Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During mid-1988 in Zambia, a baseline survey of 388 households in Choma District in the Southern Province was conducted to collect data on immunization coverage among children 12-23 years old, diarrhea morbidity among children younger than 5, use of oral rehydration among these children, and nutritional status among children 24-59 months old. 75% of children were completely immunized against BCG, polio, diphtheria-pertussis-tetanus, and measles and had an immunization card compared to 36% for rural Zambia in 1986. Immunization coverage ranged from 79% for measles to 95% for BCG. The rural health centers (RHCs) reported 38 patients with measles, suggesting either that some children did not fully benefit from the immunization program or problems existed with the cold chain. Fluctuation in the DPT and polio vaccine supply resulted in a dropout rate of 12% between 1st and 3rd dose and 9% between 1st and 2nd dose, respectively, compared to 38% and 31%, respectively, for rural Zambia (1986). 22% of children had had a recent episode of diarrhea. The 2-week diarrhea incidence rate was 0.16 (assuming the diarrhea episode lasted 6 days). The annual diarrhea incidence rate stood at 4.8 episodes/child. 52% of children who had had a diarrheal episode used oral rehydration solution obtained from an RHC or a community health worker. 15% ingested home-made sugar/salt solution. 81% of mothers would first take their child with diarrhea to an RHC. Only 10% of households had access to potable water from a borehole. Leading water sources were shallow water holes (32%), dug wells (25%), and rivers (16%). The water supply evaporated during the dry season for 50% of households. Dumping feces in the bush (67%) and use of a pit latrine (30%) were the main methods of feces disposal. After the harvest, 38% of children 12-23 months old and 74% of those 24-59 months old were well-nourished. A health education program on safe water supplies and better sanitation and an intersectoral agriculture and health program are needed to control diarrhea and to fight malnutrition, respectively.
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PMID:A primary health care baseline survey in a rural district in Zambia. 762 3

This paper reports the solution conformation of a peptide (P196-267) derived from the calmodulin-binding domain of Bordetella pertussis adenylate cyclase. P196-267 corresponding to the protein fragment situated between amino acid residues 196-267 was overproduced by a recombinant Escherichia coli strain. Its affinity for calmodulin is only one order of magnitude lower (Kd = 2.4 nM) than that of the whole bacterial enzyme (Kd = 0.2 nM). The proton resonances of the NMR spectra of P196-267 were assigned using homonuclear two-dimensional techniques (double-quantum-filtered J-correlated spectroscopy, total correlation spectroscopy, and nuclear Overhauser enhancement spectroscopy) and a standard assignment procedure. Analysis of the nuclear Overhauser effect connectivities and the secondary shift distribution of C alpha protons along the sequence allowed us to identify the elements of regular secondary structure. The peptide is flexible in solution, being in equilibrium between random coil and helical structures. Two segments of 11 amino acids (situated between V215 and A225) and 15 amino acids (situated between L233 and A247) populate in a significant proportion the helix conformational state. The two helices can be considerably stabilized in a mixed solvent, trifluoroethanol/water (30/70), suggesting that the corresponding fragment in the intact protein assumes a similar secondary conformation. No elements of tertiary structure organization were detected by the present experiments. The conformational properties of the isolated calmodulin target fragment are discussed in relation with the available NMR and X-ray data on various peptides complexed to calmodulin.
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PMID:Structural characterization by nuclear magnetic resonance spectroscopy of a genetically engineered high-affinity calmodulin-binding peptide derived from Bordetella pertussis adenylate cyclase. 762 28

The role of inhibitory G-proteins and cyclic AMP in spinal mechanisms of kappa opioid receptor-mediated antinociception was assayed by recording the withdrawal response latency of the rat tail following immersion into a water bath of 49 degrees C. Intrathecal administration of pertussis toxin (1 microgram/rat, five days before the behavioral evaluation) prevented the antinociceptive effect of the kappa receptor agonist U-50,488H, while administration of dibutyryl cyclic AMP (10 micrograms/rat, 17 min. after U-50,488H) did not antagonize the antinociceptive action of the kappa ligand. Results suggest that in the spinal cord the signal transduction mechanism subserving the antinociceptive effect of U-50,488H involves a Gi or Go protein, but also that cyclic AMP is not implicated in coupling Gi/Go proteins to the effector system.
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PMID:Intrathecal pertussis toxin but not cyclic AMP blocks kappa opioid-induced antinociception in rat. 762 10

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

The immunogenic efficacy of multiple antigen peptides, MAPs, i.e. branched molecules in which multiple copies of a given immunogenic peptide are attached on a scaffold of lysine residues via both alpha and epsilon linkages, has been repeatedly demonstrated, but little is known about the structural arrangement of these peptide constructs. A conformational characterization was therefore performed for a known T cell epitope of the S1 subunit of Pertussis toxin, whose sequence is predicted to form alpha-helix. The peptide DNVLDHLTGR, its N-acetylated and C-amidated analogue and a tetrabranched MAP based on the N-acetylated peptide were prepared and studied by CD and two-dimensional 1H-NMR. No evidence of helical structure was obtained in water for the isolated peptides. In contrast, in triflouroethanol, the isolated epitopes fold into a helical structure spanning the segment Val3-Thr8 in the uncapped molecule and encompassing also the N-terminal region in the capped analogue. The mobile C-terminal region tends to adopt a distorted turn arrangement in both peptides due to the folding of Arg10 guanidinium over the backbone. No distortion of the helix structure was observed for the single-copy epitope in the four-branched MAP molecule in trifluoroethanol: each peptide chain is equivalent within the MAP and shows an even more regular helical pattern than the isolated end-blocked sequence. A slight difference was located at the junction with the lysine scaffold: the peptide bond to epsilon NH was found in a much more extended conformation than the corresponding link to alpha NH. These structural results correlate with in vitro T cell stimulatory activity of the three compounds examined and provide arguments supporting the previous suggestion that MAP tetramers are unlikely to elicit an immune response specific for the synthetic template assembly, a feature necessary to retain the advantage of the polymeric epitope presentation.
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PMID:Conformational study of a short Pertussis toxin T cell epitope incorporated in a multiple antigen peptide template by CD and two-dimensional NMR. Analysis of the structural effects on the activity of synthetic immunogens. 769 60

Water and electrolyte transport in turtle urinary bladder closely resembles that present in the mammalian collecting tubule. Although cAMP is known to participate in the control of mucosal transport processes, the GTP-binding inhibitory Gi and stimulatory Gs proteins which link receptors on the cell surface to the adenylate cyclase system remain to be identified in this urinary epithelium. To this end, individual cells harvested from the mucosal surface of the turtle bladder were isolated using a discontinuous density Ficoll gradient. Examination by electron microscopy of the material from the different layers of the Ficoll gradient confirmed that bands II and III contained carbonic anhydrase-rich cells and granular cells, respectively. Identification of Gi and Gs in carbonic anhydrase-rich and granular cells was accomplished using pertussis (PT) and cholera toxins to promote [32P] ADP ribosylation of the proteins. Separation of Gi and Gs from other cell proteins was accomplished using polyacrylamide gel electrophoresis and autoradiography. Pretreatment of cells with 0.2% triton X-100 substantially magnified the ADP-ribosylation of Gi by PT. A doublet form of Gi was present in the 40-kD region and indicated heterogeneity of the PT substrate in granular and carbonic anhydrase-rich cells. Gs was observed as a single polypeptide at the 42-kD region in both cell types. A distinct 45-kD peptide not present in mammalian collecting tubule was identified by both toxins in granular cells and by cholera toxin in carbonic anhydrase-rich cells. In summary, this investigation identified and characterized Gi and Gs proteins in carbonic anhydrase-rich and granular cells from the mucosa of turtle urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of GTP-binding proteins in turtle urinary bladder epithelial cells. 770 Feb 19

Angiotensin II (Ang II) is an important regulator of proximal tubule salt and water reabsorption. Recent studies indicate that rabbit proximal tubule angiotensin II receptors are the type-1 (AT1R) subtype. We studied the effect of Ang II on proximal tubule receptor expression. Rabbits were treated with either angiotensin converting enzyme inhibitors or a low salt diet to modulate endogenous Ang II levels. In captopril-treated rabbits, liver and glomerular AT1R mRNA levels increased 242 +/- 125 and 141 +/- 60%, respectively (n = 6-7; P < 0.05), as determined by quantitative PCR. In contrast, proximal tubule AT1R mRNA levels decreased 40 +/- 11% (n = 6; P < 0.05). Binding of 125I Ang II to renal cortical basolateral membranes of captopril-treated rabbits decreased from 2.9 +/- 0.55 to 1.4 +/- 0.17 fmol/mg protein (n = 6; P < 0.025). In rabbits fed a sodium chloride-deficient diet for 4 wk, AT1R mRNA levels decreased 52 +/- 11% in liver and 43 +/- 7% in glomeruli (n = 4-5; P < 0.05), whereas they increased 141 +/- 85% (n = 5; P < 0.05) in proximal tubule. In basolateral membranes from rabbits on the sodium chloride-deficient diet, specific binding of 125I Ang II increased from 2.1 +/- 0.2 to 4.3 +/- 1.1 fmol/mg protein (n = 7; P < 0.05). To determine whether Ang II directly regulates expression of proximal tubule AT1 receptors, further studies were performed in cultured proximal tubule cells grown from microdissected S1 segments of rabbit proximal tubules and immortalized by transfection with a replication-defective SV40 vector. Incubation of these cells with Ang II (10(-11) to 10(-7) M) led to concentration-dependent increases in both AT1R mRNA levels and specific 125I Ang II binding. Pretreatment with pertussis toxin inhibited Ang II stimulation of AT1R mRNA. AT1R mRNA expression was decreased by either forskolin or a nonhydrolyzable cAMP analogue (dibutryl cAMP). Simultaneous Ang II administration overcame the inhibitory effect of forskolin but not dibutryl cAMP. These results indicate that proximal tubule AT1R expression is regulated by ambient Ang II levels, and Ang II increases AT1R mRNA at least in part by decreasing proximal tubule cAMP generation through a pertussis toxin-sensitive mechanism. Upregulation of proximal tubule AT1R by Ang II may be important in mediating enhanced proximal tubule sodium reabsorption in states of elevated systemic or intrarenal Ang II.
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PMID:Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal tubule. 773 68

Adenylate cyclase toxin (ACT), a virulence factor of Bordetella pertussis, acquires hemolytic and toxic activities after post-translational modification of the cyaA gene product, CyaA. The exact nature of this modification is unknown, but homology to the related repeat toxin alpha-hemolysin of Escherichia coli suggests that fatty acylation of a lysine residue may be involved. In the present study, we used an in vitro chemical approach to acylate unmodified, inactive adenylate cyclase protoxin by using a new water-soluble compound, acylpyrophosphate. We show that undirected transfer of lauric, myristic, or palmitic acid chains to the CyaA protoxin is able to confer both hemolytic and toxic activities to ACT. The chemically modified protoxin shows a specific requirement for Ca2+ ions for toxic activity, as does the wild type toxin. However, the toxic and hemolytic activities of chemically modified ACT are low in comparison to ACT modified in vivo, suggesting that in vitro fatty acylation of the protoxin involves random modification of nucleophilic residues present in the toxin in contrast to the in vivo modification of specific sites.
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PMID:Chemical fatty acylation confers hemolytic and toxic activities to adenylate cyclase protoxin of Bordetella pertussis. 780 9

We have documented new observations with respect to PGE2 action in the rabbit CCD. (1) PGE2 can inhibit both cAMP and vasopressin-induced water flow, depending on the sequence of PGE2 addition with respect to vasopressin or cAMP. (2) PGE2 inhibition of vasopressin or cAMP-stimulated water flow can be reversed with staurosporine. Thus, PGE2 inhibits vasopressin-stimulated water flow by activation of PKC and (3) PGE2 induces release of calcium from intracellular stores. These results strongly suggest the presence of a PGE2 receptor coupled to PIP2 hydrolysis. PGE2 mediated increases in cytosolic calcium are responsible for the inhibitory action of PGE2 on sodium transport. While stimulation of cAMP production by PGE2 may contribute to the inhibition of sodium transport, it is not required since in the presence of 8-CPTcAMP, PGE2 still decreases sodium transport. The effect of PGE2 on sodium transport is pertussis toxin insensitive and is unlikely to be mediated by an inhibitory G protein. Using PGE2 and one of its selective analogues, sulprostone, we have provided evidence for functionally distinct PGE2 receptors. Separate PGE2 receptor subtypes appear to be coupled to separate transport processes. These receptor subtypes may correspond to the EP1, EP2 and EP3 receptors described earlier in smooth muscle. Thus, an EP2 like receptor stimulates cAMP generation and water reabsorption while an EP1 like receptor increases [Ca++]i and inhibits sodium reabsorption. Finally, an EP3 receptor, equivalently activated by sulprostone and PGE2, may couple to Gi and mediate pertussis toxin sensitive inhibition of vasopressin-stimulated water flow.
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PMID:Cellular signalling of PGE2 and its selective receptor analogue sulprostone in rabbit cortical collecting duct. 782 28

Emerging infectious diseases such as prolonged diarrheal illness due to water-borne Cryptosporidium, hemorrhagic colitis and renal failure from food-borne E. coli O157:H7, and rodent-borne hantavirus pulmonary syndrome as well as reemerging infections such as tuberculosis, pertussis, and cholera vividly illustrate that we remain highly vulnerable to the microorganisms with which we share our environment. Prompt detection of new and resurgent infectious disease threats depends on careful monitoring by modern surveillance systems. This article focuses on five important elements of improved surveillance for emerging infections: 1) strengthening the national notifiable disease system, 2) establishing sentinel surveillance networks, 3) establishing population-based emerging infections programs, 4) developing a system for enhanced global surveillance, and 5) applying new tools and novel approaches to surveillance.
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PMID:Emerging infectious diseases in the United States, Improved surveillance, a requisite for prevention. 784 Apr 68


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