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Background: Lower respiratory tract infections (LRTIs) are a cause of inpatient and outpatient care among children. Although orofacial clefts seem to be associated with LRTIs, epidemiological studies are scarce on this topic. This study aimed to examine whether infants with orofacial clefts were associated with LRTIs. Methods: This prospective cohort study used data from the Japan Environment and Children’s Study, for which baseline recruitment was conducted during 2011–2014. This study included 81,535 participants. The number of infants with cleft lip and palate (CLP), cleft lip (CL), and cleft palate only (CP) was 67, 49, and 36, respectively. We defined history of LRTIs until 12 months’ age reported by their mothers as the dependent variable. Accumulated breastfeeding duration was used as a potential mediator. Results: The incidence proportion of LRTIs among the control group was 6.0%. The incidence proportion among infants with CLP, CL, and CP were 11.9%, 14.3%, and 5.6%, respectively. After adjusting for covariates, compared with the control group, infants with CLP and CL were associated with risk of LRTIs (incidence risk ratio [IRR] of CLP, 2.38; 95% confidence interval [CI], 1.30–4.36 and IRR of CL, 2.73; 95% CI, 1.40–5.33), but not ones with CP (IRR 1.08; 95% CI, 0.28–4.15). Accumulated breastfeeding duration decreased the IRR of CLP only (IRR of CLP, 2.16; 95% CI, 1.19–3.93). Conclusion: Infants with orofacial clefts aged 1 year have a potentially high incidence proportion of LRTIs. Accumulated breastfeeding duration might mediate the associations of CLP.

Abstract Background Hereditary folate malabsorption—a rare disorder caused by impairment of the folate transporter—can develop into severe folate deficiency manifesting as megaloblastic anemia and occasionally thrombocytopenia. Reportedly, megaloblastic anemia can manifest with hemorrhagic episodes, possibly due to ineffective platelet production and platelet dysfunction. However, life-threatening hemorrhage events in hereditary folate malabsorption have not been well investigated. Case presentation A 3-month-old Japanese boy was transferred to our hospital due to thrombocytopenia and severe megaloblastic anemia. During a thorough examination of hematopoietic abnormalities, the patient suddenly went into cardiac arrest due to pulmonary hemorrhage. Although intravenous folate supplementation was started soon after the identification of folate deficiency, the patient died of circulatory defect and multiple organ failure. The cause of pulmonary hemorrhage, such as respiratory infection, could not be confirmed. Genetic investigation revealed a mutation in the SLC46A1 gene to be the cause of the hereditary folate malabsorption. Conclusion We report an infantile case of hereditary folate malabsorption that progressed to lethal pulmonary hemorrhage before folate deficiency was identified. Clinicians should consider that megaloblastic anemia could lead to severe bleeding without warning, and that nutrient supplementation should be initiated as soon as possible.

Hemoglobin (Hb) is the most abundant protein in blood, with concentration of about 12–15 g/dl. The highly concentrated Hb solution (35 g/dl) is compartmentalized in red blood cells (RBCs). Once Hb is released from RBCs by hemolysis during blood circulation, it induces renal and cardiovascular toxicities. To date, hemoglobin-based oxygen carriers of various types have been developed as blood substitutes to mitigate the Hb toxicities. One method is Hb encapsulation in phospholipid vesicles (liposomes). Although the Hb toxicity can be shielded, it is equally important to ensure the biocompatibility of the liposomal membrane. We have developed Hb-vesicles (HbV). A new encapsulation method using a rotation-revolution mixer which enabled efficient production of HbV with a high yield has considerably facilitated R&D of HbV. Along with our academic consortium, we have studied the preclinical safety and efficacy of HbV extensively as a transfusion alternative, and finally conducted a phase I clinical trial. Moreover, carbonyl-HbV and met-HbV are developed respectively for an anti-inflammatory and anti-oxidative agent and an antidote for poisons. This review paper specifically presents past trials of liposome encapsulated Hb, biocompatible lipid bilayer membranes, and efficient HbV preparation methods, in addition to potential clinical applications of HbV based on results of our in vivo studies.

Hypertrophic cardiomyopathy (HCM) is the primary cause of sudden cardiac death in children and adolescents. Patients with HCM frequently have ventricular tachycardia and ventricular fibrillation, although complete atrioventricular block (CAVB) is very rare. We report a case of HCM with CAVB in an 8-year-old girl who underwent transvenous implantable cardioverter-defibrillator placement after resuscitation. In this patient, we identified a de novo heterozygous missense variant, Arg406Trp (c.1216C > T), in the desmin (DES) gene. Pathogenic variants in the DES gene result in cardiomyopathy, conduction disorders, and skeletal muscle weakness. This recently identified variant may cause HCM with CAVB. Résumé: La cardiomyopathie hypertrophique (CMH) est la première cause de mort subite d'origine cardiaque chez les enfants et les adolescents. Les patients atteints de CMH présentent fréquemment une tachycardie ventriculaire et une fibrillation ventriculaire, bien que le bloc auriculo-ventriculaire complet (BAVC) soit très rare. Nous rapportons un cas de CMH avec BAVC chez une fillette de 8 ans qui a reçu un défibrillateur cardioverteur implantable par voie transveineuse après réanimation. Chez cette patiente, nous avons isolé un variant faux sens hétérozygote de novo, Arg406Trp (c.1216C > T), dans le gène de la desmine (DES). Les variants pathogènes du gène DES entraînent une cardiomyopathie, des troubles de la conduction et une faiblesse des muscles squelettiques. Ce variant récemment identifié peut causer une CMH avec BAVC.

Abstract Background The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD. Methods We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD. Results A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050). Conclusions The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.

Background: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL±P) and cleft palate only (CP) in Japan. Methods: We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (

BackgroundThe influence of mothers' and fathers' educational levels in separate evaluations of asthma has not been fully investigated. This study aims to examine the associations of the mother's and fathers' educational levels with childhood wheeze and asthma adjusting for crude and pre-and post-natal modifiable risk factors.MethodsWe conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. The mother's and father's educational levels were surveyed by a questionnaire during the pregnancy, and childhood wheezing and doctor-diagnosed asthma were estimated using a 3-year questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between the mother's and father's educational levels and childhood wheezing and asthma, adjusted for pre-and post-natal factors.ResultsA total of 69,607 pairs of parents and their single infants were analyzed. We found 17.3% of children had wheezing and 7.7% had asthma. In crude analyses, lower educational level of parents was associated with an increased risk of childhood wheezing and asthma. After full adjustment, a lower educational level of mothers was associated with an increased risk of childhood asthma (junior high school (reference: high school); odds ratio (OR): 1.17, 95% CI, 1.01-1.36), and higher educational level, especially the mother's, was associated with an increased risk of childhood wheezing (technical junior college, technical/vocational college, or associate degree (ECD3); OR: 1.12, 95% CI, 1.06-1.18, bachelor's degree, or postgraduate degree; OR: 1.10, 95% CI, 1.03-1.18), and asthma (ECD3; OR: 1.13, 95% CI, 1.04-1.21).ConclusionsParents' lower educational level was a crude risk factor for childhood wheezing and asthma. However, an increased risk of wheezing due to mothers' higher educational level was found after adjusting for pre-and post-natal factors.

Inflammatory bowel disease (IBD) is initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Here, the authors show that inhibition of the calreticulin binding to integrin α subunits ameliorates the severity of IBD in animal models.

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.

Abstract Background Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis. Case presentation We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring. Conclusions These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications.

Introduction: Moyamoya disease (MMD) is characterized by progressive stenosis and occlusion in the terminal portion of both internal carotid arteries (ICAs) and the formation of an abnormal vascular network. Because of the fragile structure of the collateral vessels, MMD is frequently accompanied by intracranial aneurysms that are mainly located within the abnormal basal network or the circle of Willis. However, the association between MMD and aneurysms of the ICAs has never been reported previously. Case report: A 1-month-old infant presented with a decreased level of consciousness and arterial infarction in the right frontal and temporal lobes. Brain computed tomography angiography results showed aneurysms in both ICAs and occlusions of the distal part of the aneurysms without moyamoya collateral vessels. Aspirin therapy was initiated, and his clinical status stabilized. At 12 months of age, collateral networks of small vessels were found in the distal part of both ICAs, and MMD had evolved. At 24 months of age, he remains on aspirin therapy, and no further ischemic events have occurred. Conclusions: This is the first report of MMD in which ICA aneurysms and occlusions developed bilaterally in early infancy without moyamoya collateral vessels. Our case indicates that angiogenesis at the base of the brain may occur following extracellular matrix remodeling at the terminal portion of the ICAs.

Asplenia syndrome is frequently complicated by a total anomalous pulmonary venous connection. Pulmonary venous obstruction, following total anomalous pulmonary venous connection surgery, is one of the risk factors for morbidity and mortality. In some patients, the pulmonary vasculature is abnormal even in the absence of clinical evidence of pulmonary venous obstruction. We hypothesized that a change in the pulmonary hemodynamics could indicate the abnormality of pulmonary vein in a patient with asplenia, single right ventricle, and total anomalous pulmonary venous connection, following Fontan procedure. Here, we present a case of asplenia, single right ventricle, total anomalous pulmonary venous connection, and right pulmonary venous obstruction in which evidence of a potential left pulmonary venous obstruction was obtained following the administration of inhaled nitric oxide and oxygen.

Juvenile-onset systemic sclerosis (jSSc) is a rare condition, having unique characteristic features compared to adult-onset SSc. Although cardiac involvement (CI) is known as a leading cause of mortality overall in SSc, the importance of CI in jSSc has not been emphasized. Here we present a 13-year-old female with jSSc overlapped with dermatomyositis (DM) complicated CI. She developed skin thickness and induration, Raynaud’s phenomenon, digital pitting scars in fingertips, and skeletal myositis. Oral prednisolone and pulse methotrexate treatment led to the improvement of skin findings; however two weeks after the initiation she suddenly presented with muscle pain and dyspnea within a few days. Cardiac investigations then showed pericardiac effusion and diastolic dysfunction due to significant biventricular hypertrophy causing heart failure. As pericardiac effusion and exacerbation of skeletal myositis were evident, steroid pulse therapy was initiated. Unexpectedly, not only the myositis but also the CI including diastolic dysfunction was improved. She thereafter followed a favorable clinical course without reactivation of the CI or cardiac fibrosis. As a conclusion, close attention to CI must be paid in jSSc patients, especially when skeletal muscle involvement is evident and immunosuppressive therapy may be effective for CI in jSSc in cases where it occurs abruptly.

Eyelid myoclonia with absences is classified as a unique type of generalized seizure. Its pathogenesis is proposed to involve the functional abnormalities in cortical–subcortical networks. Here, we describe the case of a 7-year-old boy who had eyelid myoclonia with absences, along with focal motor seizures. Video-EEG monitoring demonstrated eyelid myoclonia associated with 4- to 5-Hz generalized polyspike–waves preceded by focal frontal discharges. Interictal EEG showed focal epileptiform discharges over the frontal regions. Our case suggests an important role of the frontal lobe in the generation of eyelid myoclonia with absences.

In the present experiments, we tried to elucidate whether changes in arginase activity and protein expression of arginase I and II are involved in the occurrence of intimal hyperplasia in premenopausal human uterine arteries. They were obtained from thirty-four patients undergoing total abdominal hysterectomy with informed consent for the present study. All specimens were assessed histologically and the intima/media ratio (%) was evaluated as an index of the intimal hyperplasia. Thirteen patients out of 34 had histologically normal arteries (intima/media ratio = 18.1 ± 0.7%), whereas the remaining 21 patients had various degrees of intimal hyperplasia (intima/media ratio = 32.7 ± 2.3%), and these specimens were categorized as hyperplasic. Intimal hyperplasia was accompanied by impaired cyclic GMP production, enhanced overall arginase activity, and up-regulations of arginase I and II in endothelial cells and of arginase II in the smooth muscle layer. Pearson’s correlation coefficient analyses revealed the close relationships among the arginase activities in endothelial cells and smooth muscle layer, the intimal /media ratio, and cyclic GMP production. These results suggest that the enhanced arginase activity and expressions of two arginase subtypes shed new light on the processes associated with the occurrence of intimal hyperplasia in premenopausal human uterine arteries. Keywords:: intimal hyperplasia, arginase I and II, cyclic GMP, nitric oxide, human uterine artery

We examined the involvement of nitric oxide (NO) and/or endothelium-derived hyperpolarizing factor (EDHF) in decreasing peripheral vascular resistance in the rat hind limb perfusion model and analyzed the identity of EDHF in this model. The potency of carbachol (CCh) to produce relaxation was quantitatively similar to sodium nitroprusside (SNP). CCh-induced relaxation was abolished after endothelial denudation, but resistant to nitroarginine and indomethacin. The relaxation was inhibited by tetraethylammonium, ouabain, charybdotoxin plus apamin, and under depolarization. SNP-induced relaxation was accompanied by increased cGMP production, which was inhibited by ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one). Although CCh produced a similar extent of relaxation to SNP, the cGMP level was 24 times lower than that with SNP. Low KCl produced a definite relaxation, which was inhibited by ouabain, but independent of NO, prostacyclin, and endothelium. 1-EBIO (1-ethyl-2-benzimidazolinone) as an activator of IKCa channel also produced a concentration-dependent relaxation, which was inhibited by charybdotoxin, ouabain, and depolarization, but independent of NO and prostacyclin. Clotrimazole and 17-octadecynoic acid as inhibitors of P450 monooxygenase inhibited the CCh-induced relaxation. Meanwhile, catalase at a concentration sufficient to inhibit H2O2-induced relaxation did not exert definite inhibition of the CCh-induced relaxation. These results suggest that CCh produces an endothelium-dependent, EDHF-dependent, and NO-cGMP-independent relaxation and that K+ and metabolite(s) of P450 monooxygenase possibly play an important role for this relaxation. Keywords:: hind limb perfusion model, carbachol-induced relaxation, endothelium-derived hyperpolarizing factor, K+ ion, metabolite of P450 monooxygenase

Background: POU1F1 encodes both PIT-1a, which plays pivotal roles in pituitary development and GH, PRL and TSHB expression, and the alternatively spliced isoform PIT-1β, which contains an insertion of 26-amino acids (β-domain) in the transactivation domain of PIT-1a due to the use of an alternative splice acceptor at the end of the first intron. PIT-1β is expressed at much lower levels than PIT-1a and represses endogenous PIT-1a transcriptional activity. Although POU1F1 mutations lead to combined pituitary hormone deficiency (CPHD), no patients with β-domain mutations have been reported. Results: Here, we report that a three-generation family exhibited differe nt degrees of CPHD, including growth hormone deficiency with intrafamilial variability of prolactin/TSH insufficiency and unexpected prolactinoma occurrence. The CPHD was due to a novel POU1F1 heterozygous variant (c.143-69T>G) in intron 1 of PIT-1a (RefSeq number NM_000306) or as c.152T>G (p.Ile51Ser) in exon 2 of PIT-1β (NM_001122757). Gene splicing experiments showed that this mutation yielded the PIT-1β transcript without other transcripts. The lymphocyte PIT-1β mRNA expression was significantly higher in the patients with the heterozygous mutat ion than a control. A luciferase reporter assay revealed that the PIT-1β-Ile51Ser mutant repressed PIT-1a and abolished transactivation capacity for the rat prolactin p romoter in GH3 pituitary cells. Conclusions: We describe, for the first time, that the PIT-1 β mutation can cause CPHD through a novel genetic mechanism, such as PIT-1β overexpression, and that POU1F1 mutation might be associated with a prolactinoma. Analysis of new patients and long-term follow-up are needed to clarify the characteristics of PIT-1β mutations. [ABSTRACT FROM AUTHOR]

There are no recommended diagnostic criteria for transient congenital hypothyroidism (CH) during early childhood. In this study, we aimed to identify the factors that distinguish permanent (P)- and transient (T)-CH. We retrospectively analyzed the clinical, biochemical, and imaging data of 42 children with a definitive diagnosis of P- or T-CH by re-evaluation tests at our institution from November 1986 to October 2019. Patients who continued levothyroxine (L-T4) treatment after the re-evaluation tests were classified as group P (n = 19), while patients who were diagnosed with T-CH and discontinued L-T4 treatment were classified as group T (n = 23). Initial testing performed during infancy showed that the mean serum TSH and free T4 (FT4) levels did not differ significantly between groups P and T. None of the patients in group T required an increased dosage of L-T4 at the age of 3 yr and above while 85% of the patients in group P required increased dosages of L-T4. Hence, T-CH was suspected in patients who did not require an increase in L-T4 dosage at the age of 3 yr and above. [ABSTRACT FROM AUTHOR]

The European Union has approved a new energy strategy for 2030, the target being to save the 27% of primary energy compared with the business-as-usual scenario and to reduce the CO2 emission of 40%. Each member state shall establish an indicator showing the energy efficiency contribution towards the Member State's 2030 target. Under such challenging target, the use of optimized energy management system has the potential to greatly contribute to the reduction of both the primary energy and the CO2 emission. Of course, the economic benefit for installing these systems is also an important issue from owner's point of view, and it has a big influence on the technical solution choice. The energy management systems are capable to optimize the schedule of boilers, electric chillers, and other kind of generators. In this latter case, the use of cogeneration systems is often applied, in order to increase the overall efficiency of the plant, often in combination with absorption chillers to make effective use of the heat also with large cooling loads and small heating duties. The fuel sources of all these pieces of equipment are represented by natural gas and electricity, so the result of optimized operations is greatly modified depending on the situation of gas and electricity prices, which are strictly dependent on the country which the analysis is referred to. The purpose of this study is to clarify the influence of the electricity price and the natural gas price of each country on the optimum operation of an energy management system, considering the acquired energy demand pattern and the configuration of a multi-generation production plant consisting in a small Italian factory. The energy price scenarios which will be analyzed are related to 7 countries with large GDP in the EU region, on which optimization algorithm will be applied. The results will be focused on the comparison of the economic benefit, primary energy saving and reduction of CO2 emissions for each country, applying different target function of the optimizer (minimum running costs, primary energy consumption, or GHGs emissions), in order to highlight the most relevant parameters determining the benefit of the energy management system. [ABSTRACT FROM AUTHOR]

Hemoglobin vesicles (HbVs) are oxygen carriers consisting of Hb molecules and liposome in which human hemoglobin (Hb) molecules are encapsulated. Investigations of HbV biocompatibility have shown that HbVs have no significant effect on either the quality or quantity of blood components such as RBC, WBC, platelets, complements, or coagulation factors, reflecting its excellent biocompatibility. However, their effects on the immune system remain to be evaluated. HbVs might affect the function of macrophages because they accumulate in the reticuloendothelial system. Results show that splenic T cell proliferation is suppressed after injection of not only HbV but also empty liposome into rat, and show that macrophages that internalized liposomal particles are responsible for the suppression. However, the effect is transient. Antibody production is entirely unaffected. Further investigation revealed that those macrophages were similar to myeloid-derived suppressor cells (MDSCs) in terms of morphology, cell surface markers, and the immune-suppression mechanism. Considering that MDSCs appear in various pathological conditions, the appearance of MDSC-like cells might reflect the physiological immune system response against the substantial burden of liposomal microparticles. Therefore, despite the possible induction of immunosuppressive cells, HbVs are an acceptable and promising candidate for use as a blood substitute in a clinical setting. [ABSTRACT FROM AUTHOR]

Abstract  Based on colonoscopy findings, we made a preoperative diagnosis of primary mucinous cystadenocarcinoma of the appendix with features of a submucosal tumor (SMT) in the ascending colon. A 59-year-old woman who presented with right lower quadrant abdominal pain underwent colonoscopy, which revealed an SMT with three nodules covered with mucus in the ascending colon. Examination of colonoscopic biopsy specimens indicated “very” well-differentiated adenocarcinoma with mucus lakes. Abdominal computed tomography showed irregular wall thickness from the cecum to the ascending colon. The adjacent appendix had an enhanced wall and unclear border against the ascending colon. Thus, we performed right hemicolectomy, with good results. Histopathological examination revealed mucinous cystadenocarcinoma of the appendix, invading the ascending colon with fistula formation. Appendiceal tumors can manifest with a variety of colonoscopic features, and curative surgical resection should be attempted even if there is fistula formation. [ABSTRACT FROM AUTHOR]

Thrombopoietin (TPO) is a hematopoietic cytokine that regulates megakaryocytosis and thrombocytosis by binding to its receptor (c-Mpl). The signaling pathways downstream of c-Mpl include the Ras/Raf/MAP kinase and JAK/STAT pathway and are transduced into the regulation of immediate early-, early- and delayed-response genes. How these genes couple c-Mpl activation to the biochemical machinery of cell growth and cell cycle progression in hematopoietic cells is still unclear. UT-7/TPO is a recently characterized TPO-dependent cell line. Using RNA fingerprinting with arbitrarily primed PCR (RAP-PCR) to identify the TPO-regulated genes in this cell line, we found that the mRNA expression of nucleolin was upregulated in the UT-7/TPO cells in response to TPO. Concomitantly, the TPO-stimulated cells expressed an increased amount of full length nucleolin as determined by immunoblot analysis. The TPO-induced upregulation of nucleolin mRNA was not inhibited by the MEK1/2 inhibitor PD98059, suggesting that ERK/MAPK activation is not necessary for elevation of nucleolin gene expression in response to TPO in UT-7/TPO. Nucleolin is a multifunctional nucleolar protein thought to be involved in many cellular processes, including ribosome biogenesis, the processing of ribosomal RNA (rRNA), mRNA stability, transcriptional regulation, and cell proliferation. Thus, these results indicate that the upregulation of nucleolin mRNA and protein may be important for the TPO-induced effects of hematopoietic cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Histamine may have physiologic functions in the inner ear. The locations of histamine receptors, however, have not yet been identified in the mammalian cochlea. The aim of this study was to investigate the localization of histamine receptor subtypes (H1, H2, and H3 receptors) in rat cochlea.METHODS:: Immunohistochemistry was performed with antibodies specific for each of the histamine receptors (H1, H2, and H3). To identify the type I and II spiral ganglion cells in the cochlea, some cryostat sections were double stained with antibodies to both a histamine receptor and neurofilament 200 kD, which predominantly stains type II spiral ganglion cells in the cochlea.RESULTS:: All H1, H2, and H3 receptor immunoreactive staining was limited to the spiral ganglion cells of the cochlea. Spiral ganglion cells with positive immunoreactivity to the neurofilament 200 kD antibody were stained only slightly by histamine H1, H2, and H3 receptor antibodies, indicating that histamine receptor immunoreactivity is specific to type I ganglion cells.CONCLUSIONS:: These findings indicate that histamine receptors are present in the cochlea and support the hypothesis that histamine plays a physiologic role in the cochlea. [ABSTRACT FROM AUTHOR]

Objective Increased NO is proposed to be responsible for the decreased peripheral resistance during pregnancy. The involvement of endothelium-derived hyperpolarizing factor (EDHF) remains unclear. We examine the involvement of NO and EDHF in the decreased peripheral resistance during pregnancy of the rat. Methods The hind-leg perfusion models were prepared from nonpregnant and 20 days pregnant rats. Changes in perfusion pressure were recorded during the perfusion with the modified Krebs solution. Basal pressure, the phenylephrine-induced contraction (PIC), and relaxation responses to carbachol (CCh) under the PIC were determined. Pharmacological analyses of these parameters were performed using LNA as NOS inhibitor, indomethacin (IM), ODQ as a guanylate cyclase inhibitor, high[K[sup +]], and tetraethylamonium (TEA), charybdotoxin (CTX) and apamin (APM) as nonselective, large and small conductance Kca channel blockers, respectively. Results At 20 days pregnancy, the PIC was decreased, whereas the CCh-induced relaxation was enhanced. LNA, IM, APM and CTX alone or IM + LNA did not affect the CCh-induced relaxation whereas TEA, ODQ, APM + CTX and high[K[sup +]]inhibited it. Conclusion The endothelium-dependent CCh-induced relaxation in the peripheral resistant vessels was increased at the late pregnancy. The relaxation appears to be mediated by EDHF but not by NO. [ABSTRACT FROM AUTHOR]