bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Myocardial β-Adrenergic Receptor Function in Adult and Neonatal Rabbits
Authors: Sun Lena S.
Published: April 2003

β-Adrenergic receptor (βAR) desensitization is the decrease in response following sustained agonist stimulation by catecholamines. While developmental changes in βAR response have been well documented in the mammalian heart, much less is known regarding the regulation of βAR function in immature hearts. The purpose of the present study was to determine whether there are developmental differences in myocardial βAR desensitization. We used an isolated heart preparation to examine the βAR-mediated inotropic response before and after sustained exposure to 1 μM isoproterenol in adult and neonatal rabbits. We also assayed the adenylyl cyclase activity and performed radioligand-binding studies to determine βAR characteristics in adult and neonatal ventricular tissues with and without exposure to isoproterenol. Both adult and neonatal rabbit hearts showed a concentration-dependent increase in systolic function, namely, isovolumic left ventricular developed pressure (LVDP) and maximal positive dP/dt of LVDP (dP/dtmax) in response to isoproterenol. Adults, however, showed a significantly greater response than neonates. After sustained exposure to isoproterenol, the subsequent βAR-mediated responses in LVDP and dP/dtmax were significantly attenuated in adults, but much less so in neonates. The adenylyl cyclase activity in response to isoproterenol was significantly different between adult, but comparable in neonatal tissues both exposed or not to isoproterenol. The total βAR density was higher in neonatal than in adult tissues without isoproterenol exposure, but there was no significant change in βAR density in either group following isoproterenol exposure. In addition, isoproterenol exposure increased the amount of the inhibitory G protein in adult, but not neonatal tissues. Our results suggest that there were developmental differences in myocardial βAR functional responses in βAR desensitization.
Brainstem Auditory Evoked Response Recorded Using Maximum Length Sequences in Term Neonates
Authors: Jiang Ze D. , Brosi Dorothea M. , Wilkinson Andrew R.
Published: April 2003

Brainstem auditory evoked response (BAER) was studied in term neonates using maximum length sequences (MLS), which allows presentation of acoustic stimuli at much higher rate than possible with conventional averaging technique. The response waveforms, especially for waves III and V, were well defined at the click rates of 91–455/s. Wave latencies and interpeak intervals at various click rates were all significantly longer and wave V amplitude was smaller in the neonates than in the adults. As click rate was increased, wave latencies increased and amplitudes progressively reduced. The slopes of wave latency-rate functions were progressively steeper for the later waves. The slopes of both III–V and I–V interval-rate functions were significantly steeper in the neonates than in the adults, indicating greater rate-dependent changes in the central components of the neonatal MLS BAER. These rate-dependent changes in the neonatal MLS BAER are generally similar to those in neonatal conventional BAER, although there are some differences. The results indicate that the neonatal brainstem can process rapid acoustic stimulation up to 455/s, although this ability remains immature.
Early (4–7 Days of Age) Dexamethasone Therapy for Prevention of Chronic Lung Disease in Preterm Infants
Authors: Tsukahara Hirokazu , Watanabe Yasuhiro , Yasutomi Motoko , Kobata Ritsuyo , Tamura Satoshi , Kimura Kouki , Hiraoka Masahiro , Mayumi Mitsufumi
Published: April 2003

We conducted a comparative study to evaluate whether early (4–7 days of age) low-dose dexamethasone (DEX) therapy in preterm infants with surfactant-pretreated respiratory distress syndrome (RDS) would facilitate extubation and improve the clinical outcome. Twenty-six preterm infants with surfactant-pretreated RDS who were oxygen- and ventilator-dependent at 4 days of postnatal age were enrolled. Twelve infants were in the historical comparison group, and 14 infants were assigned to receive DEX 0.125 mg/kg i.v., every 12 h, for a total of 6 doses. At study entry, the two groups had a comparable clinical status. DEX therapy significantly facilitated weaning from mechanical ventilation (median interval, 6 vs. 24 days, p < 0.005) and shortened duration of oxygen supplementation (9 vs. 28 days, p < 0.05) as compared with the historical comparison group. At 28 days of age, the occurrence of chronic lung disease (CLD) was significantly lower (1/14 vs. 6/12, p < 0.05) and there was a significant decrease in the incidence of ventilator dependence (0/14 vs. 5/12, p < 0.05) in the DEX group. DEX therapy did not influence the incidence of significant complications such as infection, periventricular leukomalacia or retinopathy of prematurity. We conclude that in a selected high-risk group of preterm infants, early low-dose DEX treatment results in improvement in pulmonary outcome without significant side effects.
Hypoxia-Induced Release of Peptide Growth Factors from Neonatal Porcine Pulmonary Artery Smooth Muscle Cells
Authors: Ambalavanan Namasivayam , Bulger Arlene , Philips III Joseph B.
Published: April 2003

Peptide growth factors are involved in hypoxia-mediated neonatal pulmonary vascular remodeling. The role of hypoxia in the release of selected peptide growth factors from neonatal porcine pulmonary artery smooth muscle cells (PASMC) was examined. PASMC were exposed to different oxygen tensions and the cells were counted electronically and the conditioned media analyzed for basic fibroblast growth factor (bFGF), endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). The effect of conditioned media on PASMC proliferation was also measured. Hypoxia (1% oxygen) and hypoxia-conditioned media increased PASMC numbers, and this mitogenic effect was abolished by anti-bFGF, but not by anti-PDGF or anti-VEGF. Hpyoxia increased bFGF and VEGF release but not PDGF or ET-1. This suggests that PASMC-derived bFGF and VEGF may participate in hypoxic neonatal pulmonary vascular remodeling.
Hereditary Cancer and Developmental Abnormalities
Authors: Ben-Yosef Tamar , Benvenisty Nissim
Published: April 2003

About 1% of all cancers are hereditary, caused by germline mutations in specific cancer-related genes. More than 25 different hereditary cancer syndromes are known, most of them involving mutations in tumor suppressor genes. These genes, which are related to cellular proliferation, might also be involved in differentiation. Hence, the phenotype of hereditary cancer syndromes might include developmental abnormalities, in addition to cancer predisposition. The information summarized here indicates that developmental phenotypes appear in both human patients and mouse models of the various hereditary cancer syndromes. These developmental abnormalities, which involve a variety of tissues and organs, usually lead to embryonic malformation that prevents the birth of viable homozygous offspring, but can also be detected in heterozygotes. In some of the syndromes a correlation exists between tumor types and developmentally affected tissues. Comparison of mice and human phenotypes from both the cancer and the developmental aspects indicates that many of the mouse models mimic the human syndromes. Our analysis indicates that most tumor suppressor genes participate not only in the regulation of cell proliferation, but also in differentiation and embryogenesis.
Changes in Body Composition during the Initial Hours of Life in Breast-Fed Healthy Term Newborns
Authors: Rodríguez Gerardo , Ventura Purificación , Samper Maria Pilar , Moreno Luis , Sarría Antonio , Pérez-González José M.
Published: April 2003

Newborns usually lose 5–10% of their initial weight during the first 4 days of life. Our aim, using bioelectrical impedance (BI), was to study the body composition of healthy term newborns and the nature of the changes which accompany this physiological weight loss. Forty-three healthy term newborns, all with adequate weight for their gestational age, were studied during the first 3 days of life. Weight and BI were taken on the 1st, 2nd, and 3rd days of life, always at the same time of the day. Total body water (TBW), percentage of total body mass hydration (%TBW), and amount of body solids were calculated. Average weight at birth was 3,297 ± 381 g, length 50.04 ± 1.75 cm, and gestational age 39.9 ± 0.84 weeks. Weight, TBW, and body solids decreased progressively during the first 3 days of life (p < 0.000). By day 3, weight loss represented 5.67 ± 1.98% of birth weight, but %TBW increased slightly (1.72%; p < 0.000). These results suggest that, during physiological weight loss, body composition modifications are produced in the term newborn by a decrease in TBW and loss of body solids. The level of body hydration increases slightly, since the loss of body solids is greater than the loss of TBW. The use of BI can help us in the study of body composition and the short- and/or long-term changes produced therein, in the newborn.
Effect of Prenatal Glucocorticoid on Fetal Lung Ultrastructural Maturation in hyt/hyt Mice with Primary Hypothyroidism
Authors: Ansari Mohammed A. , de Mello Daphne E. , Devaskar Uday P.
Published: April 2003

Glucocorticoids (GC) and thyroid hormones (TH) accelerate fetal lung maturation. Though GC are used clinically, the mechanisms of GC-induced fetal lung maturity remain unclear. Prenatal GC increase fetal TH activity in humans and in animals. Thus, it is possible that increased fetal TH activity after prenatal GC plays a role in accelerating fetal lung maturation. However, this hypothesis has remained untested due to the lack of a suitable animal model. In the hyt/hyt mouse primary hypothyroidism occurs due to a point mutation in the beta subunit of the thyroid-stimulating hormone receptor of the thyroid gland, and it is transmitted in an autosomal recessive manner. We studied the effect of maternal betamethasone on fetal lung ultrastructure in hyt/hyt (hypothyroid) and Balb-c (euthyroid) mice. Hypothyroid mice were made euthyroid by T3 supplementation and mated to carry hypothyroid pups. Vehicle (n = 6) or betamethasone (n = 6) was injected intraperitoneally twice daily into the doe on days 16 and 17 of gestation. Fetal lungs on 18 days of gestation were subjected to ultrastructural morphometric analysis. The number of lamellar bodies per type II cell increased after betamethasone in Balb-c (2.10 ± 0.31 vs. 3.43 ± 0.37) and hyt/hyt (0.77 ±0.28 vs. 3.85 ± 0.26) mice. The alveolar-to-parenchymal ratio was less in the vehicle-treated hyt/hyt (0.082 ± 0.024) as compared with the vehicle-treated Balb-c (0.30 ± 0.05) mice, while prenatal betamethasone increased the alveolar-to-parenchymal ratio in the hyt/hyt (0.227 ± 0.034) but not in the Balb-c (0.26 ± 0.04) mice. The glycogen-to-nucleus ratio was higher in betamethasone-treated hyt/hyt mice (1.46 ± 0.20) when compared to vehicle-treated hyt/hyt (0.89 ± 0.14) or Balb-c (1.01 ± 0.17) or betamethasone-treated Balb-c (0.81 ± 0.13) mice. Though tubular myelin was readily apparent in the airspace lumen of betamethasone-treated Balb-c mice, it was absent in betamethasone-treated hyt/hyt fetal lungs. We conclude that fetal thyroid plays an important role in accelerating some aspects of fetal lung ultrastructural maturation from GC stimulation.
Influence of Mild Hypothermia after Hypoxia-Ischemia on the Pharmacokinetics of Gentamicin in Newborn Pigs
Authors: Šatas Saulius , Hoem Nils Ove , Melby Kjetil , Porter Helen , Lindgren Carl G. , Whitelaw Andrew , Thoresen Marianne
Published: April 2003

The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39°C) for 72 h (n = 8) or mild hypothermia (35°C) for 24 h followed by normothermia (39°C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39°C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.
Effect of Cisapride on Acid Gastro-Oesophageal Reflux during Treatment with Caffeine
Authors: Kentrup H. , Baisch H.-J. , Kusenbach G. , Heimann G. , Skopnik H.
Published: April 2003

About 50% of preterm infants and neonates receiving methylxanthines for respiratory stimulation will develop a pathological gastro-oesophageal reflux (GOR) pattern. In the face of potential GOR-related complications the effect of a concomitant treatment with a prokinetic agent, such as cisapride, should be evaluated. In this study 32 formerly preterm infants were studied simultaneously by 24-hour oesophageal pH monitoring and cardio-respirogram before the presumed end of caffeine treatment. In 14 of these infants a reflux index (RI; percentage of recording time) of more than 4% could be detected (pH <4). Ten of them were treated orally with cisapride (0.2 mg/kg t.i.d.). Data of pH monitoring, cardio-respirogram and caffeine serum concentrations were obtained before and 5 days after introducing cisapride. The RI and the frequency of GOR decreased significantly with cisapride. The steady-state serum concentrations of caffeine were not influenced by cisapride and the extent of periodic breathing remained unchanged. In conclusion, cisapride has a positive influence on GOR parameters during caffeine treatment without impairing the oral bioavailability or therapeutic effect of caffeine.
Nonnutritive Sucking during Heelstick Procedures Decreases Behavioral Distress in the Newborn Infant
Authors: Corbo M.G. , Mansi G. , Stagni A. , Romano A. , van den Heuvel J. , Capasso L. , Raffio T. , Zoccali S. , Paludetto R.
Published: April 2003

We investigated if nonnutritive sucking (NNS) during heelstick procedures alleviates behavioral distress in neonates. In our NICU, 26 neonates without severe complications (mean Minde score 0.8, range 0–3), undergoing heelstick procedures at least twice a day, in the first 2 weeks of life, were enrolled in the trial (mean gestational age 33.9 weeks, range 26–39 weeks, mean birth weight 1,988.5 g, range 1,200–4,010 g, mean Apgar score at the first minute 6.7, range 4–10, at the fifth minute 8.5, range 6–10). Two heelpricks were performed in each neonate with NNS randomly assigned. Behavioral states, transcutaneous oxygen tension (TcPO2), heart rate, and respiratory rate were monitored before, during and after the heelstick procedures. Heelstick procedures lasted for a mean of 109 s (range 50–230 s) with NNS, and a mean of 128.8 s (range 20–420 s) without NNS. Compared with baseline, heart rate and behavioral distress increased and respiratory rate decreased during heelstick and after heelstick. Oxygen tension did not change. Nonnutritive sucking had no effect on respiratory rate or transcutaneous oxygen tension, but reduced the time of crying and the heart rate increase during the procedure. In conclusion, NNS can be recommended to reduce distress in newborns undergoing invasive routine procedures. Further studies are needed to evaluate the effects of NNS on respiratory rate and blood gas levels.
The Effect of Cold Stimulation to the Face on the Metabolic Rate of the Febrile Piglet
Authors: Voss L.J. , Galland B.C. , Bolton D.P.G. , Taylor B.J.
Published: April 2003

Sudden infant death syndrome has been associated with winter climates, infection, and overwrapping of babies. The hypothesis has been tested in this laboratory that two different causes of increased metabolic rate, high core temperature (via the van’t Hoff or ‘Q10’ effect) and face-cooling, might synergistically induce hyperthermia. This proved not to be the case. We now report on a ‘febrile’ state adding Salmonella abortus equi pyrogens. The combination of face-cooling and pyrogen administration to 14 already hot piglets produced an increase in oxygen consumption of 47% in 6 of the animals (19% overall). Face-cooling alone caused a 6.5% fall in oxygen consumption, and injection of pyrogens alone had no effect on oxygen consumption. We conclude that there may be a danger of life-threatening hyperthermia in the combination of a cold face and febrile state.
Bioactive Transforming Growth Factor-Beta in the Lungs of Extremely Low Birthweight Neonates Predicts the Need for Home Oxygen Supplementation
Authors: Lecart C. , Cayabyab R. , Buckley S. , Morrison J. , Kwong K.Y. , Warburton D. , Ramanathan R. , Jones C.A. , Minoo P.
Published: April 2003

Transforming growth factor-β (TGF-β) is a peptide implicated in tissue injury and repair but its role in the premature human lung remains unclear. In the present study, we used a TGF-β responsive-promoter-luciferase construct in mink lung epithelial cells to quantify levels of biologically active TGF-β (BA-TGF-β) in the endotracheal aspirate (ETA) fluid from 16 extremely low birthweight neonates [6 M/10 F, mean GA 26 weeks (range 23–30), mean BW 774 g (range 555–1,075)]. ETA fluid was obtained on day 1 and then every 4 days up to 32 days. BA-TGF-β levels were low (92 ± 19 pg/ml) in the first 24 h of life and then increased 5- to 10-fold with peak BA-TGF-β levels (400 ± 50 pg/ml) on day 20–25. BA-TGF-β levels were higher in male than female infants (p = 0.0056). Prenatal steroids decreased significantly the amount of BA-TGF-β recovered. High initial levels of BA-TGF-β persisted over time and were predictive of the need for oxygen therapy at home. We conclude that abundant BA- TGF-β is present in the lungs of preterm infants and speculate that it may be involved in inflammatory and repair processes encountered in acute and chronic lung disease.
Surfactant Treatment Effects on Lung Structure and Type II Cells of Preterm Ventilated Lambs
Authors: Pinkerton Kent E. , Ikegami Machiko , Dillard Lisa M. , Jobe Alan H.
Published: April 2003

We evaluated surfactant treatment effects on lung morphology and alveolar type II cells of preterm ventilated lambs. Lambs were ventilated for 10 h following treatment of the right lung with natural surfactant. Lung parenchyma from the surfactant-treated right and the untreated left lung was compared morphometrically. Mechanical ventilation without surfactant resulted in distention of alveolar ducts accompanied by shallowing and loss of well-defined alveoli without disruption of collagen or elastin fibers. Surfactant treatment almost completely prevented these changes. The percent of normal parenchyma was 82 ± 7% in surfactant-treated lobes and 26 ± 5% in the nontreated lobes (p < 0.05). Type II cells became flatter in lungs ventilated without surfactant, and cell shape was preserved by surfactant treatment. The volume densities of lamellar bodies and multivesicular bodies in alveolar type II cells were not changed by surfactant treatment. With or without surfactant treatment, mechanical ventilation was associated with a shift in lamellar body distribution to a smaller size and a decrease in glycogen content of type II cells. Surfactant treatment of the preterm lung prevents alveolar distortion and atelectasis, but does not result in changes in subcellular organelles in immature type II cells.
Adhesion Molecules in Early Neonatal Life
Authors: Malamitsi-Puchner Ariadne , Tziotis John , Mastorakos George , Protonotariou Efthimia , Creatsas George
Published: April 2003

This study investigated whether serum levels of the adhesion molecules VCAM-1, PECAM-1 and L-selectin, all of which have been implicated in normal immune function, change soon after birth. Moreover, the dependence of serum levels of the above-mentioned adhesion molecules on sex and mode of delivery was studied. In healthy neonates, serum levels of L-selectin, PECAM-1, and VCAM-1 do not change during early neonatal life. Thus, significant differences in their serum concentrations soon after birth might imply inflammatory processes or deranged endothelial homeostasis, serving as possible diagnostic markers.
Urinary Nitric Oxide in Newborns with Infections
Authors: Ergenekon Ebru , Gücüyener Kıvılcım , Erbaş Deniz , Koç Esin , Özturk Güler , Atalay Yıldız
Published: April 2003

Background: Neonatal sepsis is a major problem in newborn nurseries because of the difficulty in early diagnosis and because of the high morbidity and mortality. The objective of the present study was to investigate whether urinary nitric oxide (NO) levels could be useful for the diagnosis of infected newborns. Methods: Newborns with suspected infection according to previously defined criteria between ages of 1–7 days and 8–30 days were included as the study groups (p) to be compared with age-matched healthy controls (c). Urine NO levels were assayed by Sievers NOA based on chemiluminescence and expressed as corrected for urine creatinine. Results: 20 newborns with suspected infection at 1–7 days of age (group 1p) were compared with 45 healthy age-matched newborns (group 1c). 16 newborns with suspected infection at 8–30 days of age (group 2p) were compared with 15 healthy age-matched newborns (group 2c). The groups were similar with regard to birth weight and gestational age; however, the urinary NO levels in newborns with suspected infection at 1–7 days of age (80.25 ± 60.68 μmol/mg creatinine) were higher than in healthy newborns (25.45 ± 19.35 μmol/mg creatinine). Similarly, newborns with suspected infection at 8–30 days of age had higher urinary NO levels (81.78 ± 40.43 μmol/mg creatinine) than age-matched controls (36.99 ± 24.58 μmol/mg creatinine; p < 0.05). The sensitivity of urinary NO levels to detect infection was 50% in both age groups, and the specificity was 95% for 1–7 days of age and 93% for 8–30 days of age. Groups 1p and 2p were similar with regard to NO production. Altogether 12 patients had culture-proven sepsis, 11 patients had clinical sepsis, and 13 patients had other infections. The NO levels were similar in patients with culture-proven and clinical sepsis and higher than in patients with other infections. No difference was observed among NO levels of patients with gram-positive and gram-negative sepsis. Conclusions: Urinary NO levels which are quick and easy to measure are higher in infected newborns as compared with controls, and although the specificity is good, the sensitivity of the test is low, necessitating the use of another marker in addition to NO.
Effects of Anti-CD18 Monoclonal Antibody, R15.7, on the Cardiopulmonary Manifestations of Group B Streptococcal Sepsis in Piglets
Authors: Bandel Jack W. , Goldberg Ronald N. , Suguihara Cleide , Nagoshi Ren , Martinez Octavio , Rothlein Robert , Ruiz Phillip , Bancalari Eduardo
Published: April 2003

We hypothesized that anti-CD18 monoclonal antibody, R15.7, a murine IgG1 antibody which blocks leukocyte-endothelial cell adherence, might ameliorate the cardiopulmonary manifestations of sepsis secondary to group B streptococci (GBS). Twenty-six anesthetized, mechanically ventilated newborn piglets received a continuous infusion of GBS (7.5 × 109 cfu/kg/min) and were randomly assigned to a treatment group receiving R15.7 (1 mg/kg i.v.) 15 min prior to GBS infusion or to a control group. Cardiopulmonary measurements, arterial blood gases and peripheral blood leukocytes were obtained over 120 min of R15.7 infusion. GBS infusion caused significant increases in pulmonary artery and systemic arterial blood (Psa) pressures, pulmonary vascular (PVR) and systemic vascular (SVR) resistances, and PVR/SVR ratio with decreases in cardiac output and stroke volume. R15.7-treated piglets maintained significantly higher Psa (p < 0.003), dynamic lung compliance (p < 0.04), PaO2 and pH (p < 0.05), and lower total lung resistance (p < 0.01) and PaCO2 (p < 0.04). A longer median survival time was observed in the treatment group (p < 0.01). These data suggest that administration of a CD18-blocking agent prolongs survival in a young animal model of GBS sepsis, possibly secondary to improved tissue perfusion, lung mechanics and acid-base status.
Plasma Carbon Monoxide Levels inTerm Newborn Infants with Sepsis
Authors: Shi Yuan , Pan Feng , Li Huaqiang , Pan Jie , Qin Shiwen , Jiang Dongbo , Shen Chikao
Published: April 2003

Carbon monoxide (CO) has been implicated as a new endogenously produced mediator similar to nitric oxide (NO). CO was measured in plasma samples from 7 term newborn infants with sepsis and from 30 healthy neonates. Plasma CO levels were significantly higher in the group with sepsis at the time of admission to the neonatal intensive care unit than in the healthy controls (p < 0.05). Moreover, the elevated plasma CO levels were significantly related to increased NO production, as indicated by plasma nitrite/nitrate levels (p < 0.05). The present study suggests that, in addition to NO, CO might be another important mediator taking part in the pathogenesis of neonatal sepsis.
Biphasic Response of the Ductus arteriosus to Combined Administration of Indomethacin and L-NAME in Fetal Rats
Authors: Takizawa Tatsuya , Horikoshi Emiko , Kamata Akira
Published: April 2003

We studied the combined effects of indomethacin, a cyclooxygenase inhibitor, and NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on the patency of the ductus arteriosus (DA) in fetal rats. Pregnant rats were administered indomethacin (3 mg/kg) orally 3 h before cesarean section, and then L-NAME (5 and 50 mg/kg), D-NAME, an enantiomer of L-NAME (50 mg/kg), or methylene blue, a soluble guanylate cyclase inhibitor (100 mg/kg), was injected intraperitoneally at various times before the cesarean section. Using rapid freezing and shaving methods, the calibers of the DA were measured. Compared with the indomethacin alone group, L-NAME caused a rapid and marked increase in the DA caliber 0.5 h after injection in fetal rats in which the DA was constricted by treatment with indomethacin. Subsequently, the transient ductal dilatation was completely reversed by 3 h after the L-NAME injection. Methylene blue also caused a biphasic response, but D-NAME did not affect the DA caliber. We conclude that the inhibition of both cyclooxygenase (indomethacin) and NO synthase (L-NAME) or NO action (methylene blue) causes a biphasic effect on the DA caliber in fetal rats.
Cytogenetics of Hodgkin’s disease
Authors: Atkin N.B.
Published: April 2003

Cytogenetic studies over the past 35 years have made a major contribution towards the understanding of the nature of Hodgkin’s disease by demonstrating unequivocally the consistent presence of a clonal population of cells that have the cardinal features of malignancy e.g. more or less gross aneuploidy, frequently with complex chromosomal changes and showing considerable variation from case to case, thus comparable to the findings in carcinomas and other solid cancers. The mode is frequently in the triploid-tetraploid region, as we found in 17 of 27 cases studied in this laboratory by Feulgen microspectrophotometry, compared to only 10 cases with neardiploid modes. It is disappointing that no specific change, such as a translocation that could give a clue to the chromosomal location of a gene or genes involved in the etiology of Hodgkin’s disease, has yet been found. Nevertheless it is clear that a number of nonrandom changes, including several that are also common in other malignancies including the non-Hodgkin’s lymphomas, are frequently present, e.g., deletions of 1p, 6q, and 7q. Interestingly, deletions of 4q, with loss of 4q25→q27, that have also been reported may show some specificity for Hodgkin’s disease.
An analysis of meiotic pairing in trisomy 21 oocytes using fluorescent in situ hybridization
Authors: Cheng E.Y. , Chen Y.-J. , Bonnet G. , Gartler S.M.
Published: April 2003

We report the use of chromosome 21-specific painting probes to analyze early stages of oogenesis in nine trisomy 21 fetuses. The proportion of cells in zygotene and pachytene in the trisomic ovaries ranged from 8 to 70% with a mean of 42% ± 19 while the comparable values of euploid specimens ranged from 34 to 90% with a mean of 65% ± 19. The low proportion of pairing cells may be the basis for the ovarian dysgenesis observed in some trisomy infants. Five percent of trisomic pachytene cells exhibited complete asynapsis which is an order of magnitude higher than that observed in euploid cells. A large fraction of the asynaptic cells were atretic which is consistent with the hypothesis of meiotic pairing as a signal for atresia. In addition, the asynaptic cells exhibited asynapsis of chromosomes other than 21, which we interpret as an interchromosomal effect of trisomy 21.
X-Chromosome inactivation: a repeat hypothesis
Authors: Lyon M.F.
Published: April 2003

Recent work has shown that X-chromosome inactivation is brought about by Xist mRNA, which coats the inactive X-chromosome. This paper presents a hypothesis on the function of this RNA. It is suggested that interspersed repetitive elements of the LINE type, in which the X-chromosome is particularly rich, act as booster elements to promote the spread of Xist mRNA. Contact with this RNA causes the LINE elements to be sensed as repeated elements by the cell’s system for repeat-induced gene silencing. This leads to the silencing of these elements and the intervening unique sequences by their conversion to heterochromatin.
Non-random X chromosome inactivation in mammalian cells
Authors: Migeon B.R.
Published: April 2003

A salient feature of mammalian X dosage compensation is that X-inactivation occurs without regard to the parental origin of either active or inactive X. However, there are variations on the theme of random inactivation, namely paternal X inactivation in marsupials and in placental tissues of some mammals. Whether inactivation is random or paternal seems to depend on the time when this developmental program is initiated. As deletions of the X inactivation center (XIC/Xic) and/or the X inactive specific transcript (XIST/Xist) gene result in failure of cis X-inactivation, mutations in genes from this region might lead to preferential inactivation of one X chromosome or the other. The Xce locus in the murine Xic is considered a prototype for this model. Recent studies suggest that choice involves maintaining the activity of one X, while the other(s) by default is programmed to become inactive. Also, choice resides within the XIC, so that mutations elsewhere, although perhaps able to interfere with cis inactivation, are not likely to affect the X chromosome from only one parent. Mutations affecting the choice of active X will be more difficult to detect in humans than in inbred laboratory mice because of the greater allelic differences between maternal and paternal X chromosomes; some of these differences predispose to growth competition between the mosaic cell populations. I suggest that the skewing of inactivation patterns observed in human females most often occurs after random X inactivation, and is due mainly to cell selection favoring alleles that provide a relative growth advantage.
Spermatogenesis in common shrews, Sorex araneus, from a hybrid zone with extensive Robertsonian polymorphism
Authors: Narain Y. , Fredga K.
Published: April 2003

The analysis of the fertility of hybrid and non-hybrid individuals from a chromosomal contact zone gives us the possibility of studying the role of chromosomes in speciation processes. In this study, homozygous, “simple” and “complex” Robertsonian heterozygous male common shrews (Sorex araneus) from the Abisko-Sidensjö chromosomal hybrid zone in Sweden were analysed. The degree of germ cell death was estimated, sperm counts were performed and the testis and seminal vesicles weighed in each individual. Chromosome interactions and synapsis at pachytene were examined under the EM. The weight of the testis was significantly different in the three karyotypic groups and “complex” heterozygotes suffered higher germ cell death than homozygotes and “simple” heterozygotes. Interactions between chromosomes at pachytene were rare. Nonhomologous pairing in the centromeric regions of autosomal trivalents (side arms) was common while asynapsed segments were seldom found. Thus, the difference in the reproductive characteristics of the common shrew might be due to genetic factors rather than Robertsonian translocations.
Beta-heterochromatin in mammals: evidence from studies in Microtus agrestis based on the extensive accumulation of L1 and non-L1 retroposons in the heterochromatin
Authors: Neitzel H. , Kalscheuer V. , Henschel S. , Digweed M. , Sperling K.
Published: April 2003

The heterochromatin of Microtus agrestis contains two retroposons, one L1 and one non-L1, which were cloned and analyzed with respect to their structure and genomic organization. These sequences have accumulated in the heterochromatin and exhibit a complex interspersed organization of relatively recent origin. In contrast, the pericentromeric heterochromatin is composed of simple, repetitive, tandemly organized elements. From the underlying sequences, the dinucleotide frequencies, the sequence organization, and its transcriptional activity, the heterochromatin of M. agrestis strongly resembles the β-heterochromatin first described by Heitz and well characterized in Drosophila. This is evidence that this class of heterochromatin, presumably with its own distinct physiological and functional role, is indeed also present in the mammalian genome.
Dispensable and indispensable genes in an ameiotic fish, the Amazon molly Poecilia formosa
Authors: Schlupp I. , Nanda I. , Döbler M. , Lamatsch D.K. , Epplen J.T. , Parzefall J. , Schmid M. , Schartl M.
Published: April 2003

All-female vertebrates are excellent model systems for studying many evolutionary problems. One of these is the Amazon molly. In this review, three aspects of its biology are discussed: (1) An important question is how dispensable genes, such as all male coding genes, evolve in this species. A number of studies found that most of these genes remain remarkably stable and functional. (2) The gynogenetic Amazon mollies have to live in sympatry with males of a gonochoristic species, because sperm are needed to trigger embryogenesis. Yet, Amazon mollies cannot replace their sexual competitors, because this would lead to their own extinction. Studies on the behavior of Amazon mollies and their sperm-donor species indicate that a number of behavior patterns stabilize the mating system by providing Amazon mollies with the copulations they need to reproduce. (3) The age of Amazon mollies has been estimated to be approximately 100,000 years. This is older than predicted by some theoretical models. In Amazon mollies two ways to occasionally incorporate fresh genetic material have evolved. One way is to add one complete set of paternal chromosomes, which, in nature, leads to stable triploid lineages. The second way is the incorporation of minute, centromere-containing microchromosomes. The evolutionary impact of these phenomena, however, is not resolved so far and needs further study.
Structure and function of TSPY, the Y-chromosome gene coding for the “testis-specific protein”
Authors: Vogel T. , Schmidtke J.
Published: April 2003

The TSPY genes are arranged in clusters on the Y chromosome of many mammalian species. TSPY is believed to function in early spermatogenesis and is a candidate for GBY, the putative gonadoblastoma-inducing gene on the Y. The TSPY family forms part of a superfamily, TTSN, with autosomal representatives, highly conserved in mammals and beyond.
Physical mapping of the CA6, ENO1, and SLC2A5 (GLUT5) genes and reassignment of SLC2A5 to 1p36.2
Authors: White P.S. , Jensen S.J. , Rajalingam V. , Stairs D. , Sulman E.P. , Maris J.M. , Biegel J.A. , Wooster R. , Brodeur G.M.
Published: April 2003

Several human malignancies frequently exhibit deletions or rearrangements of the distal short arm of chromosome 1 (1p36), and a number of genetic diseases also map to this region. The carbonic anhydrase (CA6) and α-enolase (ENO1) genes, previously mapped to 1p36, were physically linked in yeast- and P1-artificial chromosome (YAC and PAC) contigs. PACs from the contig were mapped to 1p36.2 by fluorescence in situ hybridization. The ESTs D1S2068, D1S274E, D1S3275, and stSG4370 were also placed in the same contig. The physical map was integrated with the genetic map of chromosome 1 by assignment of genetic markers D1S160, D1S1615, and D1S503 to the contig. Sequencing of the EST clone representing D1S274E indicated that it was derived from the same transcript as D1S2068E and corresponded to the SLC2A5 (GLUT5) gene, previously assigned to 1p31. Reassignment of SLC2A5 to 1p36.2 was confirmed by somatic cell and radiation hybrid mapping panels and was consistent with previous EST mapping data. Sequencing of the EST clone for D1S274E revealed the presence of intronic sequences, suggesting that the clone was derived from an unprocessed message. The presence of unprocessed and/or alternatively spliced EST clones has potential ramifications for EST-based genomic projects. This information should facilitate the mapping of tumor suppressor and genetic disease loci that have been localized to this region.
Chromosome healing of constitutional chromosome deletions studied by microdissection
Authors: Vermeesch J.R. , Falzetti D. , van Buggenhout G. , Fryns J.-P. , Marynen P.
Published: April 2003

Broken chromosomes are highly unstable and are subject to chromosome fusion or loss. As an exception, healing of human chromosomes occurs which can lead to constitutional or acquired terminal chromosome deletion disorders. Both de novo telomere addition at the breakpoint and telomere capture have been implicated as healing mechanisms. We investigated the origin of the novel ends of chromosomes 4p and 5p in a patient with the Wolf-Hirschhorn syndrome and in 4 patients with the Cri-du-Chat syndrome by chromosome microdissection. Our results suggest that de novo telomere synthesis by telomerase is the main mechanism of chromosome healing in constitutional chromosome deletions.
Cloning of a human “epidermal-type” 12-lipoxygenase-related gene and chromosomal localization to 17p13
Authors: Sun D. , Elsea S.H. , Patel P.I. , Funk C.D.
Published: April 2003

A human “epidermal-type” 12-lipoxygenase (e-12LO) pseudogene was cloned using a murine e-12LO cDNA probe. Similar to other lipoxygenase genes, the genomic sequence revealed 14 exons and 13 introns covering 6.7 kb of DNA. cDNA corresponding to this gene was amplified from RNA of human skin and hair follicles by RACE-PCR and displayed 65–80% identity to the three murine 12-lipoxygenase cDNAs. Based on several criteria, humans appear to lack a functional e-12LO gene but instead have acquired an expressed pseudogene. The pseudogene designated ALOX12P2 was localized to chromosome 17p13 by analysis of somatic hybrid DNA panels.
Genomic organization and chromosomal localization of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene: a candidate for 6q-linked retinopathies
Authors: Felbor U. , Gehrig A. , Sauer C.G. , Marquardt A. , Köhler M. , Schmid M. , Weber B.H.F.
Published: April 2003

The interphotoreceptor matrix is a unique extracellular matrix occupying the space between the photoreceptors and the retinal pigment epithelium. Due to its putative function in the maintenance and integrity of the photoreceptor cells, it is conceivable that it is involved in retinal degeneration processes. More recently, a novel gene encoding a 150-kDa interphotoreceptor matrix proteoglycan, designated IMPG1, was cloned and shown to be expressed in both rod and cone photoreceptor cells. To assess this gene in human retinal dystrophies, we have now determined the genomic organization and chro- mosome location of IMPG1. It is composed of 17 exons ranging from 21 to 533 bp, including an alternatively spliced exon 2. Using somatic cell hybrid mapping and FISH analysis, we have assigned the IMPG1 locus to 6q13→q15. As this interval overlaps with the chromosomal loci of several human retinopathies, including autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1), IMPG1 represents an attractive candidate for these 6q-linked disorders.
Homologies between human and dolphin chromosomes detected by heterologous chromosome painting
Authors: Bielec P.E. , Gallagher D.S. , Womack J.E. , Busbee D.L.
Published: April 2003

Human chromosome-specific probes for the entire karyotype were hybridized to metaphase spreads of the Atlantic bottlenose dolphin, Tursiops truncatus, to directly compare the evolutionary conservation of chromosomal segments between these two distantly related species. All human chromosomal paints, except the Y probe, hybridized to Tursiops counterparts, and every dolphin chromosome was painted except for the smallest submetacentric pair. In our analysis, 36 segments of conserved synteny common to the human and dolphin genomes were identified. The distribution of conserved chromosomal segments and the specific rearrangement patterns found between the two genomes are presented and discussed.
Comparative cytogenetic mapping reveals chromosome rearrangements between the X chromosomes of two closely related mammalian species (cattle and goats)
Authors: Piumi F. , Schibler L. , Vaiman D. , Oustry A. , Cribiu E.P.
Published: April 2003

Cytogenetic localization of 24 BACs containing type I (genes and ESTs) and type II (microsatellites) markers were used to construct cytogenetic maps of caprine (CHI) and bovine (BTA) X chromosomes. Comparison of these two maps revealed that the distal region of the goat X long arm (CHI Xq38→q42) was located inside the bovine X chromosome, between PGK1 (BTA Xq25) and DVEPC137 (BTA Xq12). The marker order was globally conserved without any pericentric inversion, as previously postulated in the literature. The caprine centromere was found between DVEPC053 and DVEPC102 (belonging to the same band in the bovine X: BTA Xq41), whereas the bovine centromere was between DVEPC076 and DVEPC132, belonging to the same region of the caprine X chromosome (CHI Xq31→q33). The pseudoautosomal region was situated at the tip of the bovine X long arm and on the tiny short arm of the caprine X chromosome. In the non-pseudoautosomal (NPA) region, the synteny of coding sequences was well conserved between the human species and the two ruminant species, but the gene order was dramatically divergent. It is suggested that the 24 BACs of this study could constitute a new tool to measure phylogenetic distances between different mammalian species by comparing chromosome rearrangements inside the NPA region of the X.
Practicable approaches to targeted comparative mapping of rat chromosome regions: linkage mapping of five genes on rat chromosome 13
Authors: Kato N. , Hyne G. , Rapp J.P. , Lathrop G.M.
Published: April 2003

We demonstrate feasible approaches to comparative mapping between the region near the renin locus on rat chromosome 13 and human chromosome 1q by assigning five additional genes as anchor loci. Base-substitution polymor- phisms were sought in the 3′- and/or 5′-untranslated regions for subsequent development of PCR-amplified markers, which, in turn, could be used for either restriction fragment analysis or allele-specific PCR.
Cloning and mapping of SMARCA5 encoding hSNF2H, a novel human homologue of Drosophila ISWI
Authors: Aihara T. , Miyoshi Y. , Koyama K. , Suzuki M. , Takahashi E. , Monden M. , Nakamura Y.
Published: April 2003

We have isolated a novel cDNA encoding a peptide with 86% sequence homology to hSNF2L protein, a previously isolated human homologue of Drosophila ISWI. This gene, designated SMARCA5, contained an open reading frame of 3,156 nucleotides encoding a 1,052 amino-acid peptide (hSNF2H). As this product also revealed a significant (73%) identity in amino acid sequence to ISWI, a key component of chromatin-remodeling factors in Drosophila, hSNF2H may be another human homologue of this protein and, as such, could be involved in chromatin remodeling in humans. An ATPase domain characteristic of the SWI2/SNF2 family of proteins was highly conserved in ISWI, hSNF2L, and hSNF2H. Northern-blot analysis demonstrated ubiquitous expression of 5.1-kb and 4.1-kb transcripts of the hSNF2H gene. This gene was mapped by FISH to chromosome bands 4q31.1→q31.2.
Cloning and genomic mapping of the mouse matrin 3 gene and its pseudogenes
Authors: Matsushima Y. , Nagabukuro A. , Matsuda Y. , Kitagawa Y.
Published: April 2003

Matrin 3 forms a family of nuclear proteins together with NP220s. Using cDNA sequences encoding rat matrin 3 as a probe, we isolated genomic clones of mouse matrin 3 gene and its two pseudogenes. The genuine mouse matrin 3 gene has an exon covering the N-terminal one third of matrin 3 with a sequence 99% identical to rat matrin 3 cDNA. The gene was localized to Chromosome 18C by in situ hybridization and mapped at 3.6 cM distal to D18Mit117 and 2.2 cM proximal to D18Mit14 on mouse Chromosome 18 by interspecific backcross analysis. One pseudogene has an exon-like sequence covering the N-terminal half of matrin 3 that is interrupted by an unknown sequence. Reverse transcription polymerase chain reaction (RT-PCR) of RNA from mouse liver and brain using unique sequences of the genuine gene and the pseudogene confirmed the expression of only the former. The other pseudogene has a sequence only 80% identical to rat cDNA and is partially deleted and reversed. These pseudogenes were localized to Chromosome 4E2 and 8D2, respectively.
Comparative FISH-mapping of the prion protein gene (PRNP) on cattle, river buffalo, sheep and goat chromosomes
Authors: Iannuzzi L. , Palomba R. , Di Meo G.P. , Perucatti A. , Ferrara L.
Published: April 2003

Comparative FISH-mapping of the prion protein gene (PRNP) was performed on cattle (BTA), river buffalo (BBU), sheep (OAR) and goat (CHI) chromosomes using a PCR-product as a probe and R-banding. PRNP was mapped to BTA13q17, BBU14q15, OAR13q15 and CHI13q15 according to standard nomenclatures. These chromosomes and bands were homoeologous among the four species, confirming the high degree of gene and chromosome banding conservation among bovids. Furthermore, the assignment of PRNP to river buffalo and goat chromosomes allowed us to indirectly assign the bovine syntenic group U11 to specific chromosomes, since it is the first in situ localization on BBU14 and CHI13.
Chromosome identification in human oocytes and polar bodies by spectral karyotyping
Authors: Márquez C. , Cohen J. , Munné S.
Published: April 2003

Sixty unfertilized human oocytes and two fresh polar bodies were karyotyped by spectral karyotyping (SKY). The oocytes were provided by 29 women ranging from 30 to 42 yr of age. The mean hybridization efficiency for oocytes was 95.2% (60/63). Nondisjunction of bivalent chromosomes (13.3%) and predivision of sister chromatids at meiosis I (3.3%) were unequivocally determined by analysis first with SKY and then fluorescence in situ hybridization. Four oocytes (6.7%) were hyperhaploid, six (10.0%) were hypohaploid, one (1.7%) showed balanced predivision, and another (1.7%) was diploid. No specific structural rearrangements were detected. This study demonstrates that the SKY technique can be used successfully as an alternative method of karyotyping second meiotic metaphase chromosomes from human oocytes and polar bodies in appropriate spreads.