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1.
Nat Commun ; 14(1): 8239, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38086824

ABSTRACT

Electrons at the border of localization generate exotic states of matter across all classes of strongly correlated electron materials and many other quantum materials with emergent functionality. Heavy electron metals are a model example, in which magnetic interactions arise from the opposing limits of localized and itinerant electrons. This remarkable duality is intimately related to the emergence of a plethora of novel quantum matter states such as unconventional superconductivity, electronic-nematic states, hidden order and most recently topological states of matter such as topological Kondo insulators and Kondo semimetals and putative chiral superconductors. The outstanding challenge is that the archetypal Kondo lattice model that captures the underlying electronic dichotomy is notoriously difficult to solve for real materials. Here we show, using the prototypical strongly-correlated antiferromagnet CeIn3, that a multi-orbital periodic Anderson model embedded with input from ab initio bandstructure calculations can be reduced to a simple Kondo-Heisenberg model, which captures the magnetic interactions quantitatively. We validate this tractable Hamiltonian via high-resolution neutron spectroscopy that reproduces accurately the magnetic soft modes in CeIn3, which are believed to mediate unconventional superconductivity. Our study paves the way for a quantitative understanding of metallic quantum states such as unconventional superconductivity.

2.
Phys Rev Lett ; 129(8): 087201, 2022 Aug 19.
Article in English | MEDLINE | ID: mdl-36053701

ABSTRACT

We report an excellent realization of the highly nonclassical incommensurate spin-density wave (SDW) state in the quantum frustrated antiferromagnetic insulator Cs_{2}CoBr_{4}. In contrast to the well-known Ising spin chain case, here the SDW is stabilized by virtue of competing planar in-chain anisotropies and frustrated interchain exchange. Adjacent to the SDW phase is a broad m=1/3 magnetization plateau that can be seen as a commensurate locking of the SDW state into the up-up-down (UUD) spin structure. This represents the first example of the long-sought SDW-UUD transition in triangular-type quantum magnets.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2015: 8107-10, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26738175

ABSTRACT

The aim of the study was to evaluate the applicability of electroencephalogram (EEG) spectral asymmetry index (SASI) for discrimination of the effect of negative and positive emotions on human brain bioelectrical activity. SASI has been previously proposed as a method to detect depression based on the balance of EEG theta and beta frequency band powers. Emotions were evoked on 22 healthy subjects using emotional pictures portraying humans from International Affective Picture System (IAPS) and late response to stimuli was examined (1700-2200 ms). Electroencephalogram (EEG) was recorded in 30 channels divided into 10 brain regions: left frontal, right frontal, left temporal, right temporal, frontal, frontocentral, central, centroparietal, parietal and occipital. Negative stimuli, compared to neutral stimuli, significantly increased SASI in frontocentral, central, centroparietal, parietal and occipital areas. Positive stimuli, compared to neutral stimuli, significantly decreased SASI in left temporal, centroparietal, parietal and occipital areas. The results indicate that SASI provides a good discrimination between the effects of negative, neutral and positive emotions on human EEG.


Subject(s)
Emotions , Brain , Brain Mapping , Depression , Electroencephalography , Humans
4.
Article in English | MEDLINE | ID: mdl-26737210

ABSTRACT

There is a high demand for objective indicators in diagnosis of depression as diagnosis of depression is still based on psychiatrist's subjective judgment. A nonlinear method Lempel Ziv Complexity (LZC) has been previously successfully used for detection of neuronal or mental disorders based on electroencephalographic (EEG) signals. However, the method overlooks the high frequency content of EEG signals. Therefore, this study is aimed to find out whether the use of Multiscale Lempel Ziv Complexity (MLZC), considering also high frequencies, could overcome the limitations of LZC and better differentiate depression. In current study the EEG recordings were carried out on the groups of depressive and healthy subjects of 11 volunteers each. The LZC and MLZC were calculated on resting EEG signals in eyes open condition from 30 channels at a length of 2 minutes. The results revealed the incapability of traditional LZC to differentiate depressive subjects from healthy controls in eyes open condition, while MLZC differentiated two groups in numerous channels at different frequencies, giving the highest classification accuracy in channel F3 (86 %) at frequencies 9 and 15.5 Hz. The results indicate that the high frequency information, which is lost in calculation of traditional LZC, has a great value in differentiating between depressive and control groups.


Subject(s)
Depression/diagnosis , Electroencephalography/methods , Signal Processing, Computer-Assisted , Adult , Case-Control Studies , Depression/physiopathology , Eye , Female , Humans , Male , Middle Aged
5.
Am J Transplant ; 10(3): 527-34, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20055803

ABSTRACT

In contrast to immune restrictions that pertain for solid organ transplants, the tolerogenic milieu of the eye permits successful corneal transplantation without systemic immunosuppression, even across a fully MHC disparate barrier. Here we show that recipient and donor expression of decay accelerating factor (DAF or CD55), a cell surface C3/C5 convertase regulator recently shown to modulate T-cell responses, is essential to sustain successful corneal engraftment. Whereas wild-type (WT) corneas transplanted into multiple minor histocompatibility antigen (mH), or HY disparate WT recipients were accepted, DAF's absence on either the donor cornea or in the recipient bed induced rapid rejection. Donor or recipient DAF deficiency led to expansion of donor-reactive IFN-gamma producing CD4(+) and CD8(+) T cells, as well as inhibited antigen-induced IL-10 and TGF-beta, together demonstrating that DAF deficiency precludes immune tolerance. In addition to demonstrating a requisite role for DAF in conferring ocular immune privilege, these results raise the possibility that augmenting DAF levels on donor corneal endothelium and/or the recipient bed could have therapeutic value for transplants that clinically are at high risk for rejection.


Subject(s)
CD55 Antigens/metabolism , Corneal Transplantation/methods , Animals , Cell Membrane/metabolism , Graft Rejection , Immune System , Immune Tolerance , Interferon-gamma/metabolism , Interleukin-10/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Minor Histocompatibility Antigens/metabolism , Models, Biological , Transforming Growth Factor beta/metabolism
6.
Gesundheitswesen ; 71(5): 265-74, 2009 May.
Article in German | MEDLINE | ID: mdl-19387929

ABSTRACT

BACKGROUND: The corrosion of drinking water pipe materials can release different elements into tap water. Especially important in this context is the heavy metal lead, which mainly leaches from the peripheral water distribution system. Lead is known to have numerous adverse effects especially to infants and children. AIM AND METHOD: The aim of this project was to assess the present state of drinking water contamination with lead in Lower Saxony and to promote the replacement of lead pipes. For this purpose a project was initiated comprising three parts. Firstly, a free examination of drinking water was offered in cooperation with local public health departments for private households with young women and families with children living in buildings constructed before 1974. Participants were asked to collect a cold tap water sample in their household after nocturnal stagnation and to complete a questionnaire. The collected samples were analysed by atomic absorption spectrometry for their lead concentration. Secondly, data from local public health departments on results of lead measurements, especially in buildings for the public, were collected and analysed. Finally, a working group 'lead replacement' consisting of representatives of all relevant parties (e.g., tenant and landlord associations, handicraft, building and health administration) was initiated. RESULTS: In the project in total 2,901 tap water samples from households were collected between the years 2005 and 2007. Of these, 7.5% had lead concentrations exceeding 10 microg/L (recommended limit of the World Health Organisation) and 3.3% had concentrations above the limit of the German drinking water ordinance (25 microg/L). There were remarkable regional differences in the frequency of tap water contamination. Multi-family houses were more frequently affected than single and double family houses. Additional data were collected in a preceding study in southern Lower Saxony. Of the 1 434 stagnation samples, 3.1% had lead concentrations greater than 10 microg/L and 0.6% had concentrations above the former limit of the German drinking water regulations of 40 microg/L.


Subject(s)
Construction Materials/analysis , Environmental Monitoring , Lead/analysis , Water Pollutants, Chemical/analysis , Water Supply/analysis , Corrosion , Germany , Materials Testing
7.
Br J Ophthalmol ; 92(8): 1108-11, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18653604

ABSTRACT

BACKGROUND/AIMS: To determine if disease severity is associated with a family history of keratoconus. METHODS: Markers of disease severity in the CLEK Study cohort were assessed to determine if they could discriminate individuals with and without family history. Logistic regression was used to examine association between corneal scarring, average corneal power, flat and steep keratometry readings, and higher-order root mean square (RMS) wavefront error with family history. RESULTS: In univariate analyses, none of the severity indices had any significant associations with family history; however, contact lens use, gender, and Caucasian race were found to be significant predictors. After controlling for these confounders, there were no significant associations between any severity indices and family history. CONCLUSIONS: Presence or absence of family history is not associated with more severe clinical disease, at least when each marker for severity is considered independently. The results of this analysis are important for genetic studies of keratoconus in that it will allow recruitment of keratoconus patients across all stages of disease severity because it does not influence familial aggregation.


Subject(s)
Eye Diseases, Hereditary/genetics , Keratoconus/genetics , Cicatrix/complications , Contact Lenses/adverse effects , Cornea/physiopathology , Corneal Topography/methods , Eye Diseases, Hereditary/etiology , Eye Diseases, Hereditary/physiopathology , Female , Follow-Up Studies , Humans , Keratoconus/etiology , Keratoconus/physiopathology , Male , Risk Factors , Severity of Illness Index , Sex Factors
8.
J Clin Pharm Ther ; 33(2): 165-73, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18315782

ABSTRACT

BACKGROUND AND OBJECTIVES: The pharmacotherapy of psychosis often differs between countries and with respect to treatment guidelines. Little is known about the treatment of first episode psychosis in countries of the former Soviet Union. The objective of the study was to analyse and describe the pharmacotherapy of first episode psychosis in Estonia. METHODS: Case notes for consecutive patients with schizophrenia, schizotypal or delusional disorders admitted to the psychiatry clinics of the North Estonia Regional Hospital (NERH) and Tartu University Hospital (TUH) between September 2005 and September 2006 were retrospectively reviewed by a trained researcher. Treatment regimens were assessed according to prescribed doses, the incidence of antipsychotic polypharmacy and prescribing of conventional vs. atypical agents. RESULTS: There were 234 patients admitted to the NERH and TUH, 142 of which were included in the final analyses (mean age 30.3 years for males, 40.4 years for females). Patients were most frequently treated with risperidone (n = 94), olanzapine (n = 43), chlorpromazine (n = 31), haloperidol (n = 21) and quetiapine (n = 24). Fourteen patients received concurrent treatment with two or more antipsychotics for three or more treatment days. Nine patients received antipsychotics in doses exceeding the maximum recommended doses in the British National Formulary. CONCLUSIONS: The pharmacotherapy of first episode psychosis in Estonia was largely consistent with Estonian and international guidelines, however, the use of conventional antipsychotics and antipsychotic polypharmacy remained common. Estonian treatment guidelines may need to be revised to reflect the best available research evidence.


Subject(s)
Antipsychotic Agents/therapeutic use , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adult , Drug Utilization/statistics & numerical data , Estonia , Female , Health Policy , Hospitals/statistics & numerical data , Humans , Internationality , Male , Practice Guidelines as Topic
9.
Tenn Med ; 99(10): 38-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17375503

ABSTRACT

This study included 50 newborns; it was conducted in the Department of Orthopedics in Azady Hospital in Duhok, Kurdistan, Iraq, from June 1998-June 2000. The patients were 26 males (52 percent) and 24 females (48 percent). The loss of movement of the affected foot was detected in the first day after delivery in 15 cases (30 percent), later within the first week in 20 cases (40 percent) and the remaining 15 cases (30 percent) from the second to the fourth week after delivery. The condition was unilateral in 46 cases (92 percent) and bilateral in four cases (eight percent). All the patients were treated conservatively by either immobilization by a back slab of the affected limb or immobilization and physical therapy. Recovery was faster when physiotherapy was implied. All the mothers were educated to avoid two traditional methods of nursing their babies. They were advised not to wrap the newborns tightly and to avoid using the traditional crib (Landek).


Subject(s)
Foot Deformities, Congenital/therapy , Foot/physiopathology , Gait Disorders, Neurologic/therapy , Immobilization , Physical Therapy Modalities , Female , Foot Deformities, Congenital/diagnosis , Gait Disorders, Neurologic/diagnosis , Humans , Infant, Newborn , Iraq , Male , Paralysis/therapy , Prospective Studies
10.
Med Biol Eng Comput ; 43(1): 142-9, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15742733

ABSTRACT

The study compared traditional spectral analysis and a new scale-invariant method, the analysis of the length distribution of low-variability periods (LDLVPs), to distinguish between electro-encephalogram (EEG) signals with and without a weak stressor, a low-level modulated microwave field. During the experiment, 23 healthy volunteers were exposed to a microwave (450 MHz) of 7 Hz frequency on-off modulation. The field power density at the scalp was 0.16 mW cm(-2). The experimental protocol consisted of ten cycles of repetitive microwave exposure. Signals from frontal EEG channels FP1 and FP2 were analysed. Smooth power spectrum and length distribution curves of low-variability periods, as well as probability distribution close to normal, confirmed that stationarity of the EEG signal during recordings was achieved. The quantitative measure of LDLVPs provided a significant detection of the effect of the stressor for the six subjects exposed to the microwave field but for none of the sham recordings. The spectral analysis revealed a significant result for one subject only. A significant effect of the exposure to the EEG signal was detected in 25% of subjects, with microwave exposure increasing EEG variability. The effect was not detectable by power spectral measures.


Subject(s)
Electroencephalography/radiation effects , Electromagnetic Fields , Adult , Brain/physiology , Brain/radiation effects , Electroencephalography/methods , Female , Humans , Male , Microwaves , Signal Processing, Computer-Assisted
11.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 4225-8, 2004.
Article in English | MEDLINE | ID: mdl-17271236

ABSTRACT

This study is focused on low-level modulated microwave field effects on human EEG theta, alpha and beta rhythms at different modulation frequencies. During the experiment 13 healthy volunteers were exposed to a microwave (450 MHz) with 7 Hz, 14 Hz and 21 Hz frequency on-off modulation. The field power density at the scalp was 0.16 mW/cm(2). The experimental protocol consisted of five cycles of the repetitive microwave stimulation at fixed modulation frequencies. Changes in the EEG rhythms energy became evident in the case of modulation frequencies higher than the EEG rhythms frequencies. The changes varied strongly from subject to subject. Microwave exposure caused statistically significant changes in the EEG theta rhythm energy and for occipital channels in the alpha rhythm energy.

12.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 2239-42, 2004.
Article in English | MEDLINE | ID: mdl-17272172

ABSTRACT

This paper gives an overview of a research, which is focused on the development of the convenient device for continuous non-invasive monitoring of arterial blood pressure. The blood pressure estimation method is based on a presumption that there is a singular relationship between the pulse wave propagation time in arterial system and blood pressure. The parameter used in this study is pulse wave transit time (PWTT). The measurement of PWTT involves the registration of two time markers, one of which is based on ECG R peak detection and another on the detection of pulse wave in peripheral arteries. The reliability of beat to beat systolic blood pressure calculation during physical exercise was the main focus for the current paper. Sixty-one subjects (healthy and hypertensive) were studied with the bicycle exercise test. As a result of current study it is shown that with the correct personal calibration it is possible to estimate the beat to beat systolic arterial blood pressure during the exercise with comparable accuracy to conventional noninvasive methods.

13.
Int J Radiat Biol ; 78(10): 937-44, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12465659

ABSTRACT

PURPOSE: The aim was to examine low-level 7 Hz-modulated 450 MHz radiation effects on human performance in visually presented neuropsychological tasks associated with attention and short-term memory. MATERIALS AND METHODS: A homogeneous group of 100 subjects (37 female, 63 male) were randomly assigned to either the exposed (10-20 min, 0.158 mW cm(-2)) or the sham-exposed group. A battery of three different tests measured attention and short-term memory. Task 1 involved alternately selecting black digits from 1 to 25 in ascending order and white digits from 24 to 1 in descending order. The time spent on the task and the number of errors were recorded and analysed. Task 2 involved viewing a picture of 12 objects during 3 s, followed by a list of 24 words. The subject was required to select words representing previously presented objects. In task 3, an array of letters in 10 rows (60 in each row) was presented, and the subject was required to identify all examples of a particular two-letter combination. RESULTS: The results of tasks 1 and 3 showed a significant increase in variances of errors (p<0.05) in the exposed versus the sham-exposed group. The results of task 2 indicated a significant decrease in errors (p<0.05) in the exposed group. CONCLUSIONS: The data provide additional evidence that acute low-level exposure to microwaves modulated at 7 Hz can affect cognitive processes such as attention and short-term memory.


Subject(s)
Attention/radiation effects , Memory, Short-Term/radiation effects , Radiation , Adult , Female , Humans , Male , Microwaves , Psychological Tests
14.
Europace ; 3(3): 221-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11467464

ABSTRACT

The aim of this study was a comparative evaluation of some commonly used pacemaker control parameter combinations and algorithms for heart rate (HR) reconstruction. The quality of heart rate reconstruction was estimated comparing the reconstructed heart rate and intrinsic heart rate on the basis of a healthy person model. The model was developed on the basis of simultaneous measurement of intrinsic HR and different control parameters, which can electrically be recorded: QT-interval, (QT), ventilation (V)- and body movement activity (ACT). Relative mean square error (RMSE) between natural and reconstructed HR was used as a measure of HR reconstruction quality. It was shown that the results of linear and polynomial approximations for HR reconstruction practically coincided inside the range of interest for pacing in clinical practice 60-120 beats.min(-1) and there was no need to implement more complex algorithms. As for single-parameter systems the QT parameter had better reconstruction accuracy compared with ACT and V. All double-parameter systems presented HR reconstruction error level of around 10% that were within the limits suitable for clinical practice. The application of more than two parameters for HR reconstruction seems to be unnecessary, as the triple-parameter models appeared not to improve remarkably the quality of HR reconstruction.


Subject(s)
Adaptation, Physiological/physiology , Algorithms , Cardiac Pacing, Artificial , Heart Rate/physiology , Adult , Exercise Test , Humans , Male , Middle Aged , Reference Values , Regression Analysis
15.
Ophthalmology ; 108(2): 264-71, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11158797

ABSTRACT

OBJECTIVE: To compare the long-term effects on corneal endothelial cell density and corneal thickness of latanoprost and the fixed combination latanoprost-timolol to timolol. DESIGN: Double-masked, randomized, prospective, multicenter clinical trial. PARTICIPANTS: Three hundred sixty-nine subjects with bilateral ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density of at least 1500 cells/mm(2), central corneal thickness of less than 0.68 mm, no corneal pathologic condition on slit-lamp examination, and intraocular pressure of less than 22 mmHg after a 3-week run-in on timolol, 0.5%, once daily were included. INTERVENTION: Subjects were randomly assigned to treatment with latanoprost 0.005% (n = 127), fixed-combination latanoprost 0.005%-timolol 0.5% (FC, n = 116), or timolol 0.5% (n = 126) one drop, once daily in the morning for 1 year. All subjects were treated in both eyes. Specular microscopy and ultrasonic pachymetry were performed before treatment, and after 6 and 12 months of treatment. MAIN OUTCOME MEASURES: Mean percent change in central endothelial cell density and central corneal thickness after 1 year of treatment. RESULTS: For both corneal endothelial cell density and corneal thickness, the mean percent changes from baseline were similar in all three treatment groups. Mean percent endothelial cell change at 1 year from baseline for latanoprost, FC, and timolol was 0.3 +/- 2.2%, 0.1 +/- 1.8%, 0.0 +/- 2.5% (mean +/- standard deviation; 95% confidence interval: latanoprost vs timolol -0.2-1.0; FC vs timolol -0.4-0.7) and mean percent change in corneal thickness was -1.1 +/- 2.5%, -1.0 +/- 2.0%, 0.2 +/- 3.1%, respectively. CONCLUSIONS: Latanoprost and FC are equivalent to timolol regarding long-term corneal effects after 1 year of treatment.


Subject(s)
Antihypertensive Agents/therapeutic use , Endothelium, Corneal/drug effects , Glaucoma, Open-Angle/drug therapy , Prostaglandins F, Synthetic/therapeutic use , Timolol/therapeutic use , Adult , Aged , Aged, 80 and over , Antihypertensive Agents/administration & dosage , Cell Count , Double-Blind Method , Drug Therapy, Combination , Endothelium, Corneal/cytology , Female , Humans , Intraocular Pressure/drug effects , Latanoprost , Male , Middle Aged , Ocular Hypertension/drug therapy , Prospective Studies , Prostaglandins F, Synthetic/administration & dosage , Timolol/administration & dosage
16.
Invest Ophthalmol Vis Sci ; 41(12): 3856-61, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11053286

ABSTRACT

PURPOSE: A murine model of helminth-induced keratitis (river blindness) that is characterized by a biphasic recruitment of neutrophils (days 1-3) and eosinophils (days 3+) to the cornea has been developed. The purpose of this study was to determine the relative contribution of P- and E-selectin in recruitment of these inflammatory cells from limbal vessels to the corneal stroma. METHODS: P- and E-selectin gene knockout (-/-) mice were immunized with antigens extracted from the parasitic helminth Onchocerca volvulus. One week after the last immunization, parasite antigens were injected directly into the corneal stroma. Mice were killed on days 1 and 3 postchallenge, and eyes were immunostained with either anti-eosinophil major basic protein (MBP) or with anti-neutrophil Ab. The number of cells in the cornea was determined by direct counting. RESULTS: Recruitment of eosinophils to the cornea was significantly impaired in P-selectin(-/-) mice (63.9% fewer eosinophils on day 1 [P: = 0.0015], and 61% fewer on day 3 [P: < 0.0001]) compared with control C57BL/6 mice. In contrast, P-selectin deficiency had no effect on neutrophil recruitment to the cornea. There was no inhibition of eosinophil and neutrophil migration to the corneas of E-selectin(-/-) mice, indicating that there is no direct role for this adhesion molecule in helminth-induced keratitis. CONCLUSIONS: The present study demonstrates that P-selectin is an important mediator of eosinophil recruitment to the cornea. P-selectin interactions may therefore be potential targets for immunotherapy in eosinophil-mediated ocular inflammation.


Subject(s)
Chemotaxis, Leukocyte/immunology , Cornea/immunology , Eosinophils/immunology , Keratitis/immunology , Onchocerca volvulus/immunology , Onchocerciasis, Ocular/immunology , P-Selectin/physiology , Ribonucleases , Animals , Antigens, Helminth/immunology , Blood Proteins/immunology , Cornea/parasitology , Cornea/pathology , Disease Models, Animal , E-Selectin/genetics , E-Selectin/physiology , Enzyme-Linked Immunosorbent Assay , Eosinophil Granule Proteins , Fluorescent Antibody Technique, Indirect , Immunization , Immunoenzyme Techniques , Immunoglobulin E/analysis , Interleukin-5/metabolism , Keratitis/parasitology , Keratitis/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/immunology , Onchocerciasis, Ocular/parasitology , Onchocerciasis, Ocular/pathology , P-Selectin/genetics , Spleen/cytology , Spleen/metabolism
17.
Invest Ophthalmol Vis Sci ; 41(11): 3365-73, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11006226

ABSTRACT

PURPOSE: Gene targeted lumican-null mutants (lum(tm1sc)/lum(tm1sc)) have cloudy corneas with abnormally thick collagen fibrils. The purpose of the present study was to analyze the loss of transparency quantitatively and to define the associated corneal collagen fibril and stromal defects. METHODS: Backscattering of light, a function of corneal haze and opacification, was determined regionally using in vivo confocal microscopy in lumican-deficient and wild-type control mice. Fibril organization and structure were analyzed using transmission electron microscopy. Biochemical approaches were used to quantify glycosaminoglycan contents. Lumican distribution in the cornea was elucidated immunohistochemically. RESULTS; Compared with control stromas, lumican-deficient stromas displayed a threefold increase in backscattered light with maximal increase confined to the posterior stroma. Confocal microscopy through-focusing (CMTF) measurement profiles also indicated a 40% reduction in stromal thickness in the lumican-null mice. Transmission electron microscopy indicated significant collagen fibril abnormalities in the posterior stroma, with the anterior stroma remaining relatively unremarkable. The lumican-deficient posterior stroma displayed a pronounced increase in fibril diameter, large fibril aggregates, altered fibril packing, and poor lamellar organization. Immunostaining of wild-type corneas demonstrated high concentrations of lumican in the posterior stroma. Biochemical assessment of keratan sulfate (KS) content of whole eyes revealed a 25% reduction in KS content in the lumican-deficient mice. CONCLUSIONS: The structural defects and maximum backscattering of light clearly localized to the posterior stroma of lumican-deficient mice. In normal mice, an enrichment of lumican was observed in the posterior stroma compared with that in the anterior stroma. Taken together, these observations indicate a key role for lumican in the posterior stroma in maintaining normal fibril architecture, most likely by regulating fibril assembly and maintaining optimal KS content required for transparency.


Subject(s)
Chondroitin Sulfate Proteoglycans/deficiency , Collagen/ultrastructure , Corneal Opacity/pathology , Corneal Stroma/ultrastructure , Keratan Sulfate/deficiency , Animals , Chondroitin Sulfate Proteoglycans/metabolism , Collagen/metabolism , Corneal Opacity/metabolism , Corneal Stroma/metabolism , Gene Targeting , Keratan Sulfate/metabolism , Lumican , Mice , Mice, Knockout , Microscopy, Confocal , Microscopy, Fluorescence
18.
J Immunol ; 163(9): 4970-5, 1999 Nov 01.
Article in English | MEDLINE | ID: mdl-10528201

ABSTRACT

Invasion of the corneal stroma by neutrophils and eosinophils and subsequent degranulation disrupts corneal clarity and can result in permanent loss of vision. In the current study, we used a model of helminth-induced inflammation to demonstrate a novel role for Ab in mediating recruitment of these inflammatory cells to the central cornea. C57BL/6 and B cell-deficient (microMT) mice were immunized s. c. and injected intrastromally with Ags from the parasitic helminth Onchocerca volvulus (which causes river blindness). C57BL/6 mice developed pronounced corneal opacification, which was associated with an Ag-specific IL-5 response and peripheral eosinophilia, temporal recruitment of neutrophils and eosinophils from the limbal vessels to the peripheral cornea and subsequent migration to the central cornea. In contrast, the corneas of microMT mice failed to develop keratitis after intrastromal injection of parasite Ags unless Ags were injected with immune sera. Eosinophils were recruited from the limbal vessels to the peripheral cornea in microMT mice, but failed to migrate to the central cornea, whereas neutrophil recruitment was impaired at both stages. With the exception of IL-5, T cell responses and peripheral eosinophils were not significantly different between C57BL/6 and microMT mice. Taken together, these findings not only demonstrate that Ab is required for the development of keratitis, but also show that recruitment of neutrophils to the cornea is Ab-dependent, whereas eosinophil migration is only partially dependent upon Ab interactions.


Subject(s)
Antibodies, Helminth/physiology , B-Lymphocytes/pathology , Cornea/immunology , Eosinophils/immunology , Keratitis/immunology , Lymphopenia/genetics , Neutrophil Infiltration/immunology , Onchocerciasis, Ocular/immunology , Th2 Cells/immunology , Animals , Antibodies, Helminth/biosynthesis , Antigens, Helminth/administration & dosage , Antigens, Helminth/immunology , Chemotaxis, Leukocyte/genetics , Chemotaxis, Leukocyte/immunology , Cornea/pathology , Eosinophilia/immunology , Eosinophils/pathology , Immune Sera/physiology , Immunoglobulin G/biosynthesis , Immunoglobulin Heavy Chains/genetics , Immunoglobulin mu-Chains/genetics , Injections , Keratitis/genetics , Keratitis/pathology , Lymphopenia/immunology , Lymphopenia/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neutrophil Infiltration/genetics , Onchocerca volvulus/immunology , Onchocerciasis, Ocular/genetics , Onchocerciasis, Ocular/pathology , Stromal Cells/immunology , Th2 Cells/metabolism
19.
Hum Mol Genet ; 8(4): 625-37, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10072431

ABSTRACT

Congenital hydrocephalus is an etiologically diverse, poorly understood, but relatively common birth defect. Most human cases are sporadic with familial forms showing considerable phenotypic and etiologic heterogeneity. We have studied the autosomal recessive mouse mutation congenital hydrocephalus ( ch ) to identify candidate human hydrocephalus genes and their modifiers. ch mice have a congenital, lethal hydrocephalus in association with multiple developmental defects, notably skeletal defects, in tissues derived from the cephalic neural crest. We utilized positional cloning methods to map ch in the vicinity of D13Mit294 and confirm that the ch phenotype is caused by homozygosity for a nonsense mutation in a gene encoding a winged helix/forkhead transcription factor ( Mf1 ). Based on linked genetic markers, we performed detailed phenotypic characterization of mutant homozygotes and heterozygotes to demonstrate the pleiotropic effects of the mutant gene. Surprisingly, ch heterozygotes have the glaucoma-related distinct phenotype of multiple anterior segment defects resembling Axenfeld-Rieger anomaly. We also localized a second member of this gene family ( Hfh1 ), a candidate for other developmental defects, approximately 470 kb proximal to Mf1.


Subject(s)
Bone and Bones/abnormalities , Eye Abnormalities/genetics , Hydrocephalus/genetics , Transcription Factors/genetics , Animals , Animals, Newborn , Bone Development/genetics , Chromosome Mapping , Contig Mapping , Crosses, Genetic , DNA-Binding Proteins/genetics , Eye Abnormalities/pathology , Female , Forkhead Transcription Factors , Gene Expression Regulation, Developmental , Genetic Linkage , Genetic Markers , Heterozygote , Homozygote , Hydrocephalus/pathology , Male , Mice , Mice, Inbred Strains , Mutation , Phenotype , Trans-Activators/genetics
20.
Cornea ; 18(1): 67-72, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9894940

ABSTRACT

PURPOSE: Compare corneal endothelial image analysis by Konan SP8000 and Bio-Optics Bambi image-analysis systems. METHODS: Corneal endothelial images from 98 individuals (191 eyes), ranging in age from 4 to 87 years, with a normal slit-lamp examination and no history of ocular trauma, intraocular surgery, or intraocular inflammation were obtained by the Konan SP8000 noncontact specular microscope. One observer analyzed these images by using the Konan system and a second observer by using the Bio-Optics Bambi system. Three methods of analyses were used: a fixed-frame method to obtain cell density (for both Konan and Bio-Optics Bambi) and a "dot" (Konan) or "corners" (Bio-Optics Bambi) method to determine morphometric parameters. RESULTS: The cell density determined by the Konan fixed-frame method was significantly higher (157 cells/mm2) than the Bio-Optics Bambi fixed-frame method determination (p<0.0001). However, the difference in cell density, although still statistically significant, was smaller and reversed comparing the Konan fixed-frame method with both Konan dot and Bio-Optics Bambi comers method (-74 cells/mm2, p<0.0001; -55 cells/mm2, p<0.0001, respectively). Small but statistically significant morphometric analyses differences between Konan and Bio-Optics Bambi were seen: cell density, +19 cells/mm2 (p = 0.03); cell area, -3.0 microm2 (p = 0.008); and coefficient of variation, +1.0 (p = 0.003). There was no statistically significant difference between these two methods in the percentage of six-sided cells detected (p = 0.55). CONCLUSION: Cell densities measured by the Konan fixed-frame method were comparable with Konan and Bio-Optics Bambi's morphometric analysis, but not with the Bio-Optics Bambi fixed-frame method. The two morphometric analyses were comparable with minimal or no differences for the parameters that were studied. The Konan SP8000 endothelial image-analysis system may be useful for large-scale clinical trials determining cell loss; its noncontact system has many clinical benefits (including patient comfort, safety, ease of use, and short procedure time) and provides reliable cell-density calculations.


Subject(s)
Corneal Topography/instrumentation , Endothelium, Corneal/cytology , Adolescent , Adult , Aged , Aged, 80 and over , Cell Count , Child , Child, Preschool , Humans , Middle Aged , Observer Variation , Reference Values , Reproducibility of Results
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