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PubMed1992

[A frontal cephalometric analysis].

A comprehensive frontal cephalometric analysis was developed and its normal values for Chinese adults were established in this study. This analysis includes two parts: width proportional analysis and symmetry analysis. Most linear width values of males were significantly greater than those of females as expected. However, there were no significant sex differentials in the most width ratios. Among these, the ratio Go/Z reached ca. 75%, Mx/Zy ca. 50%, L6/Go ca. 50% and the Mx/Go ca. 66.6% (2/3). Width problems and possible expansion at canine and molar areas could be evaluated through proportional analysis. To determine the locations as well as extents of dentofacial asymmetry is of great clinical value especially in orthodontic treatment. In symmetry analysis, linear differences between both side structures in vertical and horizontal directions could be calculated.

Adult↗

PubMed1996

Genomic localization of novel candidate tumor suppressor gene loci in human parathyroid adenomas.

Only one oncogene, cyclin D1/PRAD1, has an established role in parathyroid tumorigenesis, and parathyroid tumor suppressor genes on chromosome arms 1p and 11q, which still have not been identified, have also been implicated by loss of heterozygosity analysis. To investigate whether other putative tumor suppressor genes are involved in the pathogenesis of parathyroid adenomas, we performed a more comprehensive analysis of allelic losses in these tumors. Using 39 polymorphic markers, we examined each chromosome arm, excluding the short arms of the acrocentric chromosomes. In 25 parathyroid adenomas, frequent loss of heterozygosity, in > 25% of the informative cases, was observed on chromosome arms 6q (30%), 11p (27%), and 15q (35%), in addition to previously reported 1p (30%) and 11q (38%) allelic losses. To more specifically localize the smallest shared regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 6 (9 additional markers), chromosome 11 (8 additional markers), and chromosome 15 (15 additional markers). The regions most commonly deleted in these tumors were 6q22-23, 6q26-27, 11q13, 15q11-21, and 15q26-qter. All tumors with 11p loss had patterns consistent with monosomy for chromosome 11. These findings provide novel evidence for the existence of tumor suppressor genes on chromosome arms 6q and 15q that contribute commonly to the pathogenesis of parathyroid adenomas.

Adenoma↗

PubMed1994

Integrin expression by human articular chondrocytes.

OBJECTIVE: To perform a comprehensive analysis of the integrin forms expressed by normal human articular chondrocytes. METHODS: Cartilage sections and collagenase-released chondrocytes were probed with a comprehensive panel of integrin isoform-specific monoclonal antibodies (MAb), using in situ immunohistochemistry techniques, indirect immunofluorescence and flow cytometry, and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Chondrocytes in cartilage sections reacted with MAb specific for the alpha 5, alpha v, and beta 1 integrin subunits and the alpha v beta 3 and alpha v beta 5 heterodimers. They also reacted with a polyclonal antibody specific for the intracytoplasmic portion of the alpha 1 subunit. MAb specific for the alpha v subunit reacted more strongly with chondrocytes near the articular surface than with those in deeper layers of cartilage, and the alpha v beta 3-specific MAb reacted exclusively with chondrocytes within the most superficial 30 microns of cartilage. Flow cytometric analysis and SDS-PAGE analysis of immunoprecipitates prepared from extracts of cell-surface radioiodinated chondrocytes confirmed the above observations, and additionally revealed the presence of the alpha 3 beta 1 integrin. CONCLUSION: Normal human articular chondrocytes prominently display substantial quantities of the alpha 1 beta 1, alpha 5 beta 1, and alpha v beta 5 integrin heterodimers, as well as lesser quantities of the alpha 3 beta 1 and alpha v beta 3 heterodimers. The alpha v subunit-containing integrins are detected more readily on the more superficial chondrocytes than on chondrocytes deep within cartilage. These observations provide the basis for analysis of the role of chondrocyte integrins in cartilage homeostasis and in the pathogenesis of joint diseases.

Adult↗

PubMed2002

Analysis of the proteome in the human pituitary.

The pituitary is the master endocrine gland responsible for the regulation of various physiologic and metabolic processes. Proteomics offers an efficient means for a comprehensive analysis of pituitary protein expression. This paper reports on the application of proteomics for the mapping of major proteins in a normal (control) pituitary. Pituitary proteins were separated by two-dimensional gel electrophoresis with immobilized pH 3-10 gradient strips. Major protein spots that were visualized in the two-dimensional gel by silver staining were excised, and the proteins in these spots were digested with trypsin. The tryptic digests were analyzed by mass spectrometry, and the mass spectrometric data were used to identify the proteins through searches of the SWISS-PROT or NCBInr protein sequence databases. The majority of the proteins were identified on the basis of peptide mass fingerprinting data obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Several proteins were also characterized based on product-ion spectra measured by post-source decay analysis and/or liquid chromatography-electrospray-quadrupole ion trap mass spectrometry. To date, 62 prominent protein spots, corresponding to 38 different proteins, were identified. The identified proteins include important pituitary hormones, structural proteins, enzymes, and other proteins. The protein identification data were used to establish a two-dimensional reference database of the human pituitary, which can be accessed over the Internet (http://www.utmem.edu/proteomics). This database will serve as a tool for further proteomics studies of pituitary protein expression in health and disease.

Computational Biology↗

PubMed2024

Exploring Regulatory Roles of Transposable Elements in EMT and MET through Data-Driven Analysis: Insights from regulaTER.

Gene expression is regulated at the transcriptional and translational levels and a plethora of epigenetic mechanisms. Regulation of gene expression by transposable elements is well documented. However, a comprehensive analysis of their regulatory roles is challenging due to the lack of dedicated approaches to define their contribution. Here, we present regulaTER, a new R library dedicated to deciphering the regulatory potential of transposable elements in a given phenotype. regulaTER utilizes a variety of genomics data of any origin and combines gene expression level information to predict the regulatory roles of transposable elements. We further validated its capabilities using data generated from an epithelial-mesenchymal and mesenchymal-epithelial transition cellular model. regulaTER stands out as an essential asset for uncovering the impact of transposable elements on the regulation of gene expression, with high flexibility to perform a range of transposable element-focused analyses. Our results also provided insights on the contribution of the MIR and B element subfamilies in regulating EMT and MET through the FoxA transcription factor family. regulaTER is publicly available and can be downloaded from https://github.com/karakulahg/regulaTER.

DNA Transposable Elements↗

PubMed2002

Tools for comparative analysis of alternatives: competing or complementary perspectives?

A third generation of environmental policy making and risk management will increasingly impose environmental measures, which may give rise to analyzing countervailing risks. Therefore, a comprehensive analysis of all risks associated with the decision alternatives will aid decision-makers in prioritizing alternatives that effectively reduce both target and countervailing risks. Starting with the metaphor of the ripples caused by a stone that is thrown into a pond, we identify 10 types of ripples that symbolize, in our case, risks that deserve closer examination: direct, upstream, downstream, accidental risks, occupational risks, risks due to offsetting behavior, change in disposable income, macro-economic changes, depletion of natural resources, and risks to the manmade environment. Tools to analyze these risks were developed independently and recently have been applied to overlapping fields of application. This suggests that either the tools should be linked in a unified framework for comparative analysis or that the appropriate field of application for single tools should be better understood. The goals of this article are to create a better foundation for the understanding of the nature and coverage of available tools and to identify the remaining gaps. None of the tools is designed to deal with all 10 types of risk. Provided data suggest that, of the 10 types of identified risks, those associated with changes in disposable income may be particularly significant when decision alternatives differ with respect to their effects on disposable income. Finally, the present analysis was limited to analytical questions and did not capture the important role of the decision-making process itself.

Cost-Benefit Analysis↗

PubMed1999

Combined spectral karyotyping and DAPI banding analysis of chromosome abnormalities in myelodysplastic syndrome.

Spectral karyotyping (SKY) is a new molecular cytogenetic technique that allows simultaneous visualization of each chromosome in a different color. We have used SKY for comprehensive analysis of 20 myelodysplastic syndromes (MDSs) (13 primary MDSs, 3 therapy-related MDSs, and 4 acute leukemias developed from MDS, including 1 cell line established from a secondary leukemia), previously analyzed by G-banding. To locate the chromosomal breakpoints, DAPI-counterstained band images from all metaphases were transformed to G-band-like patterns. By using SKY, it was possible to identify the origin and organization of all clonal marker chromosomes (mar), as well as the origin of all abnormalities defined as additional material of unknown origin (add) or homogeneously staining regions (hsr) by G-banding. In total, SKY identified the chromosomal basis of 38 mar, add, and hsr, corrected 8 abnormalities misidentified by G-banding, and revealed 6 cryptic translocations in 5 cases. Total or partial chromosomal loss (mainly of -5/5q- and -7/7q-) is the most frequent cytogenetic abnormality in MDS. In 3 of 11 cases with -5/5q- and in 4 of 8 with -7/7q-, lost material was detected by SKY in unbalanced translocations. A total of 60 chromosomal losses were identified by G-banding in 16 cases with multiple chromosome abnormalities involving at least 3 chromosomes. For 26 of these losses (43%), SKY analysis suggested that the losses were not complete, but had been translocated to a variety of partner chromosomes. Moreover, SKY analysis revealed that a ring chromosome in a case of acute leukemia developed from MDS contained three to six segments that originated from chromosome 21 material. Fluorescence in situ hybridization showed the amplification of the AML1 gene on regions derived from chromosome 21, providing the first evidence of amplification involving this gene in MDS. Genes Chromosomes Cancer 26:336-345, 1999.

Adult↗

PubMed2000

Laparoscopic splenectomy in chronic idiopathic thrombocytopenic purpura.

Splenectomy remains the definitive treatment for idiopathic thrombocytopenic purpura (ITP). Issues related to timing of splenectomy, perioperative management of platelet count, deep vein thrombosis prophylaxis, and preoperative vaccination are not standardized. Predicting the outcome of splenectomy is desirable but, again, consistent evidence for a particular approach is lacking. Laparoscopic splenectomy, first introduced in 1991, has removed some of the barriers to acceptance of splenectomy and may well change its place in the various treatment algorithms. This article reviews current knowledge with respect to laparoscopic splenectomy and provides an analysis of current evidence regarding issues of safety, efficacy, and cost effectiveness. Surgical technique is briefly reviewed. The information is drawn from a comprehensive analysis of the literature, as well as my own large experience with laparoscopic splenectomy, the majority of which has been focused on laparoscopic splenectomy for ITP.

Chronic Disease↗

PubMed1992

Electronystagmographic features in some peripheral and central vestibular disorders: application of multiple discriminant analysis of electronystagmographic parameters.

In routine clinical electronystagmographic (ENG) tests (postrotatory, optokinetic, caloric and tracking tests), eye movement signals were analyzed and a multiple discriminant analysis was carried out with the aid of a microcomputer. Six parameters were selected and, based on these, two functions for discriminating between peripheral and central disorders were established. Discrimination between 35 patients with peripheral lesions and 15 patients with central lesions was made with a correct classification rate of 97.1 and 86.7%, respectively. These rates are significantly higher than that of any single ENG test analysis. Our results indicate that the clinical application of ENG can be improved by searching for more sensitive ENG parameters and adopting the comprehensive analysis approach.

Adult↗

PubMed2002

Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression).

The breast cancer promoting effects of estrogen and the chemopreventive effects of tamoxifen are thought to be mediated by the estrogen receptor, a ligand-dependent transcription factor. Therefore, comprehensive analysis of gene expression profiles following estrogen or tamoxifen treatment may help us better understand the role estrogen plays in tumorigenesis. We utilized SAGE (Serial Analysis of Gene Expression) technology to identify genes regulated by estrogen and tamoxifen in the ZR75-1 estrogen dependent breast cancer cell line. In this manner we have identified several genes that were regulated by estrogen or tamoxifen. Here we report the identification and initial characterization of EIT-6 (Estrogen Induced Tag-6), a novel nuclear protein and a new member of the evolutionarily conserved SM-20 family of growth regulatory immediate-early genes. EIT-6 appears to be a direct transcriptional target of the estrogen receptor and constitutive expression of EIT-6 promotes colony growth in human breast cancer cells. These data indicate that EIT-6 may play a role in estrogen induced cell growth.

Amino Acid Sequence↗

PubMed1994

Speech rate and rhythm in cerebellar dysarthria: an acoustic analysis of syllabic timing.

Auditory-perceptual studies reported inconsistent data with respect to syllabic timing in cerebellar dysarthria, i.e. both reduced and increased variability of syllable durations. The present study performed a comprehensive analysis of syllabic timing during sentence utterances in 14 subjects with a pure cerebellar syndrome (CA). First, the CA patients presented with reduced speech tempo in terms of syllable and utterance durations. Second, a tendency for intrautterance syllabic isochrony, being an aspect of the percept of 'scanning speech', characterized a subgroup of patients with cerebellar dysarthria. Third, increased interutterance durational variability was found in three out of the five syllables considered. Thus, both reduced intrautterance and increased interutterance variability of syllable durations may pertain to cerebellar dysarthria. The latter dimension, however, seems to be more prominent.

Adult↗

PubMed2026

Human Umbilical Cord Mesenchymal Stem Cells in Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) Therapy: Mechanisms, Clinical Efficacy, and Future Perspectives.

There is currently no approved drug treatment for metabolic dysfunction-related fatty liver disease (MAFLD). Umbilical cord-derived mesenchymal stem cells (UC-MSCs) show therapeutic potential, but their mechanism of action is remains incompletely understood. Different from previous reviews that focused on a single pathway, this article presents three important contributions: First, it constructs an integrated "multi-target synergy network" model, clarifying how UC-MSCs coordinate and regulate the inflammatory, metabolic and fibrotic processes through the interactions between the AMPK/mTOR, Nrf2/HO-1 and TGF-β/Smad pathways; Second, it systematically assesses recent clinical trials (2022-2025), identifying several unaddressed barriers to transformation, including the lack of histological endpoint indicators, batch-to-batch differences, and the absence of dose exploration studies; Third, we integrate the latest developments from 2024 to 2025, particularly mitochondrial transfer (mediated by tunnel nanotubes and accompanied by quantitative efficacy data) and exosome circular RNA networks [Formula: see text], which have not been covered in previous reviews. Based on the above analysis, we also propose specific suggestions for standardized GMP production, mandatory genomic stability testing, and long-term safety registration. This review provides a comprehensive analysis of elaborates on the treatment of MAFLD with UC-MSCs from a mechanistic and translational perspective, based on the extensive updates of relevant literature.

Humans↗

PubMed2001

The role of introgressive hybridization in the evolution of the Gila robusta complex (Teleostei: Cyprinidae).

The extent and impact of introgressive hybridization was examined in the Gila robusta complex of cyprinid fishes using mitochondrial DNA (mtDNA) sequence variation. Lower Colorado River basin populations of G. robusta, G. elegans, and G. cypha exhibited distinct mtDNAs, with only limited introgression of G. elegans into G. cypha. The impact of hybridization was significant in upper Colorado River basin populations; most upper basin fishes sampled exhibited only G. cypha mtDNA haplotypes, with some individuals exhibiting mtDNA from G. elegans. The complete absence of G. robusta mtDNA, even in populations of morphologically pure G. robusta, indicates extensive introgression that predates human influence. Analysis of the geographic distribution of variation identified two distinctive G. elegans lineages; however, the small number of individuals and localities sampled precluded a comprehensive analysis. Analysis of haplotype and population networks for G. cypha mtDNAs from 15 localities revealed low divergence among haplotypes; however, significant frequency differences among populations within and among drainages were found, largely attributable to samples in the Little Colorado River region. This structure was not associated with G. cypha and G. robusta, as morphotypes from the same location are more similar than conspecific forms in other locations. This indicates that morphological and mtDNA variation are affected by different evolutionary forces in Colorado River Gila and illustrates how both hybridization and local adaptation can play important roles in evolution.

Animals↗

PubMed2002

Analysis of age-dependant alteration in the brain gene expression profile following induction of hydrocephalus in rats.

Hydrocephalus is associated with gradual progressive impairment and destruction of cerebral axons and neurons. To provide a comprehensive analysis of gene expression changes in brain due to experimental hydrocephalus we used a DNA microarray screening technique. Hydrocephalus was induced in 3-week-old and 8- to 10-week-old rats by injection of kaolin into cisterna magna. Following induction of hydrocephalus, samples of frontoparietal cerebrum were studied 3 and 36 weeks later in young rats and 1.5 weeks later in adult rats. At the transcriptional level, young rats with subacute hydrocephalus showed overexpression of genes involved in synaptic transmission in parallel to genes associated with protective and compensatory mechanisms. Those with chronic hydrocephalus exhibited some similar changes among synapse-related genes but suppression of other neuronal genes. Expression of myelin-related genes was increased in both groups of rats with early onset hydrocephalus but suppressed in adult rats with acute hydrocephalus. Changes in genes related to extracellular matrix molecules suggest that there might be remodeling in this compartment. Adult rats showed elevated expression of inflammatory genes, likely related to kaolin-induced inflammation, but they failed to show changes in genes involved in compensatory or protective mechanisms. These results indicate that there is an age- and duration-dependent difference in the gene expression profiles of kaolin-induced hydrocephalus and they present avenues for future research.

Aging↗

PubMed2002

Twists, knots, and rings in proteins. Structural definition of the cyclotide framework.

In recent years an increasing number of miniproteins containing an amide-cyclized backbone have been discovered. The cyclotide family is the largest group of such proteins and is characterized by a circular protein backbone and six conserved cysteine residues linked by disulfide bonds in a tight core of the molecule. These form a cystine knot in which an embedded ring formed by two of the disulfide bonds and the connecting backbone segment is threaded by a third disulfide bond. In the current study we have undertaken high resolution structural analysis of two prototypic cyclotides, kalata B1 and cycloviolacin O1, to define the role of the conserved residues in the sequence. We provide the first comprehensive analysis of the topological features in this unique family of proteins, namely rings (a circular backbone), twists (a cis-peptide bond in the Möbius cyclotides) and knots (a knotted arrangement of the disulfide bonds).

Amino Acid Sequence↗

PubMed2001

Cytochrome cd1, reductive activation and kinetic analysis of a multifunctional respiratory enzyme.

Paracoccus pantotrophus cytochrome cd(1) is an enzyme of bacterial respiration, capable of using nitrite in vivo and also hydroxylamine and oxygen in vitro as electron acceptors. We present a comprehensive analysis of the steady state kinetic properties of the enzyme with each electron acceptor and three electron donors, pseudoazurin and cytochrome c(550), both physiological, and the non-physiological horse heart cytochrome c. At pH 5.8, optimal for nitrite reduction, the enzyme has a turnover number up to 121 s(-1) per d(1) heme, significantly higher than previously observed for any cytochrome cd(1). Pre-activation of the enzyme via reduction is necessary to establish full catalytic competence with any of the electron donor proteins. There is no significant kinetic distinction between the alternative physiological electron donors in any respect, providing support for the concept of pseudospecificity, in which proteins with substantially different tertiary structures can transfer electrons to the same acceptor. A low level hydroxylamine disproportionase activity that may be an intrinsic property of cytochromes c is also reported. Important implications for the enzymology of P. pantotrophus cytochrome cd(1) are discussed and proposals are made about the mechanism of reduction of nitrite, based on new observations placed in the context of recent rapid reaction studies.

Animals↗

PubMed1990

Analysis of lymphocytic infiltration in uveal melanoma.

Among 27 uveal melanomas, five were found to contain tumor infiltrating lymphocytes (TILs). Four had high levels of lymphocytes, and the fifth had comparatively low levels but adequate numbers for comprehensive analysis. The TILs were analyzed by flow cytometry to determine the relative proportions of lymphocyte subsets and markers of lymphocyte activation. The results show the predominance of T-suppressor/cytotoxic lymphocytes and insignificant levels of B-cells present in the infiltrate. The T-suppressor/cytotoxic cells were generally activated to a higher degree than the T-helper cells when assayed for levels of the histocompatibility antigen, HLA-DR. T-helper cells expressed more interleukin (IL-2) receptor (Tac) than T-suppressor/cytotoxic cells.

Biomarkers↗

PubMed2026

Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.

BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2 = 99.9%, p < 0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2 = 82.1%, p < 0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2 = 67.3%, p = 0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2 = 65.0%, p = 0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p = 0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).

Humans↗