bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Cerebral Blood Flow Velocity as Measured in Preeclamptic, Healthy Pregnant, and Nonpregnant Women by Transcranial Doppler Sonography
Authors: Zatik János , Aranyosi János , Mihálka László , Páll Dénes , Major Tamás , Fülesdi Béla
Published: April 2003

Aim: To test the hypothesis that the middle cerebral artery blood flow velocity (MCAV) is altered in preeclamptic pregnant women as compared with healthy pregnant and nonpregnant women. Methods: Preeclamptic (n = 21) and healthy pregnant (n = 17) as well as healthy nonpregnant (n = 29) women underwent transcranial Doppler MCAV measurements. The mean MCAV values were compared between the different groups. Anova combined with Bonferroni correction was used for statistical analysis. Results: The MCAV was significantly higher in nonpregnant women (mean ± SE 73.0 ± 2.12 cm/s) as compared with healthy pregnant women (67.0 ± 1.8 cm/s, p = 0.0356). Preeclamptic women showed significantly higher MCAV values (83.5 ± 2.1 cm/s) as compared with nonpregnant females (73.0 ± 2.12 cm/s, p = 0.0014). Similar to nonpregnant women, healthy pregnant women showed lower MCAV values (67.0 ± 1.8 cm/s) as compared with preeclamptic women (83.5 ± 2.1 cm/s, p = 0.001). After Bonferroni correction the MCAV values in patients suffering from preeclampsia were still statistically significantly higher as compared with the two other groups. Conclusions: We detected increased resting MCAV values in pregnant women with preeclampsia. In our opinion, this finding refers to arteriolar dilation of the resistance vessels of the brain. Further studies are needed to prove altered vasoreactivity responses of the brain resistance arterioles in preeclampsia.
Oxidative DNA Damage and Tubulointerstitial Injury in Diabetic Nephropathy
Authors: Kanauchi Masao , Nishioka Hisayuki , Hashimoto Toshio
Published: April 2003

Background: Oxidative stress is an important pathogenetic factor in underlying diabetic complications. Recently, 8-hydroxy-2′-deoxyguanosine (8-OHdG) has been reported to serve as a new sensitive biomarker of the oxidative DNA damage in vivo. We studied the relationship between oxidative DNA damage and tubulointerstitial injury in patients with diabetic nephropathy. Methods: Type 2 diabetic patients (n = 25) and healthy control subjects (n = 20) were studied. The urine concentrations of 8-OHdG were measured by a competitive ELISA. The severity of the glomerular changes was graded using Gellman’s criteria, and the severity of the tubulointerstitial lesions was determined by a semiquantitative estimate of the space occupied by the fibrous tissue and/or interstitial infiltrates. Results: The urinary 8-OHdG excretion were significantly higher in the diabetics than in the healthy controls, and tended to increase with severity of the glomerular diffuse lesion, but it was not significant. The urinary 8-OHdG excretion significantly increased with severity of the tubulointerstitial lesion. Conclusions: Oxidative stress may contribute to the progression of tubulointerstitial injury in patients with diabetic nephropathy.
Distribution of MLH1 foci on the synaptonemal complexes of chicken oocytes
Authors: Pigozzi M.I.
Published: April 2003

The frequency and distribution of the mismatch repair protein MLH1 was analyzed on synaptonemal complex spreads of chicken oocytes using indirect immunofluorescence. MLH1 foci appeared in late zygotene and their number remains constant throughout pachytene. The average number of foci on autosomal synaptonemal complexes (65.02 ± 4.02) is in agreement with the number of chiasmata estimated from lampbrush chromosomes. The distribution of foci along the synaptonemal complexes is shown to be nonrandom and nonuniform in terms of the distances between them. It is concluded that MLH1 foci are good markers of crossing over in bird (chicken) meiocytes.
Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome
Authors: Wang Q. , Timur A.A. , Szafranski P. , Sadgephour A. , Jurecic V. , Cowell J. , Baldini A. , Driscoll D.J.
Published: April 2003

Klippel-Trenaunay syndrome (KTS) is a disorder primarily characterized by capillary-venous vascular malformations associated with altered limb bulk and/or length. We report the identification of a balanced translocation involving chromosomes 8q22.3 and 14q13 in a patient with a vascular and tissue overgrowth syndrome consistent with KTS. We demonstrated that translocation t(8;14)(q22.3;q13) arose de novo. These data suggest that a pathogenic gene for a vascular and tissue overgrowth syndrome (KTS) may be located at chromosome 8q22.3 or 14q13. Fluorescence in situ hybridization (FISH) analysis was used to define the breakpoint on chromosome 8q22.3 to a <5-cM interval flanked by markers AFMA082TG9 and GATA25E10, and the 14q13 breakpoint within a 1-cM region between STSs WI-6583 and D14S989. This study provides a framework for the fine-mapping and ultimate cloning of a novel vascular gene at 8q22.3 or 14q13.
A case of azoospermia in a bull carrying a Y-autosome reciprocal translocation
Authors: Iannuzzi L. , Molteni L. , Di Meo G.P. , de Giovanni A. , Perucatti A. , Succi G. , Incarnato D. , Eggen A. , Cribiu E.P.
Published: April 2003

During normal cytogenetic investigations on the Chianina cattle (BTA) breed, a normal looking young bull was found to carry an abnormal Y chromosome which was a product of a reciprocal translocation between chromosomes Y and 9. This was revealed by both CBA- and RBG-banding techniques and was clearly confirmed by FISH-mapping analysis with IDVGA50 (which paints the complete Yq arm in a normal Y), as well as with AMD1, CGA, IGF2R (mapping to BTA9q16, BTA9q22 and BTA9q27→q28, respectively) and SRY (mapping to normal BTAYq23). Analysis on sperm from four different samples revealed azoospermia in the carrier, indicating that the rcp(Y;9) induces sterility in the bull.
Regulation of Corticotropin-Releasing Factor Receptor Type 2β Messenger Ribonucleic Acid by Interleukin-1β in Rat Vascular Smooth Muscle Cells
Authors: Kageyama Kazunori , Suda Toshihiro
Published: April 2003

Objective: Corticotropin-releasing factor receptor type 2 (CRF R2) messenger RNA (mRNA) expression in the rodent heart or vessels is modulated by exposure to urocortin and glucocorticoids. In addition, we previously found that incubation with a variety of cytokines, such as interleukin (IL)-1 and IL-6, and tumor necrosis factor-α also reduced CRF R2β mRNA expression, with IL-1β being the most effective. In this study, we further explored the regulation of CRF R2β mRNA levels by IL-1β in the rat vascular smooth muscle A7r5 cells. Methods: A7r5 cells were incubated with IL-1β, urocortin, or both for 6 h, after pre-incubating with or without anti-IL-1β antibody (Ab) for 30 min, and then CRF R2β mRNA levels were measured by RNase protection assay. Cells were incubated with lipopolysaccharides, IL-1β, IL-6 , dexamethasone, forskolin, or urocortin for 20 min, and then intracellular cAMP was measured by cAMP RIA. Results: IL-1β produced a significant time-dependent decrease in CRF R2β mRNA levels. Combined urocortin and IL-1β administration did not have synergistic effects on the decrease in CRF R2β mRNA levels. IL-1β Ab failed to block the ability of urocortin to regulate CRF R2β mRNA levels, suggesting that urocortin regulated CRF R2β mRNA levels via another pathway than IL-1β production. Urocortin induced the intracellular cAMP production in A7r5 cells, while IL-1β failed to induce it. Conclusion: The multifactorial regulation of CRF R2β mRNA expression in the A7r5 cells serves to limit the inotropic and chronotropic effects of CRF R2 agonists such as urocortin during prolonged physical or immune challenge.
Biphasic Autoregulation of Mineralocorticoid Receptor mRNA in the Medial Septal Nucleus by Aldosterone
Authors: Hansson Anita C. , Fuxe Kjell
Published: April 2003

The time-dependent action of aldosterone was analyzed on the regulation of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNAs in the brain. Bilaterally adrenalectomized rats were injected subcutaneously with a single low dose of aldosterone (0.01 mg/kg, s.c.). By means of in situ hybridization MR and GR mRNA levels were studied in autoradiograms 2, 4, 8 and 24 h after the hormone injection in brain regions related to stress responses, i.e. subregions of the dorsal hippocampus (CA1 to CA4 and dentate gyrus), the hypothalamic paraventricular nucleus, and the septum. The findings show a biphasic regulation of MR mRNA levels in the medial septal nucleus with substantial increases after 4 h (79% increase) followed by substantial decreases in MR mRNA levels after 24 h (71% decrease), whereas no changes in MR mRNA levels were observed in the lateral septal nucleus. A negative autoregulation of hippocampal MR mRNA levels was observed only in the CA2 subregion (38% decrease) at the 8-hour time interval. Over the same time interval a negative cross-regulation of GR mRNA by aldosterone was observed in all hippocampal subfields (32–57% decrease) except in CA2. No changes in GR mRNA levels were found in the hypothalamic paraventricular nucleus. The time-dependent action of corticosterone (10 mg/kg, s.c.) was analyzed in the same animal model revealing no changes in MR mRNA levels in the medial and lateral septal nuclei. The present findings suggest that the medial septal nucleus shows a unique responsiveness to aldosterone in the adrenalectomized model in terms of biphasic changes in MR mRNA levels. Activated MR in the medial septal nucleus may therefore take part in the regulation of septo-hippocampal cholinergic pathways and thus of limbic circuits.
Detection of Genetic Alterations in Pancreatic Cancers by Comparative Genomic Hybridization Coupled with Tissue Microdissection and Degenerate Oligonucleotide Primed Polymerase Chain Reaction
Authors: Harada Tomohiko , Okita Kiwamu , Shiraishi Kei , Kusano Noriyoshi , Furuya Tomoko , Oga Atsunori , Kawauchi Shigeto , Kondoh Satoshi , Sasaki Kohsuke
Published: April 2003

The aim of this study was to elucidate cytogenetic changes in pancreatic cancers (PCs) and to examine their clinical implications. We screened for genetic alterations in 32 primary PCs including 4 cases with distant organ metastasis using comparative genomic hybridization coupled with tissue microdissection and degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). The present study revealed frequent gains of chromosomes 13q and 15q and a loss of Xq in addition to a high prevalence of chromosomal imbalances. The average number of total genetic alterations and gains tended to be higher in N1 tumors (TNM classification) than in N0 tumors. The average number of amplifications was significantly higher in M1 tumors than in M0 tumors (p = 0.024). Gain/amplification of 20q was more frequently observed in M1 tumors than in M0 tumors (p = 0.016), and this change was also detected in all of 4 distant metastatic lesions. Losses of 6q, 8p, 9p, 17p, and 18q were recurrent in N0 and M0 tumors, and these alterations were also retained in N1 and M1 tumors. These observations suggest that these genetic losses contribute to the development of PCs and that increases in the DNA copy number confer an aggressive character on cancer cells. Especially, gain/amplification of 20q was associated with the potential of distant organ metastasis of tumor cells.
Study of Psychopathology in Patients with Chronic Non-Lesional Epilepsy: A Minnesota Multiphasic Personality Inventory Profile Controlled Study
Authors: Modrego P.J. , Pina M.A. , Galindo M. , Mínguez J.
Published: April 2003

Objective: Psychiatric morbidity and psychopathology have been widely assessed in patients with epilepsy. However, the issue of whether people with epilepsy are at increased risk for psychopathology remains highly controversial. These disorders are not evaluated in a systematic manner in patients with non-lesional epilepsy, so they could be underestimated. The objective is to evaluate personality disorders in patients with non-lesional epilepsy. Methods: In this study, we investigated the presence of personality disorders in 63 patients with chronic non-lesional (idiopathic and cryptogenic) epilepsy and in 40 unrelated and randomly selected controls by means of Minnesota Multiphasic Personality Inventory (MMPI) and DSM-IV criteria for the different personality disorders. Results: The overall scores were significantly higher in the patients in the subscales of schizophrenia, depression, hysteria, mania, paranoia, psychasthenia and psychopathic deviate. However, the differences in the proportion of patients with clinically significant scores occurred only for schizophrenia (57 vs. 20%), depression (55 vs. 15%), psychasthenia (28 vs. 10%) and paranoia (14 vs. 0%). According to DSM-IV criteria, only 11 patients met the criteria of schizotypal personality. We found excellent concordance for paranoid personality and depression between the two instruments of diagnosis. However, we did not find cases with either antisocial or avoidant personality. We also found a significant link between poor control of epilepsy and high scores in both paranoia and psychopathic deviate. Conclusions: In comparison with the DSM-IV criteria for such personality disorders, the MMPI was oversensitive in detecting schizotypal features. However, the MMPI correctly classified the remaining personality disorders, especially depression and paranoid personality. On the basis of these results, we conclude that psychopathology is overrepresented in patients with chronic non-lesional epilepsy and that, in determined variables, this is due to the severity of the condition rather than to the type and duration of epilepsy. The approach to patients with chronic epilepsy should include neurobehavioural scales.
Kinesthetic Alexia due to Left Parietal Lobe Lesions
Authors: Ihori Nami , Kawamura Mitsuru , Araki Shigeo , Kawachi Juro
Published: April 2003

To investigate the neuropsychological mechanisms of kinesthetic alexia, we asked 7 patients who showed kinesthetic alexia with preserved visual reading after damage to the left parietal region to perform tasks consisting of kinesthetic written reproduction (writing down the same letter as the kinesthetic stimulus), kinesthetic reading aloud, visual written reproduction (copying letters), and visual reading aloud of hiragana (Japanese phonograms). We compared the performance in these tasks and the lesion sites in each patient. The results suggested that deficits in any one of the following functions might cause kinesthetic alexia: (1) the retrieval of kinesthetic images (motor engrams) of characters from kinesthetic stimuli, (2) kinesthetic images themselves, (3) access to cross-modal association from kinesthetic images, and (4) cross-modal association itself (retrieval of auditory and visual images from kinesthetic images of characters). Each of these factors seemed to be related to different lesion sites in the left parietal lobe.
Sleep Laboratory Diagnosis of Restless Legs Syndrome
Authors: Michaud Martin , Paquet Jean , Lavigne Gilles , Desautels Alex , Montplaisir Jacques
Published: April 2003

Polysomnographic recordings and the Suggested Immobilization Test (SIT) are frequently used to support the clinical diagnosis of restless legs syndrome (RLS). The present study evaluated the discriminant power of 5 different parameters: (1) index of periodic leg movements during sleep (PLMS), (2) index of PLMS with an associated microarousal (PLMS-arousal), (3) index of PLM during nocturnal wakefulness (PLMW), (4) SIT PLM index and (5) mean subjective leg discomfort score during the SIT (SIT MDS) in 100 patients with idiopathic RLS and 50 healthy control subjects. Both groups differed significantly on each parameter studied. Furthermore, while the SIT PLM, the PLMS and the PLMS-arousal indices revealed a poor ability to discriminate patients from controls, the PLMW index and the MDS both showed high sensitivity (87 ± 7 and 82 ± 8, respectively) and specificity (80 ± 11 and 84 ± 10, respectively) for diagnosing RLS. The combination of these 2 parameters correctly classified 88% of all subjects with a sensitivity of 82% and a specificity of 100%.
In situ hybridization and chromosome banding in mammalian species
Authors: Chaves R. , Adega F. , Santos S. , Guedes-Pinto H. , Heslop-Harrison J.S.
Published: April 2003

Chromosome banding is often required in conjunction with fluorescent in situ hybridization of labelled probes for chromosome painting, satellite DNA and low-copy sequences to allow identification of chromosomes and simultaneous probe localization. Here, we present a method that reveals both patterns with only one observation step. The band pattern is produced by restriction-enzyme digestion of chromosomes, followed by fixation with paraformaldehyde in PBS, a short chromosome denaturation step in hybridization solution, and then standard in situ hybridization, washing and detection protocols. Using a range of different mammalian species, chromosome-banding patterns were immediately recognizable, although synchronisation procedures normally required for high- resolution G-banding were not needed. Unlike other methods available, only one round of observation is required using a conventional fluorescence microscope, the method works without modification in many species, and in situ hybridization is not used for chromosome identification (allowing multiple targets and minimizing background). The banding pattern is probably generated by a combination of DNA dissolution and heterochromatin reorganisation after enzyme digestion, followed by paraformaldehyde fixation of the new chromatin structure and incomplete denaturation. The method is of widespread utility in comparative genomics and genome organization programmes.
Meiotic studies of male common shrews (Sorex araneus L.) from a hybrid zone between chromosome races
Authors: Banaszek A. , Fedyk S. , Fiedorczuk U. , Szałaj K.A. , Chetnicki W.
Published: April 2003

Thirty-three adult male common shrews (Sorex araneus L.) were collected from a hybrid zone between two chromosomal races that differed in Robertsonian metacentrics. Anaphase I nondisjunction frequencies were estimated on the basis of metaphase II counts. RIV and CV complex heterozygotes (four-element rings and five-element chains at meiosis I, respectively) had substantially higher nondisjunction rates than homozygotes and simple Robertsonian heterozygotes. However, at least in the case of RIV-forming hybrids, increased nondisjunction frequency did not result from malsegregation of the heterozygous complex. Extra elements found in hyperploid spreads were most frequently acrocentrics, that could not originate from a fully metacentric multivalent. Complex heterozygotes were also characterized by higher frequencies of univalents observed at diakinesis I. However, univalents did not originate from complex configurations, which were regularly formed with usually one chiasma per chromosome arm. Hence, we suppose that the presence of multivalents in the cell affects pairing and segregation of other elements at meiosis I.
Alps, genes, and chromosomes: their role in the formation of species in the Sorex araneus group (Mammalia, Insectivora), as inferred from two hybrid zones
Authors: Brünner H. , Lugon-Moulin N. , Hausser J.
Published: April 2003

During the Pleistocene glaciations, the Alps were an efficient barrier to gene flow between isolated populations, often leading to allopatric speciation. Afterwards, the Alps strongly influenced the post-glacial recolonization of Europe and represent a major suture zone between differentiated populations. Two hybrid zones in the Swiss and French Alps between genetically and chromosomally well-differentiated species—the Valais shrew, Sorex antinorii, and the common shrew, S. araneus—were studied karyotypically and by analyzing the distribution of seven microsatellite loci. In the center of the Haslital hybrid zone the two species coexist over a distance of 900 m. Hybrid karyotypes, among them the most complex known in Sorex, are rare. F-statistics based on microsatellite data revealed a strong heterozygote deficit only in the center of the zone, due to the sympatric distribution of the two species with little hybridization between them. Structuring within the species (both FIS and FST) was low. An hierarchical analysis showed a high level of interspecific differentiation. Results were compared with those previously reported in another hybrid zone located at Les Houches in the French Alps. Genetic structuring within and between species was comparable in both hybrid zones, although chromosomal incompatibilities are more important in Haslital, where a linkage block of the race-specific chromosomes should additionally impede gene flow. Evidence for a more restricted gene flow in Haslital comes from the genetically intermediate hybrid karyotypes, whereas in Les Houches, hybrid karyotypes are genetically identical to individuals of the pure karyotypic races. Genic and chromosomal introgression was observed in Les Houches, but not in Haslital. The possible influence of a river, separating the two species at Les Houches, on gene flow is discussed.
Comparative mapping in equids: the asine X chromosome is rearranged compared to horse and Hartmann’s mountain zebra
Authors: Raudsepp T. , Lear T.L. , Chowdhary B.P.
Published: April 2003

The X chromosomes of the extant equids, in general, share morphology and banding pattern similarities. However, the donkey X is, in part, an exception because of significantly different centromeric index and variant banding patterns in the pericentromeric region. To verify the underlying molecular basis of this difference, twelve equine BAC clones were FISH mapped to donkey (EAS) and Hartmann’s mountain zebra (EZH) metaphase spreads. Loci from the terminal region of Xp and distal to terminal regions of the Xq showed the same order and relative position in all three species, implying cross-species conservation of these chromosomal segments. However, loci from the proximal/pericentromeric regions of either arms showed similar FISH locations in horse and zebra but a slightly deviant location and relative position in the donkey. Three of the markers (tel–OTC, TRAP170 and psALDH2– cen) located on the short arm of ECAX and EZHX were found inverted on the long arm of EASX, along with the transposition of the centromere. This molecular evidence of a pericentromeric inversion helps define the likely evolutionary breakpoints causing the rearrangement. The breakpoints most likely correspond to the region between Xp16→q12 in the horse and Xp12→q13 in the donkey. The findings coupled with the highly conserved X-chromosome gene order between horse and outgroup species, human and cat, suggest that the equine type X is ancestral while the asine type X arose as a result of an independent inversion event. The study adds two new markers to horse, 11 to donkey and 12 to Hartmann’s zebra gene maps, thus contributing to the expansion of comparative maps in the equids.
Routine Screening of (--SEA) α-Thalassemia Deletion by an Enzyme-Linked Immunosorbent Assay for Embryonic ζ-Globin Chains
Authors: Ma S.K. , Ma Victor , Chan Amy Y.Y. , Chan L.C. , Chui David H.K.
Published: April 2003

We evaluated an enzyme-linked immunosorbent assay (ELISA) for embryonic ζ-globin chains as a routine screening test for (--SEA) α-thalassemia deletion (SEA deletion). A total of 174 consecutive patient samples with a request for Hb analysis were recruited. The ELISA method was evaluated against a polymerase chain reaction (PCR)-based technique that was taken as the standard. Among 56 simple carriers of SEA deletion diagnosed by PCR and 112 subjects without the SEA deletion, the sensitivity and specificity of the ELISA method was 89.3–96.4 and 98.2–100%, respectively, depending on the cutoff value for optical density that was adopted. The ELISA method was able to detect both subjects with SEA deletion and concurrent β-thalassemia trait in this series, but only 1 out of 4 patients (25%) with Hb H disease. We speculate that incomplete lysis of hypochromic microcytic red cells together with the low red cell count in Hb H disease might account for the false-negative results. We showed that the ELISA method for embryonic ζ-chains was a sensitive method of screening for SEA deletion carriers at our locality, and should be easily adopted in a routine diagnostic laboratory. The method was rapid and also amendable to automation. In areas with a high prevalence of α-thalassemia, improved detection of SEA deletion carriers would ultimately facilitate the identification of pregnancies at risk of hydrops fetalis and its prevention through prenatal diagnosis.
Effects of Ornithine α-Ketoglutarate on Circulatory Antioxidants and Lipid Peroxidation Products in Ammonium Acetate Treated Rats
Authors: Dakshayani K.B. , Velvizhi S. , Subramanian P.
Published: April 2003

The effects of ornithine α-ketoglutarate (OKG) on ammonium acetate induced hepatotoxicity were studied biochemically in rats. The levels of urea, nonprotein nitrogen, and thiobarbituric acid reactive substances were significantly increased in ammonium acetate treated rats; these levels were significantly decreased in rats treated with ammonium acetate and OKG. Similar patterns of alterations were observed in the levels of free fatty acids, triglycerides, and phospholipids. Furthermore, nonenzymatic antioxidants (vitamins C and E) were significantly decreased in ammonium acetate treated rats, when compared with control rats, and increased in OKG and ammonium acetate treated rats. The biochemical alterations during OKG treatment could be (1) by detoxifying excess ammonia; (2) by participating in nonenzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process, and (3) by enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus prevent the lipid peroxidative damages in rats.
The Risk of Obesity and the Trp64Arg Polymorphism of the β3-Adrenergic Receptor: Effect Modification by Age
Authors: Corbalán M.S. , Marti A. , Forga L. , Martínez-Gonzalez M.A. , Martínez J.A.
Published: April 2003

Aim: To examine the association between the risk of obesity and the Trp64Arg polymorphism of the β3-adrenergic receptor gene. Methods: A case-control study was conducted. The case series encompassed 159 subjects with a body mass index >30 kg/m2 (obesity) and no other major diseases except for type 2 diabetes, and the controls were 154 healthy subjects with a body mass index <25 kg/m2. 313 Spanish subjects between 20 and 60 years of age were screened for the Trp64Arg mutation. Results: The prevalence of the Trp64Arg mutation was similar among cases (19.5%) and control subjects (16.2%). The association between the risk of obesity and the Trp64Arg mutation was estimated using multivariate logistic regression. A higher odds ratio of 3.84 (95% CI 1.33–11.12) for the mutation was found among younger individuals (20–35 years), while no increased risk was apparent among older participants (35–60 years). Moreover, when the model was adjusted for gender, age, and leisure-time physical activity, the product-term for interaction (effect modification) between age and the presence of the Trp64Arg mutation was statistically significant (likelihood ratio test p = 0.035). Conclusion: Individuals aged 20–35 years who are Trp64Arg carriers had a substantially higher risk of developing obesity, independent of their sex or leisure-time physical activity.
Leptin in the Newborn Mouse
Authors: Oden Jon , Fleenor Don , Driscoll Phyllis , Freemark Michael
Published: April 2003

Previous studies suggested that brown adipose tissue (BAT) provides a source of circulating leptin in the newborn mouse. However, we detected no leptin mRNA in newborn BAT or in newborn liver or stomach. In contrast, leptin expression was detected readily in newborn white adipose tissue (WAT). Fasting plasma leptin concentrations in newborn mice were comparable to those in adult nonpregnant mice. In contrast to adult mice, however, the fasting leptin levels in newborn males were comparable to those in females. While leptin in the late-gestational pregnant mouse circulates as a complex with the leptin-binding protein, leptin in the newborn mouse circulates as the free hormone. Factors regulating the expression of leptin by newborn WAT remain to be elucidated.
Effect of Intrauterine Ischemia-Hypoxia on Endothelial Nitric Oxide Synthase in Fetal Brain in Rats
Authors: Nakata Masahiko , Anno Kikue , Sugino Norihiro , Tashima Matsumori Lena , Nakamura Yasuhiko , Kato Hiroshi
Published: April 2003

Nitric oxide (NO) plays important roles in the regulation of cerebral blood flow (CBF) in the perinatal period. The present study was undertaken to investigate the influence of intrauterine ischemia-hypoxia (IH) on the expression of endothelial NO synthase (eNOS) in fetal brains in rats. To induce intrauterine IH insult, bilateral uterine arteries were ligated on day 17 of pregnancy. Activities and mRNA levels in the brain of the fetuses were examined on days 17–21 of pregnancy. The IH insult caused the increase in both activities and mRNA levels of eNOS on day 21 of pregnancy, whereas there were no significant changes in neuronal NOS mRNA levels. Endothelial NOS expression in the fetal brains was increased by intrauterine IH insult, suggesting that eNOS may contribute to the maintenance of CBF against ischemia or hypoxia conditions in the fetal rats.
Subclavian Coronary Steal Syndrome: An Obligatory Common Fate between Subclavian Artery, Internal Mammary Graft and Coronary Circulation
Authors: Elian Dan , Gerniak Alexander , Guetta Victor , Jonas Michael , Agranat Oren , Har-Zahav Yedael , Rath Shmuel , Di Segni Elio
Published: April 2003

The long-term patency of the left internal mammary artery (IMA) has made it the preferred conduit for myocardial revascularization. The proximal segment of the subclavian artery becomes functionally connected to the coronary circulation as a result of IMA implantation during coronary artery bypass surgery. The subclavian coronary steal syndrome results from stenosis in the left subclavian artery proximal to the IMA, compromising blood flow to the myocardium. We describe 7 patients, aged 55–75 years, 1.7–10.5 years after coronary bypass who presented with recurrent angina due to subclavian artery stenosis. The IMA graft was found open in each patient. A true steal mechanism was not demonstrated, casting doubt on the syndrome’s traditional name. Angioplasty and stenting of the subclavian artery resulted in the immediate disappearance of angina and continuous benefit at a follow-up of 3–32 months. The subclavian coronary steal syndrome, although rare, is a severe condition readily treated by angioplasty and stenting.
Successful Fetal Intervention for Congenital High Airway Obstruction Syndrome
Authors: Paek Bettina W. , Callen Peter W. , Kitterman Joseph , Feldstein Vickie A. , Farrell Jody , Harrison Michael R. , Albanese Craig T.
Published: April 2003

Introduction: Complete congenital high airway obstruction syndrome (CHAOS) usually leads to stillbirth or death within minutes of delivery. We describe the management and long-term follow-up of a baby with a prenatally diagnosed airway obstruction. Case: Because of progressive hydrops fetalis, massive ascites and everted diaphragms due to CHAOS in a fetus at 24 weeks of gestation, a fetal tracheostomy was performed. Persistent fetal bradycardia at the time of the fetal procedure led to delivery of the infant. Adequate oxygenation and ventilation were attained using relatively low oxygen concentrations and low ventilatory pressures. Plain radiographs demonstrated that the lungs were large and the ribs thin. The infant has a permanent tracheostomy, required continuous assisted ventilation for several months and assisted ventilation at night at home for 3 years. At 4 years of age, he has no speech, all feedings are by gastrostomy, and developmentally he is mildly to moderately delayed. Conclusion: Laryngeal atresia produced over-distended lungs and hydrops. Precise prenatal imaging and fetal surgical strategies may allow the survival of affected fetuses.
Delayed-Interval Delivery of Triplet Pregnancy following Preterm Labor
Authors: Kursun Sinan , Simsek Mehmet , Trak Bilal , Boneval Cem , Melikoglu Mustafa , Taskin Omur
Published: April 2003

Patients with multiple pregnancies have an increased risk of preterm labor and delivery with the associated high prenatal morbidity and mortality. Obviously, as the number of multifetal pregnancies increases (due primarily to the use of assisted reproductive treatments), a rise in the unexpected birth of one or more siblings at premature or previable stages is observed. In multiple pregnancies with imminent preterm birth, delayed delivery may offer survival chances and a favorable outcome for the remaining fetus(es). Herein, we report on the prolongation of a triplet pregnancy and survival of fetuses B and C after loss of fetus A at 21 weeks’ gestation.
Prenatal Diagnosis of Partial Anomalous Pulmonary Venous Connection by Detection of Dilatation of Superior Vena cava in Hypoplastic Left Heart
Authors: Respondek-Liberska Maria , Janiak Katarzyna , Moll Jadwiga , Ostrowska Katarzyna , Czichos Ewa
Published: April 2003

A 27-week fetus was given targeted fetal echocardiography due to an abnormal four-chamber view. A complex heart malformation was seen with two atria, a single ventricle, and aortic and mitral atresia. In addition to intracardiac findings, a dilated superior vena cava (SVC) was seen, suggesting a possible abnormal pulmonary venous connection to the SVC. An increased venous flow (up to 90 cm/s) was recorded as well. The course of pregnancy was uneventful and the baby was delivered vaginally at term. Cardiac surgery was planned but the baby died on 4th day of life. The autopsy findings confirmed both intracardiac anomalies as well as partial anomalous venous connection to SVC, with no apparent obstruction. This is the first report which stresses that dilatation of the fetal SVC may be suspicious for partial abnormal pulmonary venous connection during prenatal life.
Perceptions of the Impact of Speech, Language, Swallowing, and Hearing Difficulties on Quality of Life of a Group of South African Persons with Multiple Sclerosis
Authors: Klugman Tanya M. , Ross Eleanor
Published: April 2003

The present study investigated perceptions of speech, language, swallowing, and hearing difficulties and the relative impact of these problems on quality of life (QOL) in a group of South African persons with multiple sclerosis (MS). A questionnaire was used to elicit information regarding the difficulties experienced and the perceptions of their influence on QOL. Of the 30 respondents, 56.7% experienced speech problems and 63.3% reported language difficulties, with 62% of those feeling that these speech and language difficulties impacted on QOL. Fifty percent reported swallowing problems with 53% of those perceiving an influence on QOL. Twenty-three percent of participants experienced hearing problems with 44% expressing the view that their QOL was influenced. These findings are discussed with regard to their implications for the education and counselling of individuals with MS and their families, incorporation of speech-language pathologists and audiologists into management teams, and further research.
Bacterial Adhesiveness: Effects of the SH Metabolite of Erdosteine (Mucoactive Drug) plus Clarithromycin versus Clarithromycin Alone
Authors: Braga P.C. , Zuccotti T. , Dal Sasso M.
Published: April 2003

After metabolization, erdosteine (a mucoactive drug) produces an active metabolite (Met I) with an SH group that is capable of opening disulphide bonds, including those of pilin, a protein of bacterial fimbriae. This induces stereochemical conformational changes that interfere with the binding of bacterial adhesins (fimbriae) to receptors on eukaryotic cells. At subinhibitory concentrations, the macrolide clarithromycin inhibits the expression of adhesins on bacterial cell surfaces. The addition of 5 and 10 µg/ml of Met I to 1/8, 1/16 and 1/32 MIC of clarithromycin potentiated the inhibition of Staphylococcus aureus adhesiveness to human mucosal cells in comparison with the antibiotic alone. This finding opens up a new possibility of interfering with bacterial adhesiveness and its resulting pathogenicity not only by using antibiotics but also by means of their combination with agents devoid of antibacterial activity.
Treatment of Febrile Neutropenia with Cefepime Monotherapy
Authors: Jándula Barbara M. , Martino Rodrigo , Gurgi Mercedes , Manteıga Rosa , Sierra Jorge
Published: April 2003

Background and Objective: The empirical administration of a broad-spectrum β-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. Methods: One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Results: Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Interpretation and Conclusions: Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be at higher risk for failure. However, with appropriate therapeutic changes the risk of dying from a bacterial infection is very low.
Sclerosing Encapsulating Peritonitis: Regional Changes of Peritoneum
Authors: Okada Kazuyoshi , Onishi Yoshihiko , Oinuma Toshinori , Nagura Yuji , Soma Masayoshi , Saito Satoshi , Kanmatsuse Katsuo , Takahashi Susumu
Published: April 2003

Sclerosing encapsulating peritonitis (SEP) is characterized by the diffuse appearance of marked sclerotic thickening of the peritoneal membrane. We experienced a case with SEP accompanied by regional changes of peritoneum. A 37-year-old woman with end-stage renal failure was started on continuous ambulatory peritoneal dialysis in 1985 and was transferred to hemodialysis in 1997. She was admitted because of ileus in 1998 with SEP and died of septicemia. The diagnosis of SEP was confirmed via the autopsy. The root of the mesentery was retracted and shortened. Since the peritoneal change was marked in the regions with free margin of mesentery and was less apparent in the regions not adhered to mesentery, it is indicated that mechanical stress also contributes to the occurrence of SEP. Since calcification and ossification were only seen in a free margin of small bowel from mesentery, it is suggested that there is a close relationship between calcification and ossification. Since fibrosis invaded into the muscle layer, dysfunction of bowel movement as well as bowel obstruction contributed to the appearance of ileus. It is suggested that mechanical stress by the root of mesentery which is retracted and shortened also contributes to the appearance of SEP.
Segmental Neurofibromatosis
Authors: Schultz Erwin S. , Kaufmann Dieter , Tinschert Sigrid , Schell Hermann , von den Driesch Peter , Schuler Gerold
Published: April 2003

Segmental neurofibromatosis is characterised by a limited, segmental distribution of cutaneous neurofibromatosis type 1 (NF1) lesions. It has been suggested that segmental NF results from a postzygotic NF1 gene mutation, and, recently, this hypothesis has been proven in a patient with regionally distributed café-au-lait (CAL) spots and freckles by demonstrating an NF1 microdeletion restricted to fibroblasts cultured from CAL spots. We describe here a patient with segmental NF in which we could not demonstrate any NF1 gene mutation in fibroblasts cultured from neurofibromas by use of the protein truncation test, enzymatic mutation detection and fluorescence in situ hybridisation. These data are in line with the concept that NF1 mutations in Schwann cells, but not in fibroblasts, correlate with neurofibroma formation.
A Fetus with Trisomy 9p and Trisomy 10p Originating from Unbalanced Segregation of a Maternal Complex Chromosome Rearrangement t(4;10;9)
Authors: Hengstschläger Markus , Bettelheim Dieter , Repa Christa , Lang Susanna , Deutinger Josef , Bernaschek Gerhard
Published: April 2003

Complex chromosome rearrangements are only rarely seen in constitutional karyotypes. A case of prenatally detected trisomy 9p with trisomy 10p originating from adjacent segregation of a maternal complex chromosome rearrangement is reported. Ultrasound examination at 18 weeks of gestation showed cleft lip palate, club feet, structural anomalies of the cerebellum and cystic kidneys. Cytogenetic analysis of amnion cells revealed a female fetus with 47,XX,+der(9). FISH analyses together with parental karyotyping demonstrated the fetal additional chromosome to originate from malsegregation of a maternal complex chromosomal rearrangement. The mother is carrier of a balanced translocation t(4;10;9) (q12; p11;q13). Postmortem examination of the fetus showed nose anomalies, cleft lip palate, low set ears, club feet, lung anomalies, cystic kidney and aplasia of the uterus. Reporting of such rare cases is important in order to enable this information to be used for genetic counselling in similar situations.
Gonadotrophin-Independent Puberty in a Boy with a β-HCG-Secreting Brain Tumour
Authors: Marx M. , Beck J.D. , Grabenbauer G.G. , Fahlbusch R.
Published: April 2003

We report on a short-statured boy in whom therapy with recombinant human growth hormone was initiated at the age of 9.7 years for assumed idiopathic growth hormone deficiency. On recombinant human growth hormone, height improved from –1.9 (standard deviation score) to –0.9 within 1 year, and the patient entered puberty spontaneously at 10.7 years. At 11.6 years he showed low morning cortisol and thyroxine levels, but was otherwise well. He showed an inconspicuous growth, and puberty progressed adequately until the age of 13.4 years, when he developed signs of an increased intracranial pressure, and a suprasellar choriocarcinoma was diagnosed. This case confirms the fact that beta chorionic gonadotrophin secreting tumours will not be diagnosed by the characteristic clinical manifestation of gonadotrophin-independent puberty if they occur at a time when normal puberty is expected. Particularly, it raises the question of how often the CNS should be re-evaluated by magnetic resonance imaging in children with growth hormone deficiency and normal initial neuroradiological imaging, when they develop additional hormonal deficiencies but no other clinical symptoms of an intracranial process.
Identification of Monoclonal Insulin Autoantibodies in Insulin Autoimmune Syndrome Associated with HLA-DRB1*0401
Authors: Murakami Masami , Mizuide Masafumi , Kashima Koji , Kojima Akira , Tomioka Shin-ichi , Kohama Tomoko , Araki Osamu , Ogiwara Takayuki , Mizuma Haruo , Mori Masatomo
Published: April 2003

We have characterized HLA and insulin autoantibodies in a Japanese female patient with insulin autoimmune syndrome. Serological HLA typing demonstrated the patient had HLA-DR4, and DNA typing showed she had HLA-DRB1*0401 which has not been reported in patients with insulin autoimmune syndrome in Japan. A single binding affinity of insulin autoantibodies was demonstrated by Scatchard analysis and immunoglobulin class of insulin autoantibodies was exclusively IgG-ĸ. HLA-DRB1*0406 is strikingly associated with patients with insulin autoimmune syndrome who have polyclonal insulin autoantibodies. The present report demonstrated the first Japanese patient with insulin autoimmune syndrome carrying HLA-DRB1*0401 who was revealed to have monoclonal insulin autoantibodies. The present results indicate that HLA molecules are the major determinants of polyclonal insulin autoantibodies and monoclonal insulin autoantibodies in insulin autoimmune syndrome.
Critical Ages and Stages of Puberty in the Accumulation of Spinal and Femoral Bone Mass: The Validity of Bone Mass Measurements
Authors: Baroncelli Giampiero Igli , Saggese Giuseppe
Published: April 2003

In growing children, lumbar and femoral areal bone mineral density (aBMD), as measured by dual-energy X-ray absorptiometry (DXA), is influenced by skeletal growth and bone size. Correction of lumbar bone mineral density (BMD) for bone volume (volumetric BMD [vBMD]), by the use of mathematical extrapolations, reduces the confounding effect of bone size, but vBMD remains dependent on age and bone size during growth. Femoral (neck and mid-shaft) vBMD, assessed by DXA, is independent of age prior to puberty, but a slight increase occurs in late puberty and after menarche. Femoral (mid-shaft) cortical bone density and radial cortical and trabecular bone densities, assessed by quantitative computed tomography (QCT), show no peak during childhood or adolescence. Bone strength index, calculated by peripheral QCT, increases with age and correlates with handgrip strength, bone cross-sectional area and cortical area. Puberty is one of the main factors that influences lumbar bone mineral content and aBMD accumulation, but a high incidence of fractures occurs during this period of life, which may be associated with a reduced aBMD.
Assessment of Bone Architecture with Ultrasonometry: Experimental and Clinical Experience
Authors: Cadossi Ruggero , de Terlizzi Francesca , Canè Valerio , Fini Milena , Wüster Christian
Published: April 2003

Over the last decade, ultrasound technology has been introduced as a method of analysing bone tissue in clinical practice, and several studies have compared various ultrasound devices with dual-energy X-ray absorptiometry (DXA). Unlike DXA, the ultrasound technique is not limited to the measurement of bone density – it also has the potential to provide information on the mechanical and architectural characteristics of bone. The first generation of ultrasound devices used the speed of sound and attenuation of the ultrasound signal to obtain information on bone mineral content. Second generation ultrasound devices, which analyse the ultrasound signal received, permit the study of bone structure and elasticity, in addition to its mineral content, in both experimental studies and clinical practice. This is accomplished by signal processing analysis, the study of backscattering and the application of Biot’s theory. This approach to the study of bone tissue represents the future for the development of ultrasound technology for use in clinical practice.