bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells
Authors: Singh Jagmohan , Mehendiratta Vaibhav , Del Galdo Francesco , Jimenez Sergio A. , Cohen Sidney , DiMarino Anthony J. , Rattan Satish
Published: September 2009

Systemic sclerosis (SSc) IgGs affecting the M3-muscarinic receptor (M3-R) have been proposed to be responsible for the gastrointestinal (GI) dysmotility in this disease. However, the effect of SSc IgGs on smooth muscle cell (SMC) function has not been studied. We determined the effect of SSc IgGs on the muscarinic receptor activation by bethanechol (BeCh; methyl derivate of carbachol) in SMC and smooth muscle strips from rat internal anal sphincter. IgGs were purified from GI-symptomatic SSc patients and normal volunteers, with protein G-Sepharose columns. SMC lengths were determined via computerized digital micrometry. The presence of M3-R and IgG-M3-R complex was determined by Western blot. IgGs from SSc patients but not from normal volunteers caused significant and concentration-dependent inhibition of BeCh response ( P < 0.05). The maximal shortening of 22.2 ± 1.2% caused by 10−4M BeCh was significantly attenuated to 8.3 ± 1.2% by 1 mg/ml of SSc IgGs ( P < 0.05). Experiments performed in smooth muscle strips revealed a similar effect of SSc IgG that was fully reversible. In contrast to the effect on BeCh, the SSc IgGs caused no significant effect ( P > 0.05) on K+depolarization and α1-adrenoceptor activation by phenylephrine. Western blot studies revealed the specific presence of SSc IgG-M3-R complex. SSc IgGs attenuated M3-R activation, which was reversible with antibody removal. These data suggest that SSc GI dysmotility may be caused by autoantibodies that inhibit the muscarinic neurotransmission. Future treatment of SSc patients may be directed at the removal or neutralization of these antibodies.
An adaptive transfer function for deriving the aortic pressure waveform from a peripheral artery pressure waveform
Authors: Swamy Gokul , Xu Da , Olivier N. Bari , Mukkamala Ramakrishna
Published: September 2009

We developed a new technique to mathematically transform a peripheral artery pressure (PAP) waveform distorted by wave reflections into the physiologically more relevant aortic pressure (AP) waveform. First, a transfer function relating PAP to AP is defined in terms of the unknown parameters of a parallel tube model of pressure and flow in the arterial tree. The parameters are then estimated from the measured PAP waveform along with a one-time measurement of the wave propagation delay time between the aorta and peripheral artery measurement site (which may be accomplished noninvasively) by exploiting preknowledge of aortic flow. Finally, the transfer function with its estimated parameters is applied to the measured waveform so as to derive the AP waveform. Thus, in contrast to the conventional generalized transfer function, the transfer function is able to adapt to the intersubject and temporal variability of the arterial tree. To demonstrate the feasibility of this adaptive transfer function technique, we performed experiments in 6 healthy dogs in which PAP and reference AP waveforms were simultaneously recorded during 12 different hemodynamic interventions. The AP waveforms derived by the technique showed agreement with the measured AP waveforms (overall total waveform, systolic pressure, and pulse pressure root mean square errors of 3.7, 4.3, and 3.4 mmHg, respectively) statistically superior to the unprocessed PAP waveforms (corresponding errors of 8.6, 17.1, and 20.3 mmHg) and the AP waveforms derived by two previously proposed transfer functions developed with a subset of the same canine data (corresponding errors of, on average, 5.0, 6.3, and 6.7 mmHg).
Acute Behavioral Effects of Intrapleural OK-432 (Picibanil) Administration in Preterm Fetal Sheep
Authors: Cowie Rosalind V. , Stone Peter R. , Parry Emma , Jensen Ellen C. , Gunn Alistair J. , Bennet Laura
Published: September 2009

Objective: To develop a model to study the fetal effects of intrapleural infusion of OK-432 (Picibanil), a pleurodesis agent derived from killed Gram-positive streptococci. Methods: OK-432 (0.1 mg, n = 5), or normal saline (n = 5) were infused over 20 min into the pleural space of chronically instrumented preterm fetal sheep at 0.7 gestation. Fetal physiological parameters, including breathing and nuchal activity were monitored in utero from 6 h before infusion until 12 h afterward, and fetuses were killed after 7 days recovery. Results: OK-432 was associated with transient suppression of fetal EEG activity, breathing and body movements from 3–6 h after infusion. Hypotension and hypoxia did not occur. At postmortem, local pleural adhesions were seen around the site of OK-432 infusion but not in saline treated fetuses. Conclusions: Intrapleural administration of OK-432 is associated with marked but transient fetal behavioral effects. This model will enable preclinical investigation of the neural and cardiovascular safety of OK-432 at a clinical relevant stage of development.
Antenatal Diagnosis and Perinatal Management of Extremely Giant Fetal Cervicopharyngeal Teratoma Resulting in Impossible Fetal Intubation: A Case Report
Authors: Awonuga Awoniyi O. , Bell Jason , Vallecilla Diana , Ray Chad , Yingling Dave , Helfgott Andrew
Published: September 2009

We report the case of an extremely large giant neck teratoma diagnosed on routine sonogram and confirmed by 3-D and 4-D sonography and MRI in a 19-year-old primigravida at 18 weeks. Rapid growth, polyhydramnios, premature contractions and premature rupture of membranes necessitated delivery at 28 weeks. Under general anesthesia, with a multidisciplinary team attendant, efforts by the otolaryngologist to establish an airway during an EXIT (ex utero intrapartum treatment) procedure failed as did subsequent attempts by the neonatologist, leading to an early neonatal death. Although a team approach will increase the likelihood of success in securing the airway during EXIT procedures, it cannot be a guarantor in cases of giant neck teratoma.
Occurrence and Properties of Fetal Intestinal Glycosidases (Disaccharidases) in Human Amniotic Fluid
Authors: Potier M. , Dallaire L. , Melançon S.B.
Published: September 2009

α-Glucosidase, β-glucosidase and β-galactosidase were studied in cell-free amniotic fluid samples using corresponding 4-methylumbelliferyl-glycosides and a series of disaccharides (maltose, sucrose, trehalose, turanose, cellobiose, gentiobiose and lactose) as substrates. The glycosidases exhibited several properties of intestinal disaccharidases such as pH optimum between 5.2 and 6.4, more activity towards the disaccharides than the artificial substrates, tight association of the activities with sedimentable complexes and β-glucosidase and β-galactosidase activities exerted by a single catalytic site. With the disaccharides as substrates, the amniotic fluid glycosidase activities were well correlated to those reported in the literature for fetal intestine of corresponding gestational ages. The presence of intestinal disaccharidases in amniotic fluid indicates that the fetal intestine contributes to the protein and enzymes of amniotic fluid.
Three Years Experience in Preventing Severe Hyperbilirubinemia in Newborn Infants with Erythrocyte G-6-PD Deficiency
Authors: Meloni Tullio , Costa Sinfarosa , Cutillo Stefano
Published: September 2009

Prophylactic treatment with barbituric acid has been made for preventing severe hyperbilirubinemia in G-6-PD deficient newborn infants. In 17 out of 46 untreated and in 7 out of 171 treated cases exchange transfusions were needed since the biliriibin serum level exceeded 18 mg/100 ml. These data show that this prevention can be useful in areas, such as Sardinia, where the incidence of G-6-PD deficiency is very high. It has been further demonstrated that this particular form of neonatal hyperbilirubinemia is not due to increased red cell destruction.
Changes in the Organs of Pigs in Response to Feeding for the First 24 h after Birth
Authors: Stoddart R.W. , Widdowson E.M.
Published: September 2009

The duodenum, jejunum, ileum and large intestine of newborn, and 24-hour-old fed and unfed piglets, and of 10-day-old piglets have been studied by new histochemical methods. At birth Meissner’s plexus was most developed in the duodenum. There was little change during the first 24 h, but by 10 days it had become elaborated. Goblet cells were present at birth in all parts of the intestine. After 24 h a large proportion of those in the duodenum had discharged and were being replaced with a new generation. Similar changes took place more slowly in the jejunum and ileum and very much more slowly in the large intestine. Feeding increased the rate of turnover.
Topography of Lesions in Newborn and Infant Brains following Cardiac Arrest and Resuscitation
Authors: Dambska Maria , Dydyk Lubomira , Szretter T. , Wozniewicz J. , Myers R.E.
Published: September 2009

The brain lesions produced by temporary arrest of circulation in a newborn and an 11-month-old infant are described. In the newborn, two periods of arrest occurred, one on the fifth day after birth and the second a few days before death on the sixth week. The older infant suffered a single episode of cardiac arrest at the age of 11 months and survived 8 days. In both cases, postmortem examination revealed lesions in spinal cord, in brain stem, and in cerebral hemispheres. This distribution of damage is compared with the patterns of injury produced experimentally by episodes of partial (hypoxia) and total (anoxia) asphyxia in subhuman primates. The coexistence of hemispheral and brain stem nuclear patterns of pathology indicates that both hypoxia and anoxia had occurred in the present cases.
Alanine 14C Incorporation into Liver and Skeletal Muscle Proteins during the Early Postnatal Period in the Rat
Authors: Ferré P. , Girard J.R.
Published: September 2009

A sharp decrease in 14C-alanine incorporation into liver and skeletal muscle proteins occurs immediately after birth and again during a fast of 16 h. In the 16-hour-old newborn rats which have been allowed to suckle normally after birth, the muscle and liver protein contents and the incorporation of labeled alanine into proteins are much higher than in starved animals. There is a close correlation between the activity of protein synthesis in liver and muscle and the plasma insulin level. This suggests an important role for insulin in protein metabolism of the newborn rat. The low activity of gluconeogenesis from alanine in fasted newborn rats cannot be accounted for by an overutilization of alanine for protein synthesis. It is suggested that the high fat diet of suckling rats could stimulate alanine production by peripheral tissue and in turn could increase gluconeogenesis.
High Maternal Serum Alkaline Phosphatase as an Index of Meconial Amniotic Fluid
Authors: Brandes Joseph M. , Atad Jack , Zuckerman Henryk
Published: September 2009

High level of maternal serum alkaline phosphatase (AP) (above 4 Bessey-Lowry units) was found to be indicative of meconium-stained amniotic fluid (AF). Simultaneous maternal serum AP and AF AP were measured in two groups: group A, the study group (78 cases), parturients with meconium-stained AF, and group B (29 cases), the control group, parturients with clear AF. A positive significant correlation was found between the level of AP in the AF and the level of AP in the parturient’s serum, when meconium was present. It is our feeling that the high level of AP in the maternal serum is due to transfer of heat-labile AP from the meconium-stained AF, meconium being rich in AP. The mechanism has as yet to be elucidated.
Effect of Hypothyroidism on Aspartate Transcarbamylase, Uridine Kinase, and DNA Biosynthesis during Cerebellar Development in the Rat
Authors: Weichsel, jr. Morton E. , Clark Brian R. , Poland Russell E.
Published: September 2009

Experimental hypothyroidism in the neonatal rat is known to retard cerebellar DNA biosynthesis with a return to normal of the ultimate cell number. Because of the known shift to a later age in the developmental curve for cerebellar thymidine kinase in hypothyroid rats, we studied the activities of aspartate transcarbamylase (ATC) and uridine kinase (UK) during cerebellar development in rats rendered hypothyroid by daily intragastric administration of propylthiouracil to the mother after 18 days gestation. Body weight and cerebellar wet weight in treated animals were noted to be significantly decreased below control values by day 5. Cerebellar DNA was significantly decreased below control values by day 5 with a maximum deficit of 64.9% of control on day 9, and a decrease in deficit to 80.9% of control on day 21. ATC activity in cerebella of hypothyroid rat pups was significantly below that of controls at age 5 days, and by age 15 and 21 days was significantly elevated above control values (91.4, 116, and 154% of controls respectively), thus suggesting a shift to a later age for activity of this enzyme in the hypothyroid state. UK activity in cerebella of hypothyroid pups was significantly below that of activity in control cerebella at age 5 days, but was not significantly different from controls at any of the later ages. Activity of UK in both treated and control cerebella remained relatively elevated by age 21 days with respect to the maximum activity in controls at age 9 days. The shift to a later age in the developmental spectrum of cerebellar ATC activity, an enzyme representative of the de novo pathway for pyrimidine biosynthesis, suggests that the enzyme is involved in the mechanism whereby cerebellar cell division is suppressed and subsequently prolonged in the hypothyroid state. The lack of an influence of hypothyroidism on cerebellar UK activity after day 5 of development supports previous observations that this enzyme may relate in brain to the synthesis of RNA and to cell functions not specifically related to proliferation. The study reveals the differential effects of neonatal hypothyroidism on enzymes representing two of the pathways involved in pyrimidine and nucleic acid biosynthesis during the thyroid hormone-sensitive period of early mammalian brain development, and emphasizes the necessity for further biochemical studies involving tissue pool sizes of in vivo intermediates and serum concentrations of nucleic acid precursors in order to further delineate the relative contribution of each pathway essential for nucleic acid metabolism during development.
Rodent Brain Growth Stages: An Analytical Review
Authors: Gottlieb A. , Keydar I.K. , Epstein H.T.
Published: September 2009

Study of data in the literature on rat and mouse brain growth from birth to weaning reveals a stagewise growth in average brain weight. Rapid growth occurs in the intervals between days 0–6, 8–12, and 17–23 after birth. Slow growth periods then lie in the intervals 6–8, 12–17, and after 23 days. The first slow growth period is signalled by events occurring at its end: substantial acceleration of synthesis of RNA, DNA, protein, and myelin. The second slow growth period is characterized by at least a 3-day interval during which there is very little increase in average brain weight compared with what occurs just before and just after that period; the correlation among 12 studies is highly significant. Implications are discussed for cross-species’ extrapolation of findings about brain development.
In vitro Effects of Inosine-Pyruvate-Phosphate on P50 Values and DPG Contents of Fresh and Stored Blood from Healthy Neonates, Symptom-Free Premature Infants and Premature Infants with Respiratory Distress Syndrome
Authors: Boda D. , Eck E.
Published: September 2009

A study was made of the effect of a 3-hour incubation with inosine-pyruvate-phosphate (IPP) on the P50 values and 2,3-DPG contents of fresh blood and blood which had stood for 96 h, from healthy adults, term neonates, 1–2-week-old symptom-free premature infants and RDS premature infants. It was found that the P50 value and the 2,3-DPG content could be increased considerably by IPP treatment in both the fresh and the stood blood in the various groups of neonates. The question remains open as to whether the effect of IPP, in significantly improving the O2 transport in neonates, is a consequence of the 2,3-DPG alone or of some other metabolite. In RDS the stimulating effect of the IPP mixture is appreciably lower.
The Effects of Maternal Phlebotomy and Orally-Administered Erythropoietin (Ep) on Erythropoiesis in the Suckling Rat
Authors: Carmichael Robert D. , Gordon Albert S. , LoBue Joseph
Published: September 2009

Erythropoiesis was stimulated in 2- to 5-day-old neonatal rats suckled by phlebotomized mothers. This was established by increases in: hemoglobin levels, mean corpuscular hemoglobin concentration and percentages of peripheral reticulocytes. The oral administration of cow milk containing 4 IU human erythropoietin (Ep) to 10-day-old normal neonates for 4 days induced a reticulocytosis. Significant amounts of Ep appeared in the plasma of 1-day-old rats nursed by mothers bled 3 days prior to delivery as compared to nondetectable levels in 1-day-old control rats of normal mothers. The data suggest that Ep is transmitted to neonatal rats via maternal milk, and escapes inactivation, at least to some extent, in the process of absorption from the gastrointestinal tract with consequent stimulation of erythropoiesis in these animals.
Hormonal Regulation of Three Urea Cycle Enzymes in Rat Fetal Liver
Authors: Husson A. , Vaillant R.
Published: September 2009

The purpose of such studies is to identify the hormones that act on the developmental formation of individual urea cycle enzymes, namely argininosuccinate synthetase, argininosuccinate lyase and arginase in the rat fetal liver. The development of argininosuccinate synthetase activity which is completely blocked by the suppression of glucocorticoids in the fetal liver is affected by neither glucagon nor thyroxine. The activity of argininosuccinate lyase which is never changed by the suppression or addition of glucocorticoids, is under the influences of glucagon and thyroxine at a late fetal period and the enzyme activity can be precociously induced in utero by injection of dibutyryl cyclic AMP to fetuses. Cortisol has been shown to precociously stimulate fetal liver arginase activity after an intraperitoneal injection, but the rise in activity at the late fetal period is not completely prevented by suppression of glucocorticoid and it seems that glucagon and thyroxine may also promote its developmental formation just before birth.
Intraventricular Hemorrhage – an Animal Model
Authors: Goddard Janette , Lewis Robert M. , Alcala Hilda , Zeller Robert S.
Published: September 2009

Hemodynamic monitoring was carried out in 9 newborn beagle puppies exposed to hypercarbic insult. 4 animals were exposed to slowly increasing carbon dioxide tensions without hypoxemia; 5 animals were exposed to rapid, intense increases in carbon dioxide tensions without hypoxemia. 2 of the 5 puppies (40%) exposed to the rapid hypercarbia developed intraventricular hemorrhage characteristic of that found in the immature human. All of the puppies exhibited germinal matrix layers comparable to those of 30- to 32-week gestational age human infants. Significantly higher systemic arterial and jugular venous pressures were documented during the baseline and experimental periods in the 2 animals that bled. A predisposition to hemorrhage may have been present in these 2 animals because of hypertension in the baseline period. This preliminary study demonstrates that a histological model for IVH exists in an animal which is stable enough for extensive hemodynamic monitoring.
Effect of Gestational Alloxan Diabetes and Fasting on Fetal Lipogenesis and Lipid Deposition in Pigs
Authors: Kasser T.R. , Martin R.J. , Allen C.E.
Published: September 2009

Experiments were conducted in pregnant pigs to determine the influence of alloxan diabetes and maternal fasting on fetal development. Maternal fasting and alloxan diabetes both increased adipose tissue thickness in fetuses at 112 days of gestation without altering body weight. Body fat was increased quantitatively only in the fetuses from the diabetic pigs (FDP). Apparently, different factors were affecting the structural development of adipose tissue and the actual storage of lipid. Fetal and maternal hepatic fatty acid synthesis were unaffected by treatments. Maternal subcutaneous adipose fatty acid synthesis was depressed by 75% in both fasted and diabetic dams while subcutaneous adipose tissue lipogenesis was increased 40-fold in the FDP. Enzymes normally associated with lipogenesis (shunt enzymes) were also affected in a similar fashion. These observations support the concept that fetal adipose de novo fatty acid synthesis is stimulated by diabetic pregnancies and is a primary mechanism by which increased lipid accumulates in the fetus.
The Effect of 3,5,3′-Triiodothyronine on Phosphoenolpyruvate Carboxykinase, Fatty Acid Synthetase and Malic Enzyme Activity of Liver and Brown Fat of Fetal and Neonatal Rats
Authors: Hahn Peter , Hassanali Salim
Published: September 2009

Pregnant rats were injected with triiodothyronine (T3) on the 19th and 20th days of pregnancy. This elevated fetal T3 plasma values and caused a large rise in fetal liver phosphoenolpyruvate carboxykinase (PEPcK) activity. At the same time PEPcK activity in fetal brown fat was inhibited. Essentially the same effect of T3 was also noted when injected into postnatal rats. T3 injections also elevated fatty acid synthetase activity in brown fat of weanling rats but, in contrast to corticosteroids, had no effect earlier in life. No effect was noted in the liver, except a slight decrease in the fetus. T3 injections to suckling rats elevated plasma levels of insulin and glucagon within 24 h.
Intrauterine Growth Retardation and Development of Endocrine Pancreas in the Experimental Rat
Authors: De Prins F.A. , Van Assche F.A.
Published: September 2009

Intrauterine growth retardation (IUGR) was induced in rats by uterine artery ligation according to Wigglesworth. Control and growth-retarded animals were studied at days 21 and 22 of fetal life and 2 h after spontaneous birth. Fetuses with IUGR, when compared to controls, showed significantly lower glycemia and insulinemia levels. Newborn rats with IUGR had reduced glycemia levels but identical insulin values in comparison to controls. Dysmature and control animals had significantly different absolute weights of endocrine pancreas, but they had equal amounts of endocrine pancreatic tissue in proportion to their total body weight. Within the endocrine pancreas the same number of islet cells was counted in dysmature and control animals, but the animals with IUGR ended up with a reduced percentage of insulin-containing granulated B cells after birth.
Free Thyroid Hormone Levels during the Postnatal Period in the Pig
Authors: Nowak G.
Published: September 2009

Sequential observations on serum concentrations of dialyzable (DFT4, %) and absolute free thyroxine (FT4), free triiodothyronine (FT3) and free reverse-triiodothyronine (FrT3) were conducted in piglets (n = 10) from birth to 21 days of age. Mean FT4 and FT3 were found to be significantly raised during the first 3 days of life, with the highest value (0.520 ± 0.070% DFT4, 551 ± 0.1 pmol/l and 0.965 ± 0.020% DFT3, 18.8 ± 1.2 pmol/l) between 0 and 12 h after birth. Later, a decrease was observed until the end of the first week followed by a steady and relatively low level during the second and third postnatal weeks. Dialyzable fraction of rT3 increased to a peak value at 48 h of age (0.621 ± 0.044%) and then decreased till day 7, showing a steady level during the second and the third weeks of life. Absolute FrT3 concentration remained low and relatively constant except for a higher value (3.76 ± 0.44 pmol/l) between 12 and 24 h after birth. The FT4:FT3 and FT4:FrT3 ratios were high between 0 and 6h of age. The FT3:FrT3 ratio reached the highest value (about 11.0) between the second and fifth days, followed by a fall to 4.7–7.5 during 2–3 weeks after birth.
Late Pregnancy Maternal and Fetal Time-Course of Plasma ACTH and Corticosterone after Continuous Ether Inhalation by Pregnant Rats
Authors: Cohen Alia , Chatelain Alain , Dupouy Jean-Paul
Published: September 2009

In order to compare the time-course and the amplitude of the hypophyseal-adrenal response to stress in both the mother and the fetus, female rats on day 20 of pregnancy were subjected to continuous ether inhalation and killed at different time intervals after the onset of stress (5, 10, 20, 30, 40 and 60 min). Plasma ACTH was determined by radioimmunoassay and plasma corticosterone by a competitive binding radioassay. In normal pregnant rats subjected to ether stress, the release of ACTH is tenfold higher than in the fetus, but the amplitude of maternal and fetal corticosterone release after this stimulus is very similar; the response occurs faster in the mother than in the fetus. In pregnant rats adrenalectomized 4 h before ether stress procedure, the ACTH release is smaller than in normal mothers and the plasma corticosterone values, despite the adrenalectomy, are close to those observed in resting rats at the same time of day. The fetal corticosterone release is still elevated under this stimulus and occurs faster than in fetuses from normal mothers. The cytoimmunological study of fetal hypophysis revealed both hypertrophy and hyperplasy of ACTH-containing cells during the first minutes of ether anesthesia.
Effect of Glucagon, Phenylephrine, and Isoproterenol on Glycogenolysis and Glucose Release from Fetal Rat Hepatocytes in Suspension
Authors: Hühn W. , Schulze H.-P. , Dargel R.
Published: September 2009

Fetal hepatocytes isolated at day 22 of gestation by trypsin digestion of rat liver retain their responsiveness to hormones. Glucagon significantly stimulates glycogenolysis and glucose release to 115 and 124%, respectively. The effect of α- and β-agonists is more pronounced enhancing glycogen breakdown and glucose release to 133 and 147% (L-phenylephrine) and 183 and 202% (isoproterenol), respectively. The isolated fetal hepatocytes obtained by trypsin digestion are a useful tool for studying the hormonal control of liver metabolism during the perinatal stage without limitations met otherwise with extrahepatic factors and the effect of altered blood flow.
Development of the Lipolytic Activity in Isolated Perfused Perinatal Rabbit Lungs and the Influence of Maternal Cigarette Smoke Exposure on It
Authors: Simberg Niklas , Hartiala Jaakko , Hietanen Eino
Published: September 2009

The ability of the lungs to release fatty acids from circulating triglycerides or lipoproteins for its own phospholipid synthesis may be one of the factors which limit the rate of surfactant formation. Therefore, the development of the lipolytic activity of lungs obtained from late fetal and neonatal rabbits has been studied and the results correlated to the phospholipid content of lungs of similar ages. Isolated lungs were perfused with a medium which contained cold and radioactive triglyceride, and the release of fatty acids into the perfusion medium was analyzed by both colorimetric and radiochemical methods. The phospholipids of the postmitochondrial supernatant fractions of the lungs were extracted and quantified by measuring inorganic phosphorus. Finally, the influence of maternal cigarette smoke exposure on the lipolytic activity of the lungs of their litters were studied. A high lipolytic activity in the lungs of 2 8-day-old fetuses was detected. The activity decreased towards birth, and was lowest on the first day after birth (about 20% of that observed in 28-day-old fetuses). However, it increased again during the first week after birth. Exposure of the mothers to cigarette smoke during the last 10 days before delivery did not affect the pulmonary lipolytic activity of the offspring. Although the lung phospholipid content increased 3.6-fold from 28 days of fetal life to 1 week after birth, it remained unchanged on the days when the lung lipolytic activity was lowest. We conclude that changes in lung lipolytic activity influence lung phospholipid synthesis, and consequently influence also surfactant formation in the lungs.
Phenotypic Immaturity of T and B Lymphocytes in Cord Blood of Full-Term Normal Neonates
Authors: Lucivero Giacomo , Dell’Osso Adriana , Iannone Aldo , Selvaggi Luigi , Antonaci Salvatore , Bettocchi Silvio , Bonomo Lorenzo
Published: September 2009

We examined mononuclear cell subsets in cord blood of normal newborns by surface marker analysis. The percentages of T lymphocytes (E-rosetting and T3+ cells) were lower in cord blood than in peripheral blood (PB) from adults, while the percentage and absolute number of T6+ cells were higher in cord blood. As the sum of T4+ and T8+ cells exceeded the values of E-rosetting lymphocytes in cord blood, we suggest that immature lymphocytes with the phenotype of ‘common’ thymocytes (T6+, T4+, T8+) are present in cord blood of full-term newborns. Higher percentage and absolute number of B lymphocytes were detected in cord blood. More than 50% of B cells in cord blood formed rosettes with mouse erythrocytes, a surface marker of functional immaturity. Finally, cells bearing receptors for IgG-Fc fragments or C3 and expressing Ia-like and Ml antigens were uniformly increased in cord blood, suggesting higher percentages of cells of the monocytic lineage.
Differences in the Perinatal Development of the Isolated Rabbit Lungs’ Ability to Inactivate Vasoactive Substances
Authors: Olson, Jr. Burt , Rankin† John
Published: September 2009

A 20-second bolus of serotonin (5-hydroxytryptamine, 5HT), prostaglandin E1 (PGE1·) or norepinephrine (NE) was infused into the pulmonary arteries of lungs isolated from 26-day gestation fetal, newborn (within 12 h of birth), and young adult rabbits. In each case the concentration of the infused substrate was much less than the apparent Michaelis constant for the uptake process. At these low concentrations there was no observable vasoactivity. In order to assure a constant ratio of flow to capillary surface area (independent of lung size), perfusate flow was adjusted so that the retention time of a vascular dye was approximately 7 s. Under these conditions the isolated adult rabbit lungs inactivate a similar fraction (40–50%) of each of the substrates. In contrast, isolated newborn rabbit lungs inactivate about 20% of the infused PGE1, 90% of the 5HT, and 60% of the NE, and the nonventilated, previable fetal rabbit lungs inactivate about 20% of the infused PGE1 60% of the 5HT, and 80% of the NE.
Contribution of Heart Muscle, Liver, Skeletal Muscle and Placenta to the Asphyxial Hypoxanthine Elevation in the Acutely Exteriorised Fetal Lamb
Authors: Thiringer Klara , Karlsson Kirsten , Rosén Karl Gustaj , Kjellmer Ingemar
Published: September 2009

The metabolic response to different degrees of hypoxia was studied in 14 lamb fetuses. We have previously found a substantial rise in the fetal arterial plasma hypoxanthine (HX) level, in parallel with alterations of other hypoxia indices during induced asphyxia. Measurements of the arterio-venous (A-V) difference in the HX level across the CNS demonstrated a late efflux of this substance from the fetal brain, with a high resistance to asphyxia. In this study, the effluxes of HX, lactate, and in some cases glucose, from the myocardium, liver, hindleg (skeletal muscle) and placenta were investigated in acutely exteriorised sheep fetuses with graded asphyxia. The main findings were as follows: (a) myocardium: a release of HX early during asphyxia, the magnitude of which paralelled the amount of mechanical work performed by the heart; a significant lactate influx into the heart during normoxia and recovery period; (b) liver: hepatic HX release even during normoxia, increasing to substantial amounts in connection with increasing asphyxia; (c) hindleg: release of HX only during the recovery period; lactate efflux during all periods apart from severe asphyxia, when an influx was seen for both substances; (d) placenta: production of lactate during normoxia, and an efficient clearance of both lactate and HX from the fetal plasma in combination with their concentration increasing during asphyxia. It is concluded that the myocardium and liver are the main contributors to the elevated HX level during fetal asphyxia among the fetal organs investigated, while skeletal muscle releases HX mostly during the period of reoxygenation.
Effect of Cortisone on Intestinal Uptake of Lead in the Suckling Rat
Authors: Henning Susan J. , Leeper Lucy L.
Published: September 2009

A previous study showed that there is extensive uptake of lead by the duodenum and the ileum of the suckling rat. At both sites, uptake declines with advancing age. This paper reports the effects of administration of cortisone acetate on in vivo lead uptake in 14- to 15-day-old rats. The results indicate that the duodenal uptake component is unaffected by hormone treatment whereas the ileal uptake component is markedly suppressed. There was no significant difference in blood lead concentrations in cortisone-treated pups as compared with vehicle-treated controls. We conclude that lead absorption in the suckling rat occurs primarily in duodenum and is not under glucocorticoid control. The ileal uptake of lead probably represents intestinal retention rather than absorption: its responsiveness to cortisone would be consistent with uptake via pinocytosis.
Uptake of Taurocholate by Freshly Isolated Hepatocytes from Fetal and Newborn Rabbits
Authors: Bhat R. , Bernstein M.S. , Anderson R.J. , Vidyasagar D. , Evans M.A.
Published: September 2009

During early postnatal maturation a significant increase in the rate constant of translocation (Michaelis-Menten constant; Km) for taurocholate uptake occurs in isolated rabbit hepatocytes. This age-dependent change is related to a decrease in the efficiency of uptake for taurocholate and is probably associated with changes in the receptor or its microenvironment within the plasma membrane. Cholic acid conjugates (taurocholic and glycocholic acids) are the predominant bile acids found in the premature and neonatal human. It is therefore of interest that in the fetal and neonatal rabbit we have found a developmentally dependent alteration of taurocholic acid transport.
The Genetics of Ficolins
Authors: Garred Peter , Honoré Christian , Ma Ying Jie , Rørvig Sara , Cowland Jack , Borregaard Niels , Hummelshøj Tina
Published: September 2009

Ficolins constitute a family of proteins whose biological role has been an enigma for many years. Over the past few years it has become evident that ficolins are part of the innate immune system and function as recognition molecules in the complement system. The 3 human ficolins, ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin or Hakata antigen) are encoded by the FCN1, FCN2 and FCN3 genes, respectively. Phylogenetic studies suggest that ficolins are of ancient origin. Ficolin-3 seems to be the most ancient molecule, from a phylogenetic perspective. Searches in databases and phylogenetic tree analysis demonstrate that the ficolin precursor has gone through an expansion involving independent duplication events in the different branches of the evolutionary tree. Of particular interest is the prediction that ficolin-1 appears to be present as an ortholog molecule. All human FCN genes are polymorphic. The FCN2 gene encoding ficolin-2, contains polymorphisms that affect ligand binding, while differences in the serum levels are associated with promoter polymorphisms. Recently, a frame-shift variation in the FCN3 gene was described, leading to ficolin-3 deficiency and defective complement activation. This FCN3 variation was also shown to be associated with immunodeficiency. This survey summarizes the current phylogenetic and inter-individual molecular understanding of the FCN genes.
Pathogenesis of Bronchopulmonary Dysplasia
Authors: Hayes, Jr. Don , Feola David J. , Murphy Brian S. , Shook Lori A. , Ballard Hubert O.
Published: September 2009

Bronchopulmonary dysplasia (BPD) refers to a heterogeneous group of lung disorders in infants that is commonly associated with prematurity and surfactant deficiency. BPD results from the complex interplay between impairments in the premature lung such as surfactant deficiency, perinatal insults such as infection, and damage resulting from supportive care of the infant due to barotrauma or volutrauma from mechanical ventilation and oxygen toxicity from supplemental oxygen administration. These factors result in chronic inflammation in the infant lung with recurring cycles of lung damage and repair that may impair alveolarization and vascularization in the developing lungs. As our insight in how to treat BPD improves along with the ability to do so with developing technology and therapies, the underlying pathogenesis will also change. The term ‘new’ BPD is now commonly used, to describe the changes seen in the post-surfactant era. This discussion reviews the pathogenesis of BPD according to the current medical literature.
Adherence to Continuous Positive Airway Pressure Therapy for Obstructive Sleep Apnea: Impact of Patient Education after a Longer Treatment Period
Authors: Fuchs Florian S. , Pittarelli Adriano , Hahn Eckhart G. , Ficker Joachim H.
Published: September 2009

Background: Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA) but it is often cumbersome so that adherence to CPAP therapy is limited. Objectives: We evaluated adherence to CPAP therapy after an additional educative intervention in OSA patients after a longer treatment period. Methods: A short patient information program covering many aspects of symptoms, consequences and treatment of OSA was created, and standardized information sessions were developed to be given by an experienced sleep physician to >6,000 participants of patient support group meetings throughout Germany. They also received a booklet containing the essential information of the lectures. Of the 526 randomly selected members of these support groups receiving the anonymized questionnaire by mail, 475 CPAP patients sent the questionnaire back. Of these CPAP patients, 243 participated in a lecture und and had received a booklet (information group) and 232 CPAP patients had not attended a lecture (control group). Results: In the information group, a significantly higher daily usage of CPAP devices (6.9 ± 0.9 h/day) was reported compared with the control group (5.7 ± 1.3 h/day; p < 0.001). Furthermore, the score in the Epworth Sleepiness Scale (ESS) was found to be significantly lower in the information group (median ESS = 6, interquartile range, IQR, 4–8 vs. median = 11, IQR 8–13; p < 0.001). Conclusions: Patients who attended our short information program showed a higher daily usage and a lower subjective daytime sleepiness. These results suggest that patients on CPAP therapy may benefit from education even after a longer treatment period.
In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons
Authors: Hickok Jason R. , Tischkau Shelley A.
Published: September 2009

Although it is generally accepted that the circadian clock provides a timing signal for the luteinizing hormone (LH) surge, mechanistic explanations of this phenomenon remain underexplored. It is known, for example, that circadian locomotor output cycles kaput (clock) mutant mice have severely dampened LH surges, but whether this phenotype derives from a loss of circadian rhythmicity in the suprachiasmatic nucleus (SCN) or altered circadian function in gonadotropin-releasing hormone (GnRH) neurons has not been resolved. GnRH neurons can be stimulated to cycle with a circadian period in vitro and disruption of that cycle disturbs secretion of the GnRH decapeptide. We show that both period-2 (PER2) and brain muscle Arnt-like-1 (BMAL1) proteins cycle with a circadian period in the GnRH population in vivo. PER2 and BMAL1 expression both oscillate with a 24-hour period, with PER2 peaking during the night and BMAL1 peaking during the day. The population, however, is not as homogeneous as other oscillatory tissues with only about 50% of the population sharing peak expression levels of BMAL1 at zeitgeber time 4 (ZT4) and PER2 at ZT16. Further, a light pulse that induced a phase delay in the activity rhythm of the GnRH-eGFP mice caused a similar delay in peak expression levels of BMAL1 and PER2. These studies provide direct evidence for a functional circadian clock in native GnRH neurons with a phase that closely follows that of the SCN.
Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia
Authors: Koike Tomonari , Kitajima Shuji , Yu Ying , Li Ying , Nishijima Kazutoshi , Liu Enqi , Sun Huijun , Waqar Ahmed Bilal , Shibata Nobumitsu , Inoue Tomoriho , Wang Yao , Zhang Bo , Kobayashi Junji , Morimoto Masatoshi , Saku Keijiro , Watanabe Teruo , Fan Jianglin
Published: September 2009

Objective—

Apolipoprotein AII (apoAII) is the second major apolipoprotein in high-density lipoprotein (HDL). However, the physiological functions of apoAII in lipoprotein metabolism have not been fully elucidated.

Methods and Results—

We generated human apoAII transgenic (Tg) rabbits, a species that normally does not have an endogenous apoAII gene. Plasma levels of human apoAII in Tg rabbits were ≈30 mg/dL, similar to the plasma levels in healthy humans. The expression of human apoAII in Tg rabbits resulted in increased levels of plasma triglycerides, total cholesterol, and phospholipids accompanied by a marked reduction in HDL-cholesterol levels compared with non-Tg littermates. Analysis of lipoprotein fractions showed that hyperlipidemia exhibited by Tg rabbits was caused by elevated levels of very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins. Furthermore, postheparin lipoprotein lipase activity significantly decreased in Tg rabbits compared with non-Tg rabbits.

Conclusions—

These results indicate that apoAII plays an important role in both VLDL and HDL metabolism, possibly through the inhibition of lipoprotein lipase activity. ApoAII Tg rabbits may become a new model for the study of human familial combined hyperlipidemia.
Tumor Necrosis Factor–Like Weak Inducer of Apoptosis (TWEAK) Enhances Vascular and Renal Damage Induced by Hyperlipidemic Diet in ApoE-Knockout Mice
Authors: Muñoz-García Begoña , Moreno Juan Antonio , López-Franco Oscar , Sanz Ana Belén , Martín-Ventura José Luis , Blanco Julia , Jakubowski Aniela , Burkly Linda C. , Ortiz Alberto , Egido Jesús , Blanco-Colio Luis Miguel
Published: September 2009

Objective—

Tumor necrosis factor–like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice.

Methods and Results—

ApoE
−/−
mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 μg/kg/d), anti-TWEAK neutralizing mAb (1000 μg/kg/d), TWEAK plus anti-TWEAK antibody (10 μg TWEAK +1000 μg anti-TWEAK/kg/d), or nonspecific IgG (1000 μg/kg/d) daily for 9 days. In ApoE
−/−
mice, exogenous TWEAK administration in ApoE
−/−
mice induced activation of NF-κB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE
−/−
mice with an anti-TWEAK blocking mAb decreased NF-κB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion.

Conclusion—

Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid–rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with hyperlipidemia.
PKA-Dependent Phosphorylation of Serum Response Factor Inhibits Smooth Muscle–Specific Gene Expression
Authors: Blaker Alicia L. , Taylor Joan M. , Mack Christopher P.
Published: September 2009

Objective—

Our goal was to identify phosphorylation sites that regulate serum response factor (SRF) activity to gain a better understanding of the signaling mechanisms that regulate SRF’s involvement in smooth muscle cell (SMC)-specific and early response gene expression.

Methods and Results—

By screening phosphorylation-deficient and mimetic mutations in SRF
−/−
embryonic stem cells, we identified T159 as a phosphorylation site that significantly inhibits SMC-specific gene expression in an embryonic stem cell model of SMC differentiation. This residue conforms to a highly conserved consensus cAMP-dependent protein kinase (PKA) site, and in vitro and in vivo labeling studies demonstrated that it was phosphorylated by PKA. Results from gel shift and chromatin immunoprecipitation assays demonstrated that T159 phosphorylation inhibited SRF binding to SMC-specific CArG elements. Interestingly, the myocardin factors could at least partially rescue the effects of the T159D mutation under some conditions, but this response was promoter specific. Finally, PKA signaling had much less of an effect on c-fos promoter activity and SRF binding to the c-fos CArG.

Conclusions—

Our results indicate that phosphorylation of SRF by PKA inhibits SMC-specific transcription suggesting a novel signaling mechanism for the control of SMC phenotype.
Mechanisms Underlying Skeletal Muscle Weakness in Human Heart Failure
Authors: Miller Mark S. , VanBuren Peter , LeWinter Martin M. , Lecker Stewart H. , Selby Donald E. , Palmer Bradley M. , Maughan David W. , Ades Philip A. , Toth Michael J.
Published: September 2009

Background—

Patients with chronic heart failure (HF) frequently experience skeletal muscle weakness that limits physical function. The mechanisms underlying muscle weakness, however, have not been clearly defined.

Methods and Results—

This study examined the hypothesis that HF promotes a loss of myosin protein from single skeletal muscle fibers, which in turn reduces contractile performance. Ten patients with chronic HF and 10 controls were studied. Muscle atrophy was not evident in patients, and groups displayed similar physical activity levels, suggesting that observed differences reflect the effects of HF and not muscle atrophy or disuse. In single muscle fibers, patients with HF showed reduced myosin heavy chain protein content (
P
<0.05) that manifested as a reduction in functional myosin-actin cross-bridges (
P
<0.05). No evidence was found for a generalized loss of myofilament protein, suggesting a selective loss of myosin. Accordingly, single muscle fiber maximal Ca
2+
-activated tension was reduced in myosin heavy chain I fibers in patients (
P
<0.05). However, tension was maintained in myosin heavy chain IIA fibers in patients because a greater proportion of available myosin heads were bound to actin during Ca
2+
activation (
P
<0.01).

Conclusions—

Collectively, our results show that HF alters the quantity and functionality of the myosin molecule in skeletal muscle, leading to reduced tension in myosin heavy chain I fibers. Loss of single fiber myosin protein content represents a potential molecular mechanism underlying muscle weakness and exercise limitation in patients with HF.