Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neisseria meningitidis serogroup B infections are among the major causes of fulminant septicemia and meningitis, especially severe in young children, and no broad vaccine is available yet. Because of poor immunogenicity of the serogroup B capsule, many efforts are now devoted to the identification of protective protein antigens. Among those are PorA and, more recently, transferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidis was genetically fused to the N-terminal domain of the Bordetella pertussis filamentous hemagglutinin (FHA), and the fha-tbpB hybrid gene was expressed in B. pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the recombinant strains, despite its large size, and was recognized by both anti-FHA and anti-TbpB antibodies. A single intranasal administration of recombinant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (IgG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of the IgG1, IgG2a, and IgG2b isotypes and were found to express complement-mediated bactericidal activity against N. meningitidis. These observations indicate that recombinant B. pertussis may be a promising vector for the development of a mucosal vaccine against serogroup B meningococci.
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PMID:Production of Neisseria meningitidis transferrin-binding protein B by recombinant Bordetella pertussis. 1150 Apr 15

The Health Council of the Netherlands (Gezondheidsraad) assessed the vaccination of infants against both group-C meningococci and pneumococci in terms of general criteria and basic principles for inclusion in the national vaccination programme. Vaccination against meningococci C in the Netherlands is expected to prevent about 300 cases of meningococcal disease (meningitis or sepsis), 22 deaths and 12 cases of severe lasting problems (neurological problems or amputations) per year. Vaccination against pneumococci may prevent about 100 cases of meningitis or sepsis, 3200 cases of pneumonia, 36,000 cases of acute otitis media, 11 deaths, 11 cases of severe permanent damage (neurological problems, deafness) per year. The Health Council advised implementing vaccination against group-C meningococci as soon as possible, through 2 injections at the ages of 5 and 6 months or through 1 injection shortly after the child's first birthday, and to carry out a catch-up programme for all children and adolescents up to and including 18 years of age. The council also advised starting a vaccination programme against pneumococci, at ages 2, 3 and 4 months, as soon as the current vaccinations against diphtheria, tetanus, pertussis and polio and against Haemophilus influenzae type b are combined into 1 injection (in 2002 or 2003). In view of the concentration of pneumococci disease in the first years of life, a catch-up programme is not indicated in this case. The Health Council emphasised the importance of microbiological and clinical monitoring of potential adverse effects and of public education programmes. The cost of vaccination against group-C meningococci is comparable to that of other accepted programmes for primary prevention. Compared to other programmes and at the current vaccine price, the cost of vaccination against pneumococci is high.
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PMID:[Universal vaccination against group-C meningococci and pneumococci; summary of the advice from the Health Counsil of the Netherlands]. 1221 5

The spectacular decline of infant mortality in Costa Rica from 68/1000 live births in 1970 to 20/1000 in 1980 was largely due to the implementation of public health programs in the 1970s. The abrupt decline was even more notable because deaths of infants constituted the major health problem of the country during the 1960s, accounting for 40% of all registered deaths. Socioeconomic development and reduced fertility contributed to the reduction, but 3/4 of the improvement can be attributed to extension of primary health care to previously unserved rural populations and to better secondary health care, according to a study by the Costa Rican demographer Luis Rosero Bixby. The programs targeted at less privileged groups substantially reduced class and geographic differentials in infant mortality. Infant mortality began to decline at an accelerating rate in 1972, coinciding with the first national health plan and the law of universal social security in 1971, the transfer of public hospitals to the social security system and promulgation of a general health law in 1973, and application of the rural health program in 1973 and community health program in 1976. By 1980, home services reached 60% of the population and immunization programs were in place for measles and diphtheria, pertussis, and tetanus. There was a doubling of outpatient services and a tripling of hours contracted by doctors between 1970-80. Also in 1980, 78% of the Costa Rican population was fully covered by health insurance. After 1972, infant mortality declined from all causes except complications of pregnancy and congenital anomalies. The decline was most rapid for deaths due to prematurity, illnesses avoidable by vaccination, and illnesses such as septicemia and meningitis in which prompt diagnosis and treatment can be lifesaving. Although impressive gains were made in neonatal mortality, the main share of the decline between 1970-80 was in postneonatal mortality. Reductions in deaths due to diarrheal diseases and respiratory infections through sanitation measures and immunization accounted for 3/4 of infant mortality decline before 1972 and 1/2 the reduction afterwards. After 1972, the introduction of improvements in neonatology and prenatal care and improvements in family planning service deliver produced a gradual and constant decline in neonatal mortality. Rosero Bixby's application of correlation and multiple regression analysis to census and vital statistics data for Costa Rica's 79 counties indicated that 41% of the decline in infant mortality from 1972-80 could be attributed to extension of primary health care principally in rural areas, while 75% could be attributed to improvements in primary and secondary health care together. Socioeconomic progress contributed about 22% to the decline and reduced fertility about 5%. The analysis did not take into account fertility declines or socioeconomic progress achieved before the 1970s.
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PMID:[Public health programs have greatly reduced infant mortality in Costa Rica]. 1226 50

Children with sickle cell anemia are more exposed to infection than healthy children. Indeed, infections are the major cause of morbidity and mortality in children with sickle cell anemia, especially those aged 6 months to 5 years. Phagocytosis is reduced in these children. Polynuclear neutrophils reveal various poorly understood irregularities and are associated with a reduction of phagocytic power: zinc deficiency, reduced post-phagocytic oxidative metabolism, and a prevalence of neutrophils not forming red sheep-like globule carriers of immunoglobulin H. The power of the antibody which renders germs susceptible to phagocytosis in the serum is reduced in sickle cell patients. This may be tied to a disorder in the alternate complementary route with reduction of C3 and properdin. Sequestration of sickle cell-shaped red blood cells, splenic congestion, and short circuits of important functional territories contribute to spleen dysfunction, which occurs early. Common pathogens attacking sickle cell patients are pneumococci, salmonella species, and Haemophilus influenzae. They cause very grave infections (e.g., septicemia and purulent meningitis). Prevention of infections dwells on three perspectives: early screening for sickle cell anemia and for spleen dysfunction, preventive penicillin therapy, and vaccination. In Benin, vaccination is the only means to prevent infections. Essential vaccinations for children with sickle cell anemia include BCG, diphtheria-pertussis-tetanus, polio, and Rouvax. Strongly recommended vaccinations are Pneumovax 23, HEVAC B, TAB, vaccine against H. influenzae, and vaccine against mumps. A vaccine calendar for children with sickle cell anemia guides health workers when they must administer the vaccines and their boosters over a six year period. It is not yet universal in health facilities in Benin. A short- and long-term evaluation of the calendar's efficacy would allow one to appreciate its real impact on reducing morbidity and mortality in children with sickle cell anemia.
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PMID:[Prevention of infectious diseases in the drepanocytic child]. 1229 Jan 82

The Lady Dufferin Fund, founded in 1885 in India, had by 1940 established 400 hospitals to alleviate diseases and mortality related to childbirth. After independence 2328 community health centers and 21254 primary health centers were created in the country. During 1974-94 more than 131,000 subcenters were set up and about 620,000 auxiliary nurse midwives (ANMs) had been trained. The Ministry of Health introduced four health prevention schemes in 1969: 1) immunization of children against diphtheria, pertussis, and tetanus; 2) immunization of pregnant women against tetanus; 3) prophylaxis of mothers and children against nutritional anemia; and 4) prophylaxis of children against blindness caused by vitamin A deficiency. As a result, infant mortality declined from 146/1000 live births to 74/1000 in 1993; but maternal mortality still stayed around 4-5/1000. In 1993 an estimated 117,356 maternal deaths occurred out of a total of 26,057,000 births, equalling 4.5 deaths per 1000 live births. The main causes of maternal deaths are hemorrhage, anemia, abortion, toxemia, and puerperal sepsis. Only about 411 first referral units in community health centers are functioning properly. Prenatal care of mothers includes the administration of tetanus toxoid and iron-folic acid tablets. However, the prenatal coverage reached only about 50% of mothers; and the coverage was only 21.4% in Bihar, 23.8% in Nagaland, 29.3% in Rajasthan, and 29.6% in Uttar Pradesh. In these areas administrative inefficiency is widespread with nonavailability of essential drugs for malaria, infections, sepsis, dysentery, and colds. During 1992-93 the rate of hospital deliveries ranged from 6.1% in Nagaland to 88.4% in Kerala, with a national average of only 25.6%. 71% of deliveries in rural areas and 30% in urban areas were conducted by untrained assistants. Although there are 450 ANM training schools in the country, the level of training has deteriorated. The major causes of infant deaths are respiratory infections and diarrhea, responsible for 13.5% and 6.9% of mortality, respectively. Severe malnutrition and inadequate vaccination are other major causes of child deaths and morbidity.
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PMID:Maternal and child health in India: a critical review. 1229 Sep 61

The objective of this study was to determine whether the serum of patients with sepsis could alter the capability of healthy human peripheral blood mononuclear cells (PBMC) to synthesize cAMP in response to beta-adrenergic stimulation and to evaluate the involvement of the inhibitory pathway (Gi) of adenylyl cyclase in the sepsis-induced alteration of beta-adrenergic signaling. First, PBMC from a healthy donor were incubated for 24 h in serum-containing medium according to three culture conditions: serum alone, serum with pertussis toxin, and serum with propranolol. Second, PBMC were stimulated with 10(-5) M isoproterenol or 10(-6) M forskolin, and measurement of cyclic adenosine monophosphate (cAMP) intracellular accumulation was performed. Serum samples were obtained from three groups of subjects: 14 patients with severe sepsis, 21 patients with septic shock, and 10 healthy control subjects. Basal and forskolin-stimulated cAMP levels were similar in PBMC cultured in control or in septic serum. Isoproterenol-stimulated accumulation was reduced in PBMC preincubated in septic serum. The lowest cAMP levels were found after exposure to serum from patients with septic shock. The addition of pertussis toxin in the incubation medium constantly increased cAMP response to isoproterenol, but more significantly in PBMC exposed to septic serum. Incubation in the presence of propranolol had no significant effect. The serum of patients with sepsis contained soluble depressant substances that inhibited adenylyl cyclase activation by beta-adrenergic agonists. Septic shock serum exhibited the most potent inhibitory effect. Hyperactivation of the Gi pathway of adenylyl cyclase was mainly responsible for the altered transmembrane beta-adrenergic signaling.
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PMID:Impairment of beta-adrenergic signaling in healthy peripheral blood mononuclear cells exposed to serum from patients with septic shock: involvement of the inhibitory pathway of adenylyl cyclase stimulation. 1257 16

FTY720, a potent immunosuppressive agent, is phosphorylated in vivo into FTY720-P, a high affinity agonist for sphingosine 1-phosphate (S1P) receptors. The effects of FTY720 on vascular cells, a major target of S1P action, have not been addressed. We now report the metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P). Incubation of endothelial cells with FTY720 resulted in phosphorylation by sphingosine kinase activity and formation of FTY720-P. Sphingosine kinase-2 effectively phosphorylated FTY720 in the human embryonic kidney 293T heterologous expression system. FTY720-P treatment of endothelial cells stimulated extracellular signal-activated kinase and Akt phosphorylation and adherens junction assembly and promoted cell survival. The effects of FTY720-P were inhibited by pertussis toxin, suggesting the requirement for Gi-coupled S1P receptors. Indeed, transmonolayer permeability induced by vascular endothelial cell growth factor was potently reversed by FTY720-P. Furthermore, oral FTY720 administration in mice potently blocked VEGF-induced vascular permeability in vivo. These findings suggest that FTY720 or its analogs may find utility in the therapeutic regulation of vascular permeability, an important process in angiogenesis, inflammation, and pathological conditions such as sepsis, hypoxia, and solid tumor growth.
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PMID:Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. 1295 48

A neonate presenting to the emergency department can present a challenge to even the most experienced clinician. This article has focused on four deceiving and potentially devastating neonatal diseases. 1. Neonatal herpes is a potentially devastating illness without pathognomonic signs or symptoms. Early recognition and therapy can reduce mortality markedly. Although no specific sign or symptom is diagnostic,the diagnosis should be strongly considered in the presence of HSV risk factors, atypical sepsis, unexplained acute hepatitis, or focal seizure activity. Acyclovir therapy should be initiated before viral dissemination or significant CNS replication occurs. 2. Pertussis is a disease in which infants are at greatest risk of death or severe complication. Neonatal pertussis often presents in an atypical manner, lacking the classic signs and symptoms such as the "whoop."More common signs and symptoms include cough, feeding difficulty,low-grade fever, emesis, increasing respiratory distress, apnea, cyanosis,and seizures. Management should include hospitalization, supportive care, and antibiotics. 3. Congenital heart defects, particularly ductal-dependent lesions, may have an initial asymptomatic period that culminates in a rapidly progressive and fatal course. A neonate with CHD presents with shock refractory to volume resuscitation or pressor support. Resuscitative efforts are ineffective unless PGE, is administered. 4. Inborn errors of metabolism often are unsuspected because of their protean and heterogeneous nature. Signs and symptoms are subtle,are nonspecific, and often mimic other, more common diseases.An elevated index of suspicion, along with application and correct interpretation of a select few laboratory tests, is the key to making a diagnosis. Therapy is relatively straightforward and focused on resuscitation followed by prevention of catabolism and correction of specifically identified abnormalities. Although these disorders are relatively uncommon, prompt diagnosis and therapy can lead to a decrease in morbidity and mortality. The key is to maintain a high index of suspicion.
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PMID:Unsuspected neonatal killers in emergency medicine. 1547 77

Adrenomedullin (ADM) acts as an autocrine or a paracrine factor in the regulation of cardiac function. The intracellular mechanisms involved in the direct effect of ADM on adult rat ventricular myocytes (ARVMs) are still to be elucidated. In ARVMs from normal rats, ADM produced an initial (< 30 min) increase in cell shortening and Ca2+ transients and a marked decrease in both on prolonged incubation (> 1 h). Both effects were sensitive to ADM antagonist ADM-(22-52). Treatment with SQ-22536, an inhibitor of adenylate cyclase, blocked the positive inotropic effect of ADM and potentiated its negative inotropic effect. The negative inotropic effect was sensitive to inhibition by pertussis toxin (PTX), an inhibitor of Gi proteins and KT-5720, an inhibitor of PKA. The observations suggest a switch from Gs-coupled to PTX-sensitive, PKA-dependent Gi coupling by ADM in ARVMs. The ADM-mediated Gi-signaling system involves cAMP-dependent pathways because SQ-22536 further increased the negative inotropic actions of ADM. Also, because ADM is overproduced by ARVMs in our rat model of septic shock, ARVMs from LPS-treated rats were subjected to treatment with ADM-(22-52) and PTX. The decrease in cell shortening and Ca2+ transients in LPS-treated ARVMs could be reversed back with ADM-(22-52) and PTX. This indicates that ADM plays a role in mediating the negative inotropic effect in LPS-treated ARVM through the activation of Gi signaling. This study delineates the intracellular pathways involved in ADM-mediated direct inotropic effects on ARVMs and also suggests a role of ADM in sepsis.
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PMID:Gs and Gi coupling of adrenomedullin in adult rat ventricular myocytes. 1632 20

We previously showed that lysozyme (Lzm-S), derived from leukocytes, caused myocardial depression in canine sepsis by binding to the endocardial endothelium to release nitric oxide (NO). NO then diffuses to adjacent myocytes to activate the cGMP pathway. In a canine right ventricular trabecular (RVT) preparation, Lzm-S also decreased the inotropic response to field stimulation (FSR) during which the sympathetic and parasympathetic nerves were simulated to measure the adrenergic response. In the present study, we determined whether the pathway by which Lzm-S decreased FSR was different from the pathway by which Lzm-S reduced steady-state (SS) contraction. Furthermore, we determined whether the decrease in FSR was due to a decrease in sympathetic stimulation or enhanced parasympathetic signaling. In the RVT preparation, we found that the inhibitory effect of Lzm-S on FSR was prevented by NO synthase (NOS) inhibitors. A cGMP inhibitor also blocked the depressant activity of Lzm-S. However, in contrast to the Lzm-S-induced decline in SS contraction, chemical removal of the endocardial endothelium by Triton X-100 to eliminate endothelial NO release did not prevent the decrease in FSR. An inhibitory G protein was involved in the effect of Lzm-S, since FSR could be restored by treatment with pertussis toxin. Atropine prevented the Lzm-S-induced decline in FSR, whereas beta(1)- and beta(2)-adrenoceptor function was not impaired by Lzm-S. These results indicate that the Lzm-S-induced decrease in FSR results from a nonendothelial release of NO. NO then acts through inhibitory G protein to enhance parasympathetic signaling.
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PMID:Lysozyme, a mediator of sepsis, impairs the cardiac neural adrenergic response by nonendothelial release of NO and inhibitory G protein signaling. 1776 78


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