Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep.

Objective: The aim of this study was to investigate functional development of small arteries from the skeletal circulation of fetal sheep and to determine whether maternal undernutrition affects responses to vasoconstrictive and vasodilatory agonists in arteries from the late-gestation fetus.

Study Design: We investigated vasoconstrictive and vasodilatory responses of isolated small (approximately 300 microm) arteries from the femoral vascular bed of fetal sheep and from late-gestation pregnant ewes. Ewes were fed either 100% of the nutritional requirement throughout pregnancy (control group) or a restricted diet of 85% or 50% of the nutritional requirement for the first 70 days of pregnancy.

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep.

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins.

Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b.

The signalling thresholds of antigen receptors and co-stimulatory receptors determine immunity or tolerance to self molecules. Changes in co-stimulatory pathways can lead to enhanced activation of lymphocytes and autoimmunity, or the induction of clonal anergy. The molecular mechanisms that maintain immunotolerance in vivo and integrate co-stimulatory signals with antigen receptor signals in T and B lymphocytes are poorly understood.

The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes.

Topical vitamin D3 has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D3 analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D3 (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis.

Mechanisms of noradrenaline-induced vasorelaxation in isolated femoral arteries of the neonatal rat.

Isolated arteries from the femoral circulation of Wistar rats mounted on a small vessel myograph demonstrated age related tension development to noradrenaline (NA, 1 x 10(-8) - 5 x 10(-5) M) day 20 greater than day 10 (P<0.005); day 100 greater than day 20 (P<0.001) and depolarizing potassium (125 mM) buffer day 20 greater than day 10 (P<0.

Goat fetuses disconnected from the placenta, but reconnected to an artificial placenta, display intermittent breathing movements.

To investigate whether placental factors are involved in the intermittent breathing movements in goat fetuses, we assessed electrocortical activity (ECoA) and tracheal pressure in 5 fetuses (124-135 days) separated from the placenta and connected for 48 h to an extrauterine fetal incubation system that provided umbilical arteriovenous extracorporeal membrane oxygenation. The fetal physiological condition on this system was almost the same as that in utero for at least 48 h after the preparation. All fetuses showed intermittent low-voltage ECoA and breathing movements.

Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4.

The stress signaling kinase SEK1/MKK4 is a direct activator of stress-activated protein kinases (SAPKs; also called Jun-N-terminal kinases, JNKs) in response to a variety of cellular stresses, such as changes in osmolarity, metabolic poisons, DNA damage, heat shock or inflammatory cytokines. We have disrupted the sek1 gene in mice using homologous recombination. Sek1(-/- )embryos display severe anemia and die between embryonic day 10.

Activation of c-Jun N-terminal kinase (JNK) by lysophosphatidic acid in Swiss 3T3 fibroblasts.

Lysophosphatidic acid (LPA) induced activation of c-Jun N-terminal kinase (JNK) in Swiss 3T3 fibroblasts. This activation reached the maximum at 20 min and required a high concentration of LPA with an EC50 value of approximately 3 microg/ml. LPA-induced activation of JNK was not suppressed by prior treatment of the cells with pertussis toxin, whereas it was completely blocked by suramin, a non-selective inhibitor of ligand-receptor interactions.

Impaired TCR-mediated apoptosis and Bcl-XL expression in T cells lacking the stress kinase activator SEK1/MKK4.

The dual specificity kinase SEK1 (MKK4) is a direct activator of stress-activated protein kinases (SAPK/JNK) in response to environmental stresses or mitogenic factors. We show in Sek1(-/-)Rag(-/-) chimeric mice that a Sek1 null mutation augments the susceptibility of peripheral T cells to TCR/CD3 religation-induced apoptosis. Sek1(-/-) T cells failed to induce expression of the death suppressor Bcl-XL in response to Ag receptor activation.

Molecular mechanism of human CD38 gene expression by retinoic acid. Identification of retinoic acid response element in the first intron.

CD38 is a nonlineage-restricted type II transmembrane glycoprotein possessing ecto-NAD+ glycohydrolase activity. Because of its unique expression pattern in lymphocyte differentiation, it appears to function as an immunoregulatory molecule. We previously reported that CD38 was specifically induced by all-trans-retinoic acid (RA) in human promyelocytic leukemia HL-60 cells.

Upper cervical myelopathy associated with low CSF pressure: a complication of ventriculoperitoneal shunt.

A patient who had undergone ventriculoperitoneal shunting developed upper cervical myelopathy. His CSF pressure was markedly low, and deformation of the spinal cord and shrinkage of the subarachnoid space at the upper cervical level were found in radiologic examinations. Ligation of the shunt tube resulted in almost complete recovery.

Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor.

Background: Vav is a guanine-nucleotide exchange factor for the Rho-like small GTPases RhoA, Rac1 and Cdc42, which regulate cytoskeletal reorganization and activation of stress-activated protein kinases (SAPK/JNKs). Vav is expressed in hematopoietic cells and is phosphorylated in T and B cells following activation of various growth factor or antigen receptors. Vav interacts with several signaling molecules in T cells, but the functional relevance of these interactions is established only for Slp76: they cooperate to induce activity of the transcription factor NF-AT and interleukin-2 expression.

Differential developmental process of respective behavioral states in human fetuses.

The presence of behavioral states has been recognized in human fetuses. However, developmental process of fetal behavioral states remains to be clarified. In thirty-one normal pregnant women between 20 and 41 weeks' gestation, fetal movements were examined by using multiple ultrasonic machines.

The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production.

NF-ATc1 is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In activated T cells, nuclear NF-AT binds to the promoter regions of multiple cytokine genes and induces their transcription. The role of NF-ATc1 was investigated in recombination activating gene-1 (RAG-1)-deficient blastocyst complementation assays using homozygous NF-ATc1-/- mutant ES cell lines.

Activation of stress-activated protein kinases/c-Jun N-terminal protein kinases (SAPKs/JNKs) by a novel mitogen-activated protein kinase kinase.

Mitogen-activated protein kinase (MAPK) kinases (MKKs) are dual-specificity protein kinases that phosphorylate and activate MAPK. We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open reading frame of 347 amino acids with 11 kinase subdomains.

An evaluation of the system to control blood flow in maintaining goat fetuses on arterio-venous extracorporeal membrane oxygenation: a novel approach to the development of an artificial placenta.

We compared various methods to control blood flow for extrauterine incubation of goat fetuses without lung respiration using arterio-venous extracorporeal membrane oxygenation via umbilical vessels to develop a suitable system for a long-term life support system for premature neonates. In twenty-seven consecutive preparations of goat fetuses, 4 designs (System 1, manual flow control without a reservoir; System 2, manual flow control with an arterial open-top reservoir; System 3, semiautomatic flow control with an arterial open top reservoir; and System 4, semiautomatic flow control with a tube occluder and an arterial open top reservoir) were tested in terms of the duration of incubation periods during which fetuses were kept under stable conditions. The incubation periods became prolonged with the advancement of the system (System 1, 5.

Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient.

Neoplastic disorders sometimes accompany a renal transplant. Herein, we report a large granular lymphocyte (LGL) leukemia patient with pure red cell aplasia (PRCA) after renal transplantation. A 36-year-old female was presented to our department with anemia in February 1996.

Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes.

The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/-) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross-linking.

Differential clinical courses of pregnancies complicated by diabetes insipidus which does, or does not, pre-date the pregnancy.

We present six cases of diabetes insipidus (DI) complicating pregnancy. In three cases, DI was manifested during pregnancy and required the administration of desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP). All these cases exhibited abnormal laboratory data such as an elevation of liver enzymes or a decrease in serum antithrombin III.

Evidence for an elevation in serum interleukin-2 and tumor necrosis factor-alpha levels before the clinical manifestations of preeclampsia.

Problem: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia.

Method Of Study: The serum concentrations of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) were determined by using enzyme-linked immunoadsorbent assay (ELISA) in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy (preeclamptic group) and in women who completed pregnancy uneventfully (control group).

Results: Serum concentrations of both IL-2 and TNF-alpha in the first trimester of the preeclamptic group were significantly higher than those of the control group.

Brca2 is required for embryonic cellular proliferation in the mouse.

Mutations of the tumor suppressor gene BRCA2 are associated with predisposition to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of the Brca2 gene were deleted by gene targeting (Brca2(10-11)) die before day 9.5 of embryogenesis.

Oscillation of ADP-ribosyl cyclase activity during the cell cycle and function of cyclic ADP-ribose in a unicellular organism, Euglena gracilis.

In Euglena gracilis, the activity of ADP-ribosyl cyclase, which produces cyclic ADP-ribose, oscillated during the cell cycle in a synchronous culture induced by a light-dark cycle, and a marked increase in the activity was observed in the G2 phase. Similarly, the ADP-ribosyl cyclase activity rose extremely immediately before cell division started, when synchronous cell division was induced by adding cobalamin (which is an essential growth factor and participates in DNA synthesis in this organism) to its deficient culture. Further, cADPR in these cells showed a maximum level immediately before cell division started.

Developmental sequence of human fetal body movements in the second half of pregnancy.

To describe fetal body movements precisely and to clarify their developmental sequence in the second half of pregnancy, fetal body movements were observed in 31 normal fetuses between 20 and 41 weeks of pregnancy by using multiple ultrasonic machines. All movements of the whole trunk were able to be classified into six fundamental movements: flexion, stretch, rolling, startle, stepping, and writhing. Startle was always observed as a single movement, but others were more frequently observed as a part of combination rather than as a single movements.

Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3.

Distinct and evolutionarily conserved signal transduction cascades mediate survival or death in response to developmental and environmental cues. The stress-activated protein kinases, or Jun N-terminal kinases (SAPKs/JNKs), are activated in response to a variety of cellular stresses such as changes in osmolarity and metabolism, DNA damage, heat shock, ischaemia, or inflammatory cytokines. Sek1 (JNKK/MKK4) is a direct activator of SAPKs/JNKs in response to environmental stresses or mitogenic factors.