseline, were followed at 14- to 18-month intervals for 4 years. Women were genotyped for 13 single-nucleotide polymorphisms (SNPs) in the ESR2 gene, and their association with AD incidence was examined. RESULTS: Among postmenopausal women, we found a 2-fold increase in the risk of AD for women carrying 1 or 2 copies of the minor allele at 3 SNPs in introns seven (rs17766755) and six (rs4365213 and rs12435857) and 1 SNP in intron eight (rs4986938) of ESR2. CONCLUSION: These findings support a role for estrogen and its major brain receptors in modulating susceptibility to AD in women.

Replication of the LINGO1 gene association with essential tremor in a North American population.

A marker in the LINGO1 gene, rs9652490, showing significant genome-wide association with essential tremor (ET), was recently reported in an Icelandic population. To replicate this association in an independent population from North America, we genotyped 15 SNPs in the LINGO1 gene in 257 Caucasian ET cases ('definite,' 'probable' or 'possible') and 265 controls enrolled in an epidemiological study at Columbia University. We observed a marginally significant association with allele G of the marker rs9652490 (P=0.0569, odds ratio (OR)=1.33). However, for 'definite' or 'probable' ET, rs9652490 was significantly associated with ET (P=0.03, OR=1.41). Our subsequent analysis of early-onset ET (age at onset <40 years) revealed that three SNPs, rs177008, rs13313467 and rs8028808, were significantly associated with ET (P=0.028, OR=1.52; P=0.0238, OR=1.54; and P=0.0391, OR=1.55, respectively). These three SNPs represent a 2.3 kb haplotype. Finally, a meta-analysis of three published studies confirms allelic association with rs9652490 and two adjacent SNPs. Our study independently confirms that the LINGO1 gene is a risk factor for ET in a Caucasian population in North America, and further shows that those with early-onset ET are likely to be at high risk.

Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor.

We evaluated an association between essential tremor (ET) and the Parkinson's disease (PD) genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA). Clinical studies demonstrate an association between ET and PD, suggesting possible shared pathophysiologies, yet LRRK2 has rarely been studied in ET, and GBA, not at all. ET cases (n = 275, including 42 with rest tremor) and controls (n = 289) were enrolled in an epidemiological study (Columbia University). Post-mortem brain tissue samples were obtained on 24 additional ET cases, including 3 with brainstem Lewy bodies. We performed a comprehensive analysis of the LRRK2 gene by genotyping 4 LRRK2 mutations (G2019S, I2020T, R1441C and Y1699C), 2 rare LRRK2 variants (L1114L and I1122V) and 19 LRRK2 SNPs. All GBA exons were sequenced in a subset of 93 Ashkenazi Jewish (AJ) cases, 62 AJ controls and 24 ET brains. LRRK2 mutations were not found in any ET cases or ET brains and none of the LRRK2 SNPs was associated with ET. GBA mutations were found in 7.5% (7/93) of AJ ET cases and 4.8% (3/62) of AJ controls (p = 0.75). 8.3% (2/24) of ET brains carried a GBA mutation. Four different heterozygous mutations were identified, including 3 previously reported mutations (N370S, R496H, and E326K) and 1 new missense variant (R44C). As suggested by several smaller prior reports, the known mutations for the LRRK2 gene are not risk factors for ET. Furthermore, a similar frequency of GBA mutations in AJ ET cases and controls suggests that GBA is not a common cause of ET either.

Genetic contribution to brachial artery flow-mediated dilation: the Northern Manhattan Family Study.

BACKGROUND: Brachial artery flow-mediated dilation (FMD) is a non-invasive measure of endothelial function. Endothelial dysfunction has been associated with traditional vascular risk factors and increased risk of cardiovascular disease. The importance of genetic contribution to FMD and baseline brachial artery diameter has not been shown in Hispanic populations. The purpose of this study was to estimate the heritability of FMD. METHODS: Flow mediated dilation and brachial artery diameter were measured in a subset of Caribbean Hispanic families from the ongoing Northern Manhattan Family Study (NOMAFS), which studies the contribution of genetics to stroke and cardiovascular risk factors. The age- and sex-adjusted heritability of FMD was estimated using variance component methods. RESULTS: The current data include 620 subjects (97 probands and 523 relatives) from 97 families. The age and sex-adjusted heritability of brachial artery diameter was 0.57 (p<0.01). The age- and sex-adjusted heritability of FMD was 0.20 (p=0.01). After additional adjustment for systolic and diastolic blood pressure, body mass index, smoking, lipid, diabetes mellitus, medication, and baseline brachial artery diameter, the heritability of FMD was 0.17 (p=0.01). CONCLUSIONS: We found modest heritability of FMD. FMD might be a reasonable phenotype for further investigation of genetic contribution to atherosclerosis.

Probing genetic overlap among complex human phenotypes.

Geneticists and epidemiologists often observe that certain hereditary disorders cooccur in individual patients significantly more (or significantly less) frequently than expected, suggesting there is a genetic variation that predisposes its bearer to multiple disorders, or that protects against some disorders while predisposing to others. We suggest that, by using a large number of phenotypic observations about multiple disorders and an appropriate statistical model, we can infer genetic overlaps between phenotypes. Our proof-of-concept analysis of 1.5 million patient records and 161 disorders indicates that disease phenotypes form a highly connected network of strong pairwise correlations. Our modeling approach, under appropriate assumptions, allows us to estimate from these correlations the size of putative genetic overlaps. For example, we suggest that autism, bipolar disorder, and schizophrenia share significant genetic overlaps. Our disease network hypothesis can be immediately exploited in the design of genetic mapping approaches that involve joint linkage or association analyses of multiple seemingly disparate phenotypes.

Towards a reference model for representing nursing information needs.

Information needs studies in clinical settings often face the problem of integrating and analyzing data collected using different study tools. Generally, a coding taxonomy or a model is developed to capture and code the study data. Significant efforts are required to develop a model that not only captures the study data but is also closer to the clinical domain to draw meaningful real world inferences. Further, a study-specific model limits comparative evaluation of studies across different institutions. In this paper, we propose a reference model for representing nursing information needs. We use an iterative and collaborative approach in representing the concepts in the model. The model consists of 33 information (need) concepts, 29 information sources and 7 categories of nursing tasks which were used to code 228 identified information need instances.

Outcome after traumatic frontal intracerebral haemorrhage: a comparison of unilateral and bilateral haematomas.

Frontal intracerebral haemorrhage (ICH) is a common result of cranial trauma. Outcome differences between bilateral and unilateral frontal ICH are not well studied but would be valuable to predict prognosis in clinical practice. Two aims are proposed in this study: first to compare the risk of developing delayed ICH after bilateral or unilateral frontal ICH, and second to determine the variables helpful to predict outcome according to the Glasgow Outcome Scale (GOS). Between January 1993 and December 1997, 694 consecutive patients with traumatic ICH were admitted to the Chang Gung Medical Center within 24 h of the trauma. Patients with ICH in sites other than the frontal lobes were excluded. A total of 161 cases (mean age 46.3+/-20.3 years), including 57 bilateral (mean age 52.5+/-18.7 years) and 104 unilateral (mean age 42.9+/-20.5 years) traumatic frontal ICH were studied. Twenty-eight of 57 patients (49%) with bifrontal ICH versus 17 of 104 patients (16%) with unilateral frontal ICH had a further, delayed ICH. In 42 of 45 patients (93%) with delayed ICH, this occurred within 5 days of the initial trauma. Multivariate logistic regression was used to select significant predictors of outcome. We found that delayed ICH (p<0.001), age (p=0.004) and mechanism of injury (p=0.001) explained the worse outcome in patients with bifrontal ICH. The best-fitting logistic regression model included three variables: delayed ICH (p=0.011), initial GCS (p=0.023), and a sum score of clinical and radiological variables (p=0.003). Bifrontal ICH tended to occur in older patients after a fall and was associated with a higher risk of developing delayed ICH or brain stem compression compared to unilateral ICH damage. Using these three variables - delayed ICH, initial GCS, and the sum score - in a logistical regression model is useful to predict outcome in patients with traumatic frontal ICH and may aid patient management.

Impact of family history of high myopia on level and onset of myopia.

PURPOSE: To investigate the impact of a positive family history of high myopia on the level and onset of myopia and its ocular components. METHODS: A cross-sectional study was conducted. The participants (aged 17 to 45 years) were categorized into four groups: normal, mild, moderate, and high myopia. The age of first glasses for myopia was used as the onset of myopia. The impact of the family history on the level and the onset of myopia was quantified. Parental effect on corneal curvature (CC), anterior chamber depth (ACD), and axial length (AXL) was analyzed. RESULTS: The study included 185 normal subjects, 170 mild, 140 moderate, and 392 high myopes. Family history was strongly associated with the probands' status (P < 6 x 10(-12)). When there was >or=1 highly myopic parent, the odds ratios (ORs) of developing mild or moderate myopia were between 2.5 and 3.7 (95% CI: 1.1-6.5) and the ORs of having high myopia were > 5.5 (95% CI: 3.2-12.6). A strong association (P = 2 x 10(-6)) between parental myopic state and the AXL in the subjects was also found, but there was no statistical relationship for ACD or CC. There was an association between high myopia in parents and the onset of myopia in children. Siblings had a weaker association with the level of myopia and had no effect on the onset of myopia. CONCLUSIONS: This study found strong familial effects on the level and onset of myopia even after adjusting for environmental factors. The parental effect on ocular components in their offspring was primarily on AXL.

Genetic and environmental contributions to carotid intima-media thickness and obesity phenotypes in the Northern Manhattan Family Study.

BACKGROUND AND PURPOSE: Both carotid intima-media thickness (IMT) and obesity are independent determinants of stroke and cardiovascular disease. The prevalence of obesity is higher in Hispanics. The genetic basis of IMT and obesity has not been well-characterized in Caribbean Hispanics. The purpose of this study was to examine the genetic and environmental contributions to IMT and obesity in this population. METHODS: The data included 440 subjects from 77 Caribbean Hispanic families. Mean IMT and maximum IMT were measured in the internal carotid artery, common carotid artery, and carotid bifurcation. The total IMT was calculated as the mean value of IMT at all segments. Obesity phenotypes included body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and skin-fold thickness. Variance component methods were used to estimate age-adjusted and sex-adjusted heritability. Bivariate analyses were conducted to test for genetic and environmental correlations between IMT and obesity. RESULTS: Heritabilities for IMT ranged from 9% to 40%, with the highest for total maximum IMT and lowest for internal carotid artery maximum IMT. Heritabilities for BMI, waist circumference, WHR, and skin-fold thickness were 44%, 47%, 5%, and 36%, respectively. There were significant genetic, but not environmental, correlations between IMT and BMI, waist circumference, and skin-fold thickness. There were no genetic or environmental correlations between IMT and WHR. CONCLUSIONS: We found a substantial genetic contribution to IMT, BMI, waist circumference, and skin-fold thickness. Obesity and IMT may share common genetic factors. Future gene mapping studies are warranted to identify genes predisposing to IMT and obesity in this population.

Immunohistochemical and ultrastructural comparative study of external lamina structure in 31 cases of cellular, classical, and melanotic schwannomas.

Unlike most soft tissue tumors, schwannoma is characterized by the presence of distinct linear, frequently duplicated external lamina (EL). Although electron microscopy remains the gold standard for demonstrating this unique feature and distinguishing its morphologic variants from mimickers, the use of two anti-EL antibodies, laminin and type IV collagen, appears to supersede electron microscopy in terms of current practice. To determine whether immunohistochemical expression correlates with ultrastructural findings, 10 cellular schwannomas, 18 classic schwannomas, and 3 melanotic schwannomas were evaluated ultrastructurally and immunohistochemically using antibodies to type IV collagen and laminin. Immunohistochemically, a moderate to strong intensity in more than 50% of tumor cells was detected using either antibody in most cases of cellular schwannomas (70%), the Antoni A areas of classic schwannomas (78%), and melanotic schwannomas (67%). Ultrastructurally, the presence of diffusely continuous, duplicated EL was observed in 30% of cellular schwannomas and 56% of classic schwannomas, while 50% of cellular schwannomas and 22% of classic schwannomas showed either continuous simple EL or discontinuous but duplicated EL alone. In addition, two cellular schwannomas (20%) and four classic schwannomas (22.2%) had only a simple layer of EL in focal areas. In contrast to the distinct immunostaining surrounding individual cells seen in the former two subtypes, all three melanotic schwannomas displayed a biphasic-staining pattern of the EL (ie, individual cell and nested), which was confirmed at the ultrastructural level. The authors found a significant difference in intensity between the Antoni A and B areas of classic schwannomas using both laminin and type IV collagen. In addition, the intensities of laminin and type IV collagen in the Antoni A areas of classic schwannomas were significantly stronger compared with those of cellular schwannomas. Nevertheless, there was no significant difference either between two antibodies or between cellular and classic variants with regard to the extent of immunoreaction. Only in classic schwannomas did the extent of immunoreaction against both laminin and type IV collagen correlate significantly with the ultrastructural EL distribution pattern (diffusely continuous vs. discontinuous). However, this association was not detected in cases of cellular schwannomas. On the other hand, the intensities of laminin and type IV collagen did not correlate with the ultrastructural thickness of EL, irrespective of the morphologic subtypes. In conclusion, both type collagen IV and laminin are still reliable markers of EL in various types of schwannomas. Schwannomas exhibiting a monolayered EL are as strong in immunoreaction as those displaying reduplicated/thickened EL, indicating that a single layer of EL is thick enough to be identified by both antibodies with sufficient sensitivity. The peculiar biphasic EL pattern seen in melanotic schwannoma remains under-recognized, which may lead to misdiagnosis as malignant melanomas, especially in limited biopsy specimens.

Comparison of the handheld Retinomax K-Plus2 and on-table autokeratometers in children with and without cycloplegia.

PURPOSE: To compare the keratometry measurements in children by the handheld Nikon Retinomax K-Plus2 (Rmax) and the on-table Topcon KR8100 autokeratometers and evaluate the degree of agreement in the 2 instruments between children with and without cycloplegia. SETTING: Department of Ophthalmology, Kaohsiung Municipal United Hospital, and Chang-Gung Memorial Hospital, Kaohsiung, Taiwan. METHODS: The first cohort comprised 61 children who were consecutively collected in the pediatric ophthalmology clinic. The keratometry was measured under cycloplegia. The second cohort included 156 school children who received routine vision screening without cycloplegia. The horizontal and vertical keratometry data were measured by both instruments. The mean bias and agreement between the 2 types of measurements were evaluated. RESULTS: Both horizontal and vertical keratometry data from the Rmax were systemically and mildly lower than the data from the Topcon. The mean keratometric difference in the 2 types of instruments was minimal and clinically acceptable: 72% to 85% was within +/-0.5 diopter. The agreement of measured data in the children without cycloplegia was higher than that in the children with cycloplegia. CONCLUSIONS: The handheld Retinomax provided comparable data to that of the conventional on-table Topcon. It is useful in the clinic to measure keratometry in children and therefore may offer a convenient tool for assessing corneal curvature for fitting contact lenses or for implanting intraocular lenses in young children.