bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperhomocysteinemia: A Risk Factor for Retinal Vein Occlusion
Authors: Yildirim Cem , Yaylalı Volkan , Tatlıpınar Sinan , Kaptanoğlu Bünyamin , Akpınar Soner
Published: March 2004

Purpose: The aim of the study was to investigate the plasma homocysteine levels in patients with retinal vein occlusion (RVO) in order to reveal whether hyperhomocysteinemia was a risk factor for RVO. Methods: Thirty-three consecutive patients diagnosed to have RVO of any type and 25 age- and sex-matched controls without RVO were included in this prospective case-control study. Data regarding age, sex, history of hypertension, diabetes mellitus, other vascular events, glaucoma, medications and smoking habits were obtained from all subjects. Several laboratory tests relating to vascular disease including cholesterol, triglyceride and hematocrit were checked. The plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography (normal range: 5–15 µmol/l). Plasma folate, vitamin B12 and creatinine levels were also studied since these vitamins and impairment of renal function might affect plasma tHcy values. Results: Patients with RVO had a significantly higher tHcy level (median: 11.7 µmol/l, range: 7.2–25 µmol/l) compared to controls (median: 10.3 µmol/l, range: 6.7–13.4 µmol/l; p = 0.005). Nine of 33 patients with RVO (27.3%) had an elevated plasma tHcy level, whereas none of the controls had an abnormal tHcy value (p = 0.004). Plasma folate, vitamin B12 and creatinine levels were comparable between the two groups (p > 0.05). Conclusions: The present study suggests an association between hyperhomocysteinemia and RVO. Further controlled studies with a large number of cases are needed to investigate the exact role of hyperhomocysteinemia in RVO.
Seventeen Cases of Central Serous Chorioretinopathy Associated with Systemic Corticosteroid Therapy
Authors: Koyama Makoto , Mizota Atsushi , Igarashi Yoshinori , Adachi-Usami Emiko
Published: March 2004

Purpose: To determine the relationship between the clinical characteristics of patients with central serous chorioretinopathy (CSC) and systemic corticosteroid therapy. Methods: The medical records of 17 cases of CSC that developed during systemic corticosteroid treatment from 1987 to 1999 at Chiba University Hospital were reviewed. The relationship of CSC to the age, gender, laterality, and disease requiring the corticosteroid treatment, and the dose and duration of corticosteroid therapy were examined. Results: There were 6 men and 11 women, and 2 of these developed bilateral and 15 developed unilateral CSC. The duration from the beginning of corticosteroid treatment to the onset of CSC ranged from 3 days to 23 years; 9 patients developed CSC within 1 year after the beginning of the corticosteroid medication and 6 patients after more than 8 years. The amount of corticosteroid medication at the onset of CSC ranged from 5 to 1,000 mg/day equivalent prednisolone units. There was a significant correlation between age at the onset of CSC and the daily dosage of corticosteroid. Conclusion: Even small amounts of daily corticosteroids (5–10 mg/day) can cause CSC, especially in elderly patients. These findings indicate that we need to monitor patients undergoing corticosteroid treatment carefully.
The Effects of Menopause and Hormone Replacement Therapy on Quality and Quantity of Tear, Intraocular Pressure and Ocular Blood Flow
Authors: Altintaş Özgül , Caglar Yusuf , Yüksel Nurşen , Demirci Ali , Karabaş Levent
Published: March 2004

Objective: To evaluate the effects of menopause and hormone replacement therapy (HRT) on the quality and amount of tear, intraocular pressure (IOP) and retrobulbar blood flow velocities. Patients and Methods: Twenty women aged between 40 and 50 years, free of ocular and systemic diseases and planning to receive HRT were recruited as the study group. Twenty-four healthy, age-matched but still menstruating women were enrolled as controls. On the first day of study basal and reflex Schirmer test, tear break-up time and IOP measurements (at 08.00, 12.00 and 16.00 h) were performed for all groups. On the second day of the study, the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistivity index (RI) of the ophthalmic (OA), central retinal (CRA), nasal (NSPCA) and temporal short posterior ciliary (TSPCA) arteries were determined by color Doppler imaging. The menopausal group received HRT for 2 months, when all measurements were repeated for the 15 women who had received HRT on a daily basis. Results: The quality and amount of tear decreased (p < 0.01), IOP (p < 0.01) and RI of the CRA, TPCA and NPCA (p < 0.05) increased in postmenopausal women compared with the control group. After 2 months of HRT, the quality and amount of tear had increased (p < 0.001) and the IOP had decreased (p < 0.001). The PSV of the CRA and TSPCA had decreased (p < 0.05), as had the RI in the CRA (p < 0.001), NSPCA and TSPCA (p < 0.05). Conclusion: We conclude that age-induced changes on quality and amount of tear, IOP and retrobulbar blood flow are intensified by the menopause and that it may be possible to decrease the menopausal effects on these parameters by HRT.
Measurement of pH, Electrolytes and Electrophoretic Studies of Tear Proteins in Tears of Patients with Dacryoliths: A Novel Concept for Dacryoliths
Authors: Lew Helen , Lee Sang-Yeul , Yun Yong-Soo
Published: March 2004

Dacryolithiasis is one of the causes of acquired nasolacrimal duct obstruction, although its origin is unclear. The purpose of this study was to investigate the differences in tear constituents between patients with nasolacrimal duct obstruction with dacryoliths and those without dacryoliths. In a prospective case-control study, undiluted tears were collected from 30 eyes from 30 patients with partial acquired nasolacrimal duct obstruction (PANDO) consisting of 17 PANDO patients with dacryoliths and 13 PANDO patients without dacryoliths. The pH, and the Na+, K+, Cl–, total calcium and total protein concentrations were determined. The composition of the tear proteins was assessed by cellulose acetate electrophoresis. In the tear samples from 17 eyes with PANDO/dacryoliths, the mean ± SD K+ level was 15.6 ± 3.1 mEq/l. In the tear samples from 13 PANDO controls, the mean ± SD K+ level was 19.8 ± 4.9 mEq/l. The difference between the two groups was statistically significant (p = 0.02). In the tear samples from PANDO/dacryolith patients, the mean ± SD total protein level was 129.0 ± 72.9 mg/dl. In the tear samples from the PANDO controls the mean ± SD total protein level was 261.6 ± 132.5 mg/dl. The difference between the two groups was statistically significant (p = 0.00). In the tear protein fractions from electrophoresis, a low level of lysozyme was observed in the PANDO/dacryolith samples compared with the PANDO control samples (p = 0.03). The tears from patients with PANDO due to dacryoliths showed a change in the concentrations of electrolytes and protein, particularly lysozyme, compared with that of the patients with PANDO without dacryoliths, which may be related to the pathogenesis of dacryoliths.
Bilateral Tonic Pupils with Evidence of Anti-Hu Antibodies as a Paraneoplastic Manifestation of Small Cell Lung Cancer
Authors: Wabbels Bettina K. , Elflein Heike , Lorenz Birgit , Kolling Gerold
Published: March 2004

Introduction: Ophthalmological manifestations of systemic malignancies can be either direct, metastatic or paraneoplastic. The latter are remote effects of carcinoma, often caused by autoantibodies. Ophthalmological manifestations include cancer-associated retinopathy, melanoma-associated retinopathy, opsoclonus-myoclonus syndrome or motility disorders due to effects on the neurological system. A unilateral tonic pupil is usually a benign finding but has also been described in the context of paraneoplastic syndromes, in some cases associated with anti-Hu antibodies. Case Reports: The authors describe 2 patients with bilateral symptomatic tonic pupils due to a paraneoplastic syndrome. Both patients had been treated for small cell lung cancer and had evidence of anti-Hu antibodies (autoantibodies against nuclei of neural cells) in serum and cerebrospinal fluid. Both had typical pupillary findings and hypersensitivity to diluted pilocarpine. The first patient also had sensory neuronopathy, the second affection of several cranial nerves. Discussion: To the best of our knowledge, to date no case of bilateral tonic pupils has been published due to a paraneoplastic disorder with evidence of autoantibodies. This is surprising, as it is probable that autoantibodies in paraneoplastic disorders affect both ciliary ganglions in a similar way.
The application of region-specific probes for the resolution of duplication 8p: a case report and a review of the literature
Authors: Pabst B. , Arslan-Kirchner M. , Schmidtke J. , Miller K.
Published: March 2004

The structural rearrangement in the short arm of a chromosome 8 in a clinically affected patient has been reinvestigated by FISH using whole chromosome painting and region specific YAC probes. An inverted duplication of the segment p22→p11.2 and a deletion of the subtelomeric region were demonstrated. By this approach, a more detailed resolution of the duplication/deletion 8p was possible. With the application of molecular cytogenetic methods the existence of different duplication segments within the clinical entity of duplication/deficiency 8p can be shown.
A complex chromosomal rearrangement with a translocation 4;10;14 in a fertile male carrier: ascertainment through an offspring with partial trisomy 14q24→1q22 and partial monosomy 4q27→q28
Authors: Grasshoff U. , Singer S. , Liehr T. , Starke H. , Fode B. , Schöning M. , Dufke A.
Published: March 2004

Complex chromosomal rearrangements (CCRs) are usually associated with infertility or subfertility in male carriers. If fertility is maintained, there is a high risk of abnormal pregnancy outcome. Few male carriers have been identified by children presenting with mental retardation/congenital malformations (MR/CM) or by spontaneous abortions of the spouses. We report a de novo CCR with five breakpoints involving chromosomes 4, 10 and 14 in a male carrier who was ascertained through a son presenting with MR/CM due to an unbalanced karyotype with partial trisomy 14 and partial monosomy 4. The child has a healthy elder brother. In the family history no abortions were reported. No fertility treatment was necessary. Cytogenetic analysis from the affected son showed a reciprocal translocation t(4;10) with additional chromosomal material inserted between the translocation junctions in the derivative chromosome 10. The father showed the same derivative chromosome 10 but had additionally one aberrant chromosome 14. Further molecular cytogenetic analyses determined the inserted material in the aberrant chromosome 10 as derived from chromosome 14 and revealed a small translocation with material of chromosome 4 inserted into the derivative chromosome 14. Thus the phenotype of the son is supposed to be associated with a partial duplication 14q13→q24.1 and a partial monosomy 4q27→q28. Including our case we are aware of eleven CCR cases with fertile male carriers. In eight of these families normal offspring have been reported. We propose that exceptional CCRs in fertile male carriers might form comparatively simple pachytene configurations increasing the chance of healthy offspring.
CABAND: Classification of aberrations in multicolor banded chromosomes
Authors: Horstmann M. , Obe G.
Published: March 2004

A system is presented to describe aberrations in chromosomes painted with the mBAND methodology. The CABAND (classification of aberrations in multicolor banded chromosomes) system is based on the fact that only banded parts of aberrations and not DAPI stained parts can be described accurately.
Multitude multicolor chromosome banding (mMCB) – a comprehensive one-step multicolor FISH banding method
Authors: Weise A. , Heller A. , Starke H. , Mrasek K. , Kuechler A. , Pool-Zobel B.L. , Claussen U. , Liehr T.
Published: March 2004

Multicolor chromosome banding (MCB) using one single chromosome-specific MCB probe set per experiment was previously reported as powerful tool in molecular cytogenetics for the characterization of all kinds of human marker chromosomes. However, a quick analysis of karyotypes with highly complex chromosomal changes was hampered by the problem that up to 24 MCB experiments were necessary for a comprehensive karyotype description. To overcome that limitation the 138 available region-specific microdissection-derived libraries for all human chromosomes were combined to one single probe set, called multitude MCB (mMCB). A typical fluorescence banding pattern along the human karyotype is produced, which can be evaluated either by transforming these profiles into chromosome region-specific pseudo-colors or more reliably by studying the fluorescence profiles. The mMCB probe set has been applied on chromosomes of normal male and female probands, two primary myelodysplastic syndromes and two solid tumor cell lines. Additionally, a cell line of Gorilla gorilla (GGO) studied previously by single chromosome-specific MCB was reevaluated by the mMCB method. All results were in concordance with those obtained in parallel or by other cytogenetic and molecular cytogenetic approaches indicating that mMCB is a powerful multicolor FISH banding tool for fast characterization of complex karyotypes.
Multi-locus (ML)-FISH is a reliable tool for nondisjunction studies in human oocytes
Authors: Eckel H. , Kleinstein J. , Wieacker P. , Stumm M.
Published: March 2004

In the present study, we developed a fluorescence in situ hybridization (FISH) strategy, which allows a reliable determination of the chromatid number of specific chromosomes in mature human oocytes. 168 unfertilized oocytes were analyzed by dual-color FISH with two direct-labeled locus-specific DNA probes for chromosome 13 and 21. To exclude FISH failures, metaphases with abnormal signal patterns were reanalyzed by multi-locus-FISH (ML-FISH) for chromosome 13 and 21. Following dual-color FISH, abnormal signal patterns were detected in 21 out of 108 metaphases (19.4%). 17 of these metaphases were reanalyzed by ML-FISH. In contrast to the first FISH, seven metaphases showed normal signal patterns after rehybridization, whereas ten metaphases remained abnormal. Out of these real aneuploid metaphases, five showed gain or loss of a single signal (= chromatid), two showed missing double signals (= chromosome) and three showed both. In conclusion, locus-specific FISH probes facilitate differentiation between first meiotic nondisjunction of whole chromosomes and prematurely divided chromatids. Moreover, simultaneous hybridization with a second locus-specific probe on the same chromatid (ML-FISH) helps to differentiate between FISH failures and real meiotic division errors and therefore, allows a more reliable analysis of aneuploidies in human oocytes.
Chromosome aberration dosimetry in cosmonauts after single or multiple space flights
Authors: Durante M. , Snigiryova G. , Akaeva E. , Bogomazova A. , Druzhinin S. , Fedorenko B. , Greco O. , Novitskaya N. , Rubanovich A. , Shevchenko V. , von Recklinghausen U. , Obe G.
Published: March 2004

Background and aims: Cosmic radiation is one of the main hazards for manned space exploration. Uncertainty in radiation risk estimates for crews of long-term missions are very high, and direct biological measurements are necessary. We measured chromosomal aberrations in peripheral blood lymphocytes from 33 cosmonauts involved in space missions during the past 11 years. Methods: Blood lymphocytes from the cosmonauts were stimulated to grow in vitro and were harvested at their first mitosis. Slides were either stained with Giemsa stain for dicentrics analysis, or painted with whole-chromosome DNA probes for translocation analysis (FISH). Results: A statistically significant increase in the yield of chromosomal aberrations was measured following long-term space missions in lymphocytes from cosmonauts at their first flight. No significant changes in aberration frequencies were observed for short-term taxi flights. The increase in long-term missions was consistent with the values calculated from physical dosimetry data. However, for cosmonauts involved in two or more space flights, the yield of interchromosomal exchanges was not related to the total duration of space sojourn or integral absorbed dose. Indeed, the yield of aberrations at the end of the last mission was generally in the range of background frequencies measured before the first mission. Conclusions: Chromosome aberration dosimetry can detect radiation damage during space flight, and biological measurements support the current risk estimates for space radiation exposure. However, for cosmonauts involved in multiple space missions the frequency of chromosomal aberrations is lower than expected, suggesting that the effects of repeated space flights on this particular endpoint are not simply additive. Changes in the immune system in microgravity and/or adaptive response to space radiation may explain the apparent increase in radioresistance after multiple space flights.
Screening Fanconi anemia lymphoid cell lines of non-A, C, D2, E, F, G subtypes for defects in BRCA2/FANCD1
Authors: Popp H. , Kalb R. , Fischer A. , Lobitz S. , Kokemohr I. , Hanenberg H. , Schindler D.
Published: March 2004

Biallelic mutations in BRCA2/FANCD1 were recently recognized as a rare cause of Fanconi anemia (FA). Using immunodetection with an antiserum directed against the carboxyterminus of the BRCA2 protein, we screened 38 lymphoid cell lines from FA patients whom we could not previously assign, via retroviral complementation analysis, to any of six known FA complementation groups (FA-A, -C, -D2, -E, -F, or -G). Three of these 38 cell lines lacked the 380-kDa BRCA2 signal on immunoblots. DNA sequencing showed biallelic compound and truncating mutations in two of the immuno-negative cell lines, whereas a monoallelic frameshift mutation and an amino acid substitution were detected in the third cell line. Our data show that less than 10% of unassigned FA cell lines harbor truncating mutations in BRCA2/FANCD1. This finding strongly suggests the existence of (an) additional, as yet unknown FA gene(s).
A physical map of the chromosome 12 centromere
Authors: Vermeesch J.R. , Duhamel H. , Raeymaekers P. , van Zand K. , Verhasselt P. , Fryns J.P. , Marynen P.
Published: March 2004

While current sequencing efforts consider the detection of alpha satellite repeats as logical end points for map construction, detailed maps of most pericentromeric regions are lacking to confirm this hypothesis. Here we identify the different alpha satellite families present at the pericentromeric region of chromosome 12. The order, size and location of these repeats is established using radiation hybrid analysis, pulsed field gel analysis and FISH and the maps are integrated with current sequence information. For the different classes of alpha satellites present at the chromosome 12 centromere the paralogs in the human genome were mapped by FISH. Unique sequences flanking the alpha satellite repeats were identified, some of which are not represented in the current draft sequence. This mapping effort localises the different alpha satellite repeats within the pericentromeric region and anchors them in the current maps. The novel sequences identified may serve as the end point for the ongoing sequencing efforts.
Evolution of rRNA gene clusters and telomeric repeats during explosive genome repatterning in Taterillus X (Rodentia, Gerbillinae)
Authors: Dobigny G. , Ozouf-Costaz C. , Bonillo C. , Volobouev V.
Published: March 2004

A survey of 28S and 5S rRNA gene clusters, and telomeric repeats was performed using single and double FISH in the Taterillus genus (Rodentia, Muridae, Gerbillinae). Taterillus was previously demonstrated to have undergone a very recent and extensive chromosomal evolution. Our FISH results demonstrate that rRNA genes can vary in location and number irrespective of the phylogenetic relationships. Telomeric repeats were detected in pericentromeric and interstitial regions of several chromosomes, thus providing nonambiguous evolutionary footprints of Robertsonian and tandem translocation events. These footprints are discussed in reference to the molecular process of these karyotypical changes. Also, examples of colocation of rDNA clusters and telomeric repeats lend support to their possible involvement in nucleolus formation. Finally, the presence of rRNA genes, and the extensive amplification of telomeric repeats at specific loci within a double X-autosome translocated element which were not observed on the homologous Y1 and Y2, served as basis for an epigenomic hypothesis on X-autosome translocation viability in mammals.
Chromosomal studies on sphaerodactyl lizards of genera Gonatodes and Coleodactylus (Squamata, Gekkonidae) using differential staining and fragile sites analyses
Authors: dos Santos R.M.L. , Bertolotto C.E.V. , Pellegrino K.C.M. , Rodrigues M.T. , Yonenaga-Yassuda Y.
Published: March 2004

The karyotypes of three species of sphaerodactyl gekkonid lizards are described after conventional and differential staining. Karyotypes of Gonatodeshumeralis and G. hasemani are formed by a gradual series of 32 acrocentric chromosomes, similar to those already published for other species of the genus. G. humeralis shows multiple Ag-NORs with intra-individual variability, and positive C-bands located at centromeric and telomeric regions of several chromosome pairs. Coleodactylus amazonicus, the first non-Gonatodes sphaerodactyl studied so far karyologically, exhibits 36 acrocentric/subtelocentric chromosomes and a single pair of Ag- NORs. Fragile sites were detected on two medium-sized chromosome pairs in the karyotype of G. humeralis, most of them obtained in BrdU-treated culture preparations. These sites may represent a putative fission/fusion spot involved in the differentiation of G. humeralis-like 2n = 32 and C. amazonicus-like 2n = 36 karyotypes. Our results, especially on the location of Ag-NORs and the description of fragile sites, are relevant in improving our knowledge about the events of chromosome evolution in this extremely variable and poorly known group of lizards.
Chromosome banding and molecular cytogenetic study of two Mediterranean trachinoid fish species (Teleostei: Trachinidae, Uranoscopidae)
Authors: Caputo V. , Colomba M. , Nisi Cerioni P. , Vitturi R. , Giovannotti M. , Olmo E.
Published: March 2004

The chromosomes of Echiichthys vipera (Trachinidae) and Uranoscopus scaber (Uranoscopidae) were analyzed by means of various banding methods and fluorescence in situ hybridization (FISH) with telomeric and major rDNA probes, respectively. The karyotype of E. vipera was composed of 48 acrocentric chromosomes and NOR sites, as revealed by all detection methods, were situated pericentromerically on a single pair of middle-sized chromosomes. Blocks of constitutive heterochromatin were present in the pericentromeric regions of all pairs of chromosomes. The karyotype of U. scaber showed three karyomorphs: 2n = 30 (18 m + 12 a/st [m = metacentric, a = acrocentric and st = subtelocentric]), 2n = 28 (20 m + 8 a/st), 2n = 27 (21 m + 6 a/st). NORs, as revealed by FISH, were situated pericentromerically on a single pair of middle-sized chromosomes in spite of Ag-positive signals in the centromeres of all pairs of chromosomes. Robertsonian fusions were hypothesized for observed variation due to invariable number of chromosome arms FN = 48.
Cytogenetic mapping and orientation of the rhesus macaque MHC
Authors: Huber I. , Walter L. , Wimmer R. , Pasantes J.J. , Günther E. , Schempp W.
Published: March 2004

Applying fluorescence in situ hybridisation (FISH), six cosmid clones of rhesus macaque origin containing the genes SACM2L, RING1, BAT1 and MIC2, MIC3, MICD, and MOG of the major histocompatibility complex (MHC) were localised to the long arm of the rhesus macaque chromosome 6 in 6q24, the orthologous region to human 6p21.3. Furthermore, centromere to telomere orientation of the rhesus macaque MHC as well as the internal order of the MHC genes tested are the same as in human. Fiber-FISH allows a rough estimate of distances between these MHC genes in the rhesus macaque, and, as in the human, the rhesus macaque MHC comprises about 3 to 4 Mb.
The c-src1 gene visualized by in situ hybridization on Xenopus laevis chromosomes
Authors: Krylov V. , Mácha J. , Tlapáková T. , Takáč M. , Jonák J.
Published: March 2004

Fluorescent in situ hybridization followed by tyramide signal amplification was used to map the site of the c-src1 gene on Xenopus laevis chromosomes. Positive results were obtained with a cDNA probe of about 1 kb. The c-src1 gene is located in the subcentromeric region in the long arm of one of the acrocentric chromosomes of the G category (classified according to Graf and Kobel, 1991). The c-src1 gene and the Xenopus major histocompatibility complex (MHC) 1b locus, which consists of 20 tandemly arranged gene copies, are situated on different chromosomes of the G category.
Recombination nodules in coleopteran species: Palembus dermestoides (Tenebrionidae) and Epicauta atomaria (Meloidae)
Authors: Zacaro A.A. , de Almeida M.C. , Cella D.M.
Published: March 2004

This work describes the first report about the occurrence of recombination nodules (RNs) in spread pachytene cells of two species of Coleoptera: Palembus dermestoides (Tenebrionidae) and Epicauta atomaria (Meloidae). The RNs were observed in preparations contrasted with phosphotungstic acid. Considering RN morphology and its occurrence in pachytene bivalents (one per autosome bivalent) these structures were interpreted to be late RNs. P. dermestoides and E. atomaria have 2n = 20 chromosomes including an Xyp sex determination system. In spite of most frequently subtelocentric morphology observed in the autosomes of both species, the occurrence of RNs is limited only to the synaptonemal complex (SC) structure of the long arms. These findings are in agreement with those obtained using light microscopy analysis in which only one chiasma or terminalization event is observed per autosomal bivalent in early or late metaphase I cells. The RNs have the same average width of the SC of each analyzed species, a circular shape, strong electron density, and are observed mainly between the lateral elements of the SC. The RNs of P. dermestoides and E. atomaria have approximately the same average size (width), 180 ± 20 nm and 160 ± 80 nm, respectively. The absence of RNs in the short arms and its occurrence in the long arms are discussed considering the short arm pericentromeric and pro-centric heterochromatin.
Comparative chromosome painting of chicken autosomal paints 1–9 in nine different bird species
Authors: Guttenbach M. , Nanda I. , Feichtinger W. , Masabanda J.S. , Griffin D.K. , Schmid M.
Published: March 2004

In a Zoo-FISH study chicken autosomal chromosome paints 1 to 9 (GGA1–GGA9) were hybridized to metaphase spreads of nine diverse birds belonging to primitive and modern orders. This comparative approach allows tracing of chromosomal rearrangements that occurred during bird evolution. Striking homologies in the chromosomes of the different species were noted, indicating a high degree of evolutionary conservation in avian karyotypes. In two species, the quail and the goose, all chicken paints specifically labeled their corresponding chromosomes. In three pheasant species as well as in the American rhea and blackbird, GGA4 hybridized to chromosome 4 and additionally to a single pair of microchromosomes. Furthermore, in the pheasants fission of the ancestral galliform chromosome 2 could be documented. Hybridization of various chicken probes to two different chromosomes or to only the short or long chromosome arm of one chromosome pair in the species representing the orders Passeriformes, Strigiformes, and Columbiformes revealed translocations and chromosome fissions during species radiation. Thus comparative analysis with chicken chromosome-specific painting probes proves to be a rapid and comprehensive approach to elucidate the chromosomal relationships of the extant birds.
Mesangiocapillary Glomerulonephritis Type 2 Associated with Familial Partial Lipodystrophy (Dunnigan-Kobberling Syndrome)
Authors: Owen Katharine R. , Donohoe Mollie , Ellard Sian , Clarke Tom J. , Nicholls Anthony J. , Hattersley Andrew T. , Bingham Coralie
Published: March 2004

The lipodystrophies are a heterogeneous group of disorders of adipose tissue associated with insulin resistance. The sporadic form of partial lipodystrophy, characterised by fat loss from the face and upper body, is associated with complement abnormalities and mesangiocapillary glomerulonephritis type 2 (MCGN II) and the conditions are thought to have a shared autoimmune aetiology. We present the first case of the rare familial form of partial lipodystrophy, caused by a mutation in the LMNA gene, associated with MCGN II. This suggests that partial lipodystrophy of both the sporadic and familial subtypes may predispose to this condition and that the observed renal and complement abnormalities may be secondary to other factors associated with lipodystrophy.
The Efficacy and Safety of Reteplase for Thrombolysis of Hemodialysis Catheters at a Community and Academic Regional Medical Center
Authors: Hyman Gary , England Michael , Kibede Sosena , Lee Patti , Willets George
Published: March 2004

In occluded hemodialysis catheters, thrombolytic agents are used to dissolve fibrin clots, reestablish blood flow and allow the patient to continue with hemodialysis treatment. Prior to 2001, urokinase was the indicated fibrinolytic for hemodialysis catheter thrombolysis. However, when urokinase became unavailable in the United States, New Hanover Regional Medical Center developed and implemented a protocol for the use of another fibrinolytic, reteplase, to lyse catheter occlusions. The purpose of this retrospective analysis was to assess the safety and efficacy of reteplase in opening occluded catheters in a series of patients receiving hemodialysis. Between January 1 and June 30, 2002, 59 patients could not complete dialysis, because of either poor arterial blood flow or elevated venous resistance. Reteplase, 0.4 U, was administered to the lumen of occluded catheters. After 30 min dwell times, the lumens were aspirated. If flow could not be sufficiently reestablished, a second reteplase dose was administered. Efficacy endpoints were defined as the ability to complete hemodialysis and achieve flow rates of ≧250 ml/min. Safety endpoints were defined as the occurrence of allergic reactions or bleeding. Eighty-five percent (50/59) of the patients were able to complete their hemodialysis session following reteplase administration, with 70% (41/59) able to sustain blood flow rates of ≧250 ml/min. Of the 50 patients who successfully completed dialysis, 66% (33/50) required only one 0.4-unit dose of reteplase per lumen while 34% (17/50) required a second dose. No instances of bleeding or allergic reactions were noted.
Risk Factors of Nontunneled Noncuffed Hemodialysis Catheter Malfunction
Authors: Hryszko Tomasz , Brzosko Szymon , Mazerska Maria , Malyszko Jolanta , Mysliwiec Michal
Published: March 2004

Background: The use of noncuffed nontunneled central venous catheters is a widely accepted method of gaining temporary vascular access for hemodialysis. Malfunction and bacteremia are the main factors limiting catheter survival. Methods: We followed up prospectively 73 hemodialysis catheters (HC) (40 internal jugular, 33 femoral) in order to establish factors influencing HC malfunction. HC malfunction was defined as a catheter that was unable to attain and maintain blood flows of at least 150 ml/min. 73 HC were used for a total 1,100 days. Results: HC malfunction occurred in 23 cases (31.51%) during the study period, giving an overall rate of 21 episodes per 1,000 catheter days at risk. An analysis revealed a higher risk of HC malfunction with the catheterization of the femoral vein compared to the internal jugular vein (hazard ratio (HR) 6.3; 95% confidence interval (CI) 5.3–7.3). After correction for confounding factors in multivariate Cox analysis, the site of the catheterization remained a statistically significant predictor of HC malfunction (HR 5.03, 95% CI 3.83–6.23). After the first week malfunction rate was 42 and 8% for femoral and internal jugular site, respectively (relative risk (RR) for malfunction 5.3 (95% CI, 2.5–8). After the second and third week, the incidence of malfunction was 51 and 14% for femoral and internal jugular vein, respectively (RR 3.6, 95% CI 2.2–5.1). Conclusions: Catheterization of the internal jugular vein is associated with longer catheter survival when compared to the femoral vein. Hemodialysis catheters should be placed, if possible, in internal jugular vein to prevent their premature malfunction.
High Prevalence of Aortic Valve Alterations in Haemodialysis Patients Is Associated with Signs of Chronic Inflammation
Authors: Schönenberger Andrea , Winkelspecht Bernd , Köhler Hans , Girndt Matthias
Published: March 2004

Aims: Cardiovascular morbidity is high in chronic haemodialysis patients. Previous studies showed a relation between uraemia-associated inflammation and cardiovascular mortality. This study intends to relate chronic inflammation to ultrasonographic markers of atherosclerotic cardiac or vascular alterations. Methods: Complete echocardiographic status and sonography of the common carotid arteries with measurement of intima media thickness (IMT) was performed in 55 stable chronic haemodialysis patients and 15 patients with arterial hypertension and normal renal function (controls). C-reactive protein (CRP) was determined monthly. The number of cardiovascular events after initiation of haemodialysis treatment was recorded by analysis of the patient’s files. Results: Aortic valve sclerosis was found in 19 dialysis patients (34%) and 1 control (6%), haemodynamically relevant stenosis in additional 14 patients (25%) and 1 control. Carotid IMT thickening was frequent in both dialysis patients (38%) and controls (20%). Aortic stenosis was associated with chronically elevated CRP levels while aortic sclerosis and thickening of the carotid wall were not. Eleven patients had cardiovascular events in their history, tightly associated with chronically elevated CRP levels. Conclusions: Chronic inflammation in dialysis patients is associated with aortic valve stenosis and high prevalence of cardiovascular events but not with thickening of the carotid wall. This suggests pathogenetic differences between destructive vascular disease and arterial wall thickening.
Provider Use of Preventive Strategies for Radiocontrast Nephropathy in High-Risk Patients
Authors: Weisbord Steven D. , Bruns Frank J. , Saul Melissa I. , Palevsky Paul M.
Published: March 2004

Background/Aims: Radiocontrast nephropathy (RCN) is a common and costly form of acute renal failure. Current preventative strategies include the use of intravenous (IV) fluids and the discontinuation of nephrotoxic medications at the time of radiocontrast administration. We sought to determine whether providers employ these strategies in high-risk patients to limit the development of RCN. Methods: High-risk patients undergoing procedures using radiocontrast media over a 12-month period were identified. Medical records were reviewed for all subjects who developed RCN and a randomly selected 25% of patients without RCN. Patients with a contraindication to IV volume expansion were excluded. Medical records of the remaining patients were reviewed to determine whether IV fluids were administered and whether NSAIDs or COX-2 inhibitors were prescribed at the time of contrast administration. Results: RCN developed in 8% of patients overall. Of 144 patients eligible for IV volume expansion, 16% failed to receive any IV fluids. When IV fluids were employed, their dose and timing of administration varied significantly by treating specialty and procedure. NSAIDs and COX-2 inhibitors were prescribed to 8% of patients. Conclusions: Commonly accepted strategies for the prevention of RCN are underutilized. Quality improvement efforts are needed to increase the use of these two simple prophylactic measures.
Role of Thrombospondin-1 in the Autologous Phase of an Accelerated Model of Anti-Glomerular Basement Membrane Glomerulonephritis
Authors: Hochegger Kathrin , Knight Sara , Hugo Christian , Mayer Gert , Lawler Jack , Mayadas Tanya N. , Rosenkranz Alexander R.
Published: March 2004

Background: Thrombospondin-1 (TSP1), a multifunctional, extracellular matrix protein, regulates cellular attachment, proliferation, migration, and differentiation in vitro, and is expressed de novo in many inflammatory diseases, including glomerulonephritis (GN). Methods: We investigated the role of TSP1 in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) GN in mice deficient in TSP1. The model, induced by the injection of rabbit anti-mouse GBM antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. Results: Mice deficient in TSP1 developed significantly less proteinuria than their wild-type controls 21 days after induction of disease (5,793 ± 5,456 vs. 24,293 ± 15,336 µg albumin/mg creatinine; p = 0.002). Serum creatinine levels were significantly higher in the wild-type mice than in the TSP1 deficient animals (29.03 ± 2.34 vs. 16.39 ± 2.87 µmol/l; p = 0.005). Other disease indices as crescent formation, fibrin deposition and macrophage influx, were also diminished in the TSP1 knockout animals. The numbers of interstitial CD4+ and CD8+ T cells were generally less in TSP1-deficient mice and reached statistical significance in CD4+ (p = 0.01) and CD8+ T cells (p = 0.02). The difference in outcome of the disease was not due to the difference in deposition/production of heterologous and autologous antibodies in the two groups of animals. Conclusion: This study suggests a proinflammatory role of TSP1 in an experimental model of GN.
Differentiation-Induced Cultured Podocytes Express Endocytically Active Megalin, a Heymann Nephritis Antigen
Authors: Yamazaki Hajime , Saito Akihiko , Ooi Hidemi , Kobayashi Naoto , Mundel Peter , Gejyo Fumitake
Published: March 2004

Background/Aims: Megalin is a multiligand endocytic receptor expressed in a number of epithelia. In the Lewis rat kidney, podocytes, as well as proximal tubule cells, express megalin that acts as a pathogenic antigen for Heymann nephritis (HN), an experimental model of membranous nephropathy. To obtain a tool to investigate the molecular mechanisms of megalin-mediated endocytosis and the pathogenesis of HN, we examined whether a differentiation-inducible mouse podocyte cell line expressed endocytically active megalin. Methods: Immunofluorescence and immunoprecipitation analyses with an anti-rat megalin antibody were carried out to investigate whether megalin was expressed in the differentiated and undifferentiated podocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to elucidate whether the cells synthesize megalin mRNA. 125I-labeled receptor-associated protein (RAP), an endocytic ligand for megalin, was used for cellular internalization and degradation assays. Results: Immunofluorescence, immunoprecipitation and RT-PCR analyses revealed that megalin was synthesized in both differentiated and undifferentiated cells and localized to the cell surfaces. Effective endocytosis of RAP via megalin was shown under the differentiated condition. Conclusion: Endocytically active megalin is expressed in differentiation-induced cultured podocytes. This cell line could be a useful tool for studies on megalin-mediated endocytosis and the pathogenesis of HN.
Intracellular Cyclic Nucleotide Analogues Inhibit in vitro Mitogenesis and Activation of Fibroblasts Derived from Obstructed Rat Kidneys
Authors: Hewitson T.D. , Martic M. , Darby I.A. , Kelynack K.J. , Bisucci T. , Tait M.G. , Becker G.J.
Published: March 2004

As several studies indirectly suggest that inhibiting the intracellular breakdown of cyclic nucleotides may inhibit fibrogenesis, this study used membrane permeable cyclic nucleotide analogues to examine the role of cAMP and cGMP signaling pathways in the regulation of renal fibroblast function. Fibroblasts were isolated by explant outgrowth culture of rat kidneys post unilateral ureteric obstruction. Subcultured cells were exposed to 10– 1,000 µM of the cyclic nucleotide analogues 8-bromo-cAMP (8br-cAMP) and 8-bromo-cGMP (8br-cGMP). Functional parameters examined included mitogenesis (thymidine incorporation), collagen synthesis (proline incorporation), myofibroblast differentiation (Western blotting for α-smooth muscle actin; α-SMA) and expression of CTGF (Northern blotting), a TGF-β1-driven immediate early response gene. Serum-stimulated mitogenesis was decreased 27 ± 4% by 100 µM 8br-cAMP (p < 0.01), 49 ± 6% by 1,000 µM 8br-cAMP (p < 0.001) and 43 ± 7% by 1,000 µM 8br-cGMP (p < 0.01). 1,000 µM 8br-cAMP and 8br-cGMP reduced basal collagen synthesis by 80 ± 5 and 60 ± 21% respectively (both p < 0.05). Maximum dose of 8br-cAMP but not 8br-cGMP inhibited basal expression of the differentiation marker α-SMA by 43 ± 33 (p < 0.05), resulted in a more rounded cell morphology and reduced expression of CTGF by 39 ± 24% (p < 0.05). Measurement of mitochondrial activity confirmed that effects were independent of cell toxicity. In conclusion, cyclic nucleotides inhibit fibrogenesis in vitro. Strategies which elevate intracellular cyclic nucleotide concentrations may therefore be therapeutically valuable in preventing the proliferation and activation of fibroblasts in progressive renal disease.
Lipocalin-Type Prostaglandin D Synthase in Urine in Adriamycin-Induced Nephropathy of Mice
Authors: Tsuchida Takamasa , Eguchi Naomi , Eguchi Yutaka , Numabe Atsushi , Nakajima Hiroshi , Oda Hiroshi , Seiki Kousuke , Hakamada-Taguchi Rie , Urade Yoshihiro , Uehara Yoshio
Published: March 2004

Background/Aims: Lipocalin-type prostaglandin D synthase (L-PGDS), an enzyme converting prostaglandin H2 to prostaglandin D2, occurs particularly in the cardiovascular system. Urinary L-PGDS excretion is increased in diabetes prior to overt proteinuria, suggesting that it is a predictor of renal injury. In this study, we tested the hypothesis that L-PGDS excretion reflects renal injury in primary glomerular diseases using Adriamycin-induced nephropathy in mice. Methods: Twenty 6-week-old ICR female mice were intravenously given a dose of 25 mg Adriamycin/kg body weight through the tail vein. 24-hour urine was collected every day, and blood samples were obtained. Results: The mice developed significant albuminuria from day 3 onward (p < 0.05), which was followed by overt proteinuria from day 4 (p < 0.05). Histological examination revealed focal mesangial expansion with partial tubular atrophy. Urinary L-PGDS excretion significantly increased from day 1 onward (p < 0.05), and apparently preceded the increase in urinary albumin excretions. Either serum L-PGDS or creatinine levels were not changed by administration of Adriamycin. However, serum creatinine levels were inversely correlated to urinary L-PGDS excretions (r = –0.88, p < 0.05). Immunohistochemistry showed that L-PGDS occurred in the tubules, but not in the glomeruli in Adriamycin mice and L-PGDS mRNA paralleled urinary L-PGDS excretion. Conclusion: Urinary L-PGDS excretion is increased in Adriamycin-induced nephropathy, and this precedes overt albuminuria.
Protective Effects of B2 Preservation Solution in Comparison to a Standard Solution (Histidine-Tryptophan-Ketoglutarate/Bretschneider) in a Model of Isolated Autologous Hemoperfused Porcine Kidney
Authors: Fehrenberg Claudia , von Baeyer Hans , Unger Volker , Schmitt Roland , Haider Wolfram , Quarcoo David , Groneberg David A. , Grosse-Siestrup Christian
Published: March 2004

Reperfusion injuries after organ transplantation affect graft function and influence long-term graft survival. As hypothermic storage, which minimizes the extent of unspecific tissue injury after ischemia and reperfusion, is significantly influenced by the composition of preservation solutions, strategies to optimize the different components may lead to longer graft survival. In the present study the effects of the preservation solution B2 on early renal function and histopathological changes were compared to histidine-tryptophan-ketoglutarate solution (HTK, Bretschneider) in a model of isolated blood-perfused porcine kidneys. B2-preserved kidneys displayed a lower renal resistance and significantly better creatinine clearance as compared to HTK. Mean differences were also found for filtration fraction and sodium fraction reabsorption. The functional data were also related to histopathological changes. Together, these data indicate that the recently developed preservation solution B2 offers new principles of preservation and is a useful preservation solution for experimental isolated perfused kidney models. B2 may also be an interesting model for optimizing preservation within other organ perfusion models.
Paroxetine Decreases Respiratory Irregularity of Linear and Nonlinear Measures of Respiration in Patients with Panic Disorder
Authors: Yeragani Vikram Kumar , Rao Radhakrishna , Tancer Manuel , Uhde Thomas
Published: March 2004

Previous studies indicate that serotonin reuptake inhibitors do not appear to have serious cardiac side effects. However, the effects of these agents on respiratory measures have not been studied in detail. Several studies indicate that patients with anxiety exhibit irregular breathing patterns as measured by tidal volume and respiratory rate. In this study, we evaluated the effects of a serotonin reuptake inhibitor, paroxetine, on respiratory variability in patients with panic disorder (n = 13), using linear and nonlinear measures of regularity, approximate entropy (APEN) and a measure of chaos, the largest Lyapunov exponent (LLE), with pre- and posttreatment lung volume time series (256 s long sampled at 4 Hz). Our results show that paroxetine significantly decreases some of the linear measures of variability and supine APEN and standing LLE of lung volume series after successful treatment. The implications of these findings on respiratory and cardiovascular function have been discussed.
Asperger Syndrome, Alexithymia and Perception of Sleep
Authors: Tani Pekka , Lindberg Nina , Joukamaa Matti , Nieminen-von Wendt Taina , von Wendt Lennart , Appelberg Björn , Rimón Ranan , Porkka-Heiskanen Tarja
Published: March 2004

Two research traditions, the one on Asperger syndrome (AS) and the other on alexithymia, have produced similar findings independently of each other indicating a possible association between these two phenomena. Both conditions are also associated with impaired initiation and continuity of sleep. Twenty AS adults were compared with 10 healthy controls using the Toronto Alexithymia Scale and the Basic Nordic Sleep Questionnaire. AS subjects were significantly more alexithymic and reported lower sleep quality as compared with controls. AS and alexithymia are associated although the mediating factors are unknown. It is possible that alexithymic traits predispose to anxiety, which in turn lowers the sleep quality in AS adults. Alternatively, low sleep quality might be due to AS itself.