ライフサイエンスコーパス: HGE

1 HGE agent infection in immunocompromised mice progresses

2 HGE agent was demonstrated in mature and immature myeloi

3 HGE agent-infected C3H/HeJ mice were necropsied over 21

4 HGE binding, internalization, and proliferation were com

5 HGE infection of HL60 cells, bone marrow progenitors, gr

6 HGE should be added to the list of infections potentiall

7 HGE-agent infection of mice induces pathologic changes s

8 Sera from 20 HGE patients with indirect fluorescent-antibody (IFA) ti

9 Thirty-three of 38 HGE patient serum samples (87%), previously confirmed by

10 Although the North American HGE sequences showed the highest conservation (>98.1% id

11 This suggests that rP44 is an HGE-E. equi group-specific antigen.

12 romyscus leucopus mice were infected with an HGE agent.

13 lity among serologic tests using E. equi and HGE agent isolates for diagnosis of HGE will occasionall

14 y be useful in discriminating dually HME and HGE IFA-reactive sera.

15 specific serodiagnostic antigens for HME and HGE, respectively, could be used to discriminate IFA dua

16 urface protein 2 (MSP-2) in A. marginale and HGE and OMP-1 in E. chaffeensis.

17 even HGE patient serum samples, a horse anti-HGE serum, and a horse anti-Ehrlichia equi serum recogni

18 eroxidase-positive granules were seen around HGE agent inclusions but not around E. chaffeensis inclu

19 expression, as well as their ability to bind HGE and become infected.

20 idase treatment of HL60 cells prevented both HGE binding and infection.

21 only these rare CD15s-expressing cells bound HGE and became infected.

22 or, early endosomal antigen 1, and rab5, but HGE agent inclusions were not.

23 , Fuc-TVII, allowed binding and infection by HGE.

24 Human gingival epithelial cells (HGE) express two antimicrobial peptides of the beta-defe

25 les from 28 patients with well-characterized HGE and 9 patients with suspected HGE who were investiga

26 mens from 17 patients with culture-confirmed HGE also tested by IFA by using either a human isolate f

27 ummary, most patients with culture-confirmed HGE develop antibodies within 2 weeks of onset of sympto

28 samples from persons with culture-confirmed HGE or patients with Lyme disease and antibodies to the

29 ssay results for sera from culture-confirmed HGE patients, WB was used to confirm the specificity of

30 14 to 44% of acute-phase sera from confirmed HGE patients.

31 The incidence of confirmed HGE was 31 cases/100,000 in 1997, 51 cases/100,000 in 19

32 Vacuoles containing HGE bacteria incorporated endocytosed colloidal gold par

33 in neutrophils: morulae (vacuoles containing HGE organisms) are evident in polymorphonuclear leukocyt

34 In contrast, HGE agent in THP-1 or HL-60 cells induced no increase in

35 cted C3H mice, in SCID mice, and in cultured HGE bacteria.

36 he substrate in immunoblots to help diagnose HGE.

37 philum, the human granulocytic ehrlichiosis (HGE) agent and a variant (AP-Variant 1) that has not bee

38 SG3) of the human granulocytic ehrlichiosis (HGE) agent has identified a number of immunoreactive pro

39 vitro-grown human granulocytic ehrlichiosis (HGE) agent in horses.

40 The human granulocytic ehrlichiosis (HGE) agent in infected blood specimens remained viable d

41 tein of the human granulocytic ehrlichiosis (HGE) agent is an immunodominant antigen in human infecti

42 es, and the human granulocytic ehrlichiosis (HGE) agent is an obligatory intracellular bacterium of g

43 unties, and human granulocytic ehrlichiosis (HGE) agent isolates were obtained from Humboldt county.

44 The human granulocytic ehrlichiosis (HGE) agent resides and multiplies exclusively in cytopla

45 DNA of the human granulocytic ehrlichiosis (HGE) agent was detected in 17 of 47 mice (36.2%), but on

46 The human granulocytic ehrlichiosis (HGE) agent, which replicates in neutrophils, was found n

47 MPs) of the human granulocytic ehrlichiosis (HGE) agent, with molecular sizes of 44 to 47 kDa, are im

48 tive to the human granulocytic ehrlichiosis (HGE) agent.

49 he agent of human granulocytic ehrlichiosis (HGE) amplified DNA from extracts of these cells.

50 etection of human granulocytic ehrlichiosis (HGE) and determination of etiology when serologic testin

51 disease and human granulocytic ehrlichiosis (HGE) are tick-borne illnesses caused by Borrelia burgdor

52 d of having human granulocytic ehrlichiosis (HGE) but who lacked antibodies to ehrlichiae revealed Ig

53 he agent of human granulocytic ehrlichiosis (HGE) codes for a protein with a predicted molecular size

54 tients with human granulocytic ehrlichiosis (HGE) commonly recognize a 44-kDa antigen.

55 atient with human granulocytic ehrlichiosis (HGE) developed anemia and leukopenia, but by day 24, the

56 ncidence of human granulocytic ehrlichiosis (HGE) in the upper Midwest is uncertain.

57 Human granulocytic ehrlichiosis (HGE) is a febrile tick-borne illness caused by a recentl

58 he agent of human granulocytic ehrlichiosis (HGE) is a newly recognized tick-borne pathogen that resi

59 Human granulocytic ehrlichiosis (HGE) is a potentially fatal, tick-borne disease caused b

60 Human granulocytic ehrlichiosis (HGE) is an emerging febrile systemic disease caused by t

61 Human granulocytic ehrlichiosis (HGE) is an emerging infection caused by an Ehrlichia spe

62 Human granulocytic ehrlichiosis (HGE) is an emerging tick-borne infection with a specific

63 he agent of human granulocytic ehrlichiosis (HGE) is an emerging tick-borne pathogen that resides in

64 Human granulocytic ehrlichiosis (HGE) is an emerging tick-borne zoonosis caused by a stra

65 Human granulocytic ehrlichiosis (HGE) is an emerging tickborne illness caused by an intra

66 Human granulocytic ehrlichiosis (HGE) is an emerging tickborne infection, increasingly re

67 he agent of human granulocytic ehrlichiosis (HGE) is an obligate intracellular bacterium with a tropi

68 Human granulocytic ehrlichiosis (HGE) is caused by infection with an obligatory intracell

69 Human granulocytic ehrlichiosis (HGE) is usually diagnosed by immunofluorescent antibody

70 is (HME) or human granulocytic ehrlichiosis (HGE) may be made on the basis of serologic cross-reactiv

71 Human granulocytic ehrlichiosis (HGE) results in fever, pancytopenia, and mild liver inju

72 studies of human granulocytic ehrlichiosis (HGE) suggest a role for host immune response in resolvin

73 he agent of human granulocytic ehrlichiosis (HGE) to evaluate the importance of these pathways in the

74 he agent of human granulocytic ehrlichiosis (HGE) was assessed in a murine infection model and the ro

75 he agent of human granulocytic ehrlichiosis (HGE) was determined by removing feeding ticks from mice

76 he agent of Human Granulocytic Ehrlichiosis (HGE) was studied to investigate how this pathogen exists

77 h confirmed human granulocytic ehrlichiosis (HGE) were tested for cytoplasmic, nuclear, and platelet

78 he agent of human granulocytic ehrlichiosis (HGE) with primers flanking the hypervariable region, we

79 l system of human granulocytic ehrlichiosis (HGE), C3H/HeJ, C3H-SCID, and Peromyscus leucopus mice we

80 he agent of human granulocytic ehrlichiosis (HGE), Ehrlichia phagocytophila, and Ehrlichia equi proba

81 he agent of human granulocytic ehrlichiosis (HGE), in different groups of adults and children from We

82 he agent of human granulocytic ehrlichiosis (HGE), regardless of host species.

83 tients with human granulocytic ehrlichiosis (HGE), the HGE agent has been seen only in the peripheral

84 he agent of human granulocytic ehrlichiosis (HGE).

85 ng illness, human granulocytic ehrlichiosis (HGE).

86 he agent of human granulocytic ehrlichiosis (HGE).

87 he agent of human granulocytic ehrlichiosis (HGE).

88 ic agent of human granulocytic ehrlichiosis (HGE).

89 e-confirmed human granulocytic ehrlichiosis (HGE).

90 gamma-deficient mice had a markedly elevated HGE bacteria burden with morulae concentration of 282 +/

91 Eleven HGE patient serum samples, a horse anti-HGE serum, and a

92 We previously cloned a gene encoding HGE agent 44-kDa major outer membrane protein and design

93 hich we have termed HER2 gene body enhancer (HGE).

94 reversible upon removal of the extracellular HGE agent bound to the host cells prior to PMA stimulati

95 mans suggest an immunopathological basis for HGE.

96 , a putative cellular receptor component for HGE.

97 gton County, Minnesota, an area enzootic for HGE.

98 A murine model for HGE may be useful to assess pathologic lesions, transmis

99 of the 142 individuals who were positive for HGE had at least one serum sample that also reacted to t

100 c, consistent, and simpler serodiagnosis for HGE than the use of whole infected cells or purified HGE

101 may be more useful in diagnostic testing for HGE.

102 incubated with freshly freed host cell-free HGE agent in vitro.

103 HGE, and sera from horses convalescent from HGE and E. equi infection.

104 GE agent, sera from humans convalescent from HGE, and sera from horses convalescent from HGE and E. e

105 Two clones, one each from HGE agent and E. equi, that were recognized specifically

106 5 was more effective in protecting mice from HGE agent infection than with MAbs 5C11 and 5D13.

107 from dogs and human patients recovering from HGE.

108 ntibodies in 80% of first serum samples from HGE patients.

109 h a low and a high passage of in vitro-grown HGE agent.

110 udy group of individuals suspected of having HGE reaffirmed antibody reactivity to multiple antigens

111 However, HGE agent infection had no effect on IRP-1 binding activ

112 s were higher, however, with the local human HGE isolate, but the difference was not statistically si

113 lyzing the role of the major OMP antigens in HGE agent infection and for serodiagnosis.

114 sions concerning management of tick bites in HGE-endemic areas.

115 eptide was detected by immunofluorescence in HGE stimulated with F. nucleatum cell wall, consistent w

116 ssion of hBD-2 mRNA via multiple pathways in HGE in a pattern that is distinct from that of IL-8 expr

117 fic AnkA antibodies reacted with proteins in HGE agent immunoblots, and AnkA monoclonal antibodies de

118 amily in pathogenesis and immune response in HGE.

119 3) fucosylated molecule, plays a key role in HGE infection, an observation that may help explain the

120 However, these antibodies did not inhibit HGE binding, and anti-CD15s was capable of inhibiting th

121 both E. chaffeensis and E. sennetsu, but not HGE agent, in the acute monocytic leukemia cell line THP

122 both E. chaffeensis and E. sennetsu, but not HGE agent, inclusions in THP-1 cells or the cells of the

123 e definition, as confirmed, probable, or not HGE.

124 ection or are caused by immune activation of HGE deserves further study.

125 We demonstrate that adhesion of HGE to both HL60 cells and normal bone marrow cells dire

126 The agent of HGE (aoHGE) is an obligate intracellular bacterium that

127 N mice can become infected with the agent of HGE (designated aoHGE) by syringe inoculation or tick-bo

128 We conclude that the agent of HGE appears to enter and modify part of the endocytic pa

129 uggest that vacuoles containing the agent of HGE fail to mature into phagolysosomes.

130 Lyme disease and antibodies to the agent of HGE revealed a reproducible pattern of the immune respon

131 sed by Borrelia burgdorferi and the agent of HGE, respectively.

132 ibodies reactive with the etiologic agent of HGE.

133 tween Ehrlichia chaffeensis and the agent of HGE.

134 confirmed and 59 probable (n = 78) cases of HGE as defined by seroconversion or a fourfold or higher

135 The earliest confirmed cases of HGE occurred in 1987 in Wisconsin and 1988 in Florida.

136 Cases of HGE occurred in 21 states; 47 (60%) of the cases occurre

137 112 confirmed cases and 30 probable cases of HGE were identified.

138 mediates play a role in the early control of HGE.

139 d as an improved target for PCR diagnosis of HGE compared with the currently used 16S rRNA gene targe

140 gree and that IFA is useful for diagnosis of HGE in convalescence.

141 equi and HGE agent isolates for diagnosis of HGE will occasionally provide discrepant results and con

142 ance of these pathways in the eradication of HGE bacteria.

143 ts and children without clinical evidence of HGE will test positive for A. phagocytophila antibodies

144 D15s was capable of inhibiting the growth of HGE after its entry into the target cell.

145 approach to the clinical immunodiagnosis of HGE.

146 The incidence of HGE in this region exceeded prior estimates, but it was

147 , but there are few data on the incidence of HGE.

148 genicity- and immunity-related mechanisms of HGE are unknown.

149 differential expression in a murine model of HGE infection and during tick transmission.

150 in splenic neutrophils in a murine model of HGE, demonstrating this phenomenon in vivo.

151 e appropriateness of the mouse as a model of HGE, including its usefulness for the investigation of t

152 Laboratory mice are valuable models of HGE agent infection kinetics and immunity, but initial s

153 within 24 h of attachment, and the number of HGE agent organisms increased in larval ticks during fee

154 Onset of HGE was identified from April through December, with cas

155 ole for host immunity in the pathogenesis of HGE.

156 l to examine immunity in the pathogenesis of HGE.

157 laboratory feature during the acute phase of HGE infection.

158 dy staining or polymerase chain reaction) of HGE; 89 were confirmed cases, and 48 were probable cases

159 s observed in the 16S rRNA gene sequences of HGE agent and E. equi isolates from northern California.

160 inetics and immunity, but initial studies of HGE infection in mouse models have failed to demonstrate

161 atory diagnosis and epidemiological study of HGE.

162 with an acute febrile illness suggestive of HGE were identified.

163 and killing capacity underlie the tropism of HGE for granulocytic HL-60 cells and, conversely, the re

164 with Ehrlichia equi-infected neutrophils or HGE agent-infected cultured HL60 cells.

165 ectin glycoprotein ligand, PSGL-1, prevented HGE cell binding and infection, as did enzymatic digesti

166 n annual incidence of confirmed and probable HGE was 9.3 cases per 100,000 residents; there was no in

167 g the 78 patients with confirmed or probable HGE.

168 We used recombinant protein HGE-44, expressed and purified as a maltose-binding prot

169 from the host cells, noninfectious purified HGE agent stored frozen and thawed also had antiapoptoti

170 the use of whole infected cells or purified HGE agents.

171 Recombinant HGE-44, expressed and purified as a glutathione transfer

172 om two aoHGE-infected mice bound recombinant HGE-44.

173 We conclude that recombinant HGE-44 antigen is a suitable antigen in an ELISA for the

174 tein antigen genes, we prepared and screened HGE agent and Ehrlichia equi genomic DNA expression libr

175 Some HGE agent and E. chaffeensis inclusions colocalized with

176 Suspected HGE cases were classified, according to the national cas

177 Active surveillance for suspected HGE was conducted from 1997 through 1999 in a 13-county

178 racterized HGE and 9 patients with suspected HGE who were investigated by PCR, blood smear examinatio

179 lood samples from 31 patients with suspected HGE who were previously tested by 16S rRNA gene (16S) PC

180 These results demonstrate that HGE bacteria induce IL-8 production by host cells and, p

181 RT-PCR demonstrated that HGE organisms inhibited mRNA expression of a single comp

182 We now show that HGE bacteria, and the HGE-44 protein, induce IL-8 secret

183 The HGE agent and E. equi are antigenically diverse, and int

184 The HGE agent did not prevent O(2-) generation in human peri

185 The HGE agent induced a significant delay in morphological a

186 The HGE agent induced expression of interleukin-1beta (IL-1b

187 The HGE starts from the 3' end of intron 19 and extends into

188 otting using purified E. chaffeensis and the HGE agent as antigens suggested that heat shock and othe

189 These results suggest that E. equi and the HGE agent found in California are similar or identical b

190 nfection of mice with B. burgdorferi and the HGE agent modulates host immune responses, resulting in

191 f dual infection with B. burgdorferi and the HGE agent on the course of murine Lyme arthritis and gra

192 dorferi reacted positively with rP44 and the HGE agent.

193 We now show that HGE bacteria, and the HGE-44 protein, induce IL-8 secretion in a promyelocytic

194 h an obligatory intracellular bacterium, the HGE agent.

195 ecially in geographic regions where both the HGE agent and E. chaffeensis occur.

196 ion of p44-homologous genes expressed by the HGE agent in a tissue culture would assist in understand

197 integrity of or new protein synthesis by the HGE agent was not required for the inhibition; carbohydr

198 e three cytokines in PBLs by rP44 and by the HGE agent were similar.

199 ected or have been infected naturally by the HGE agent with low-level persistent infection or frequen

200 ecific prevention of O(2-) generation by the HGE agent would be critical in survival of the HGE agent

201 rging febrile systemic disease caused by the HGE agent, an obligatory intracellular bacterium of gran

202 ng NADPH oxidase in human neutrophils by the HGE agent.

203 ent P44-homologous proteins expressed by the HGE agent; and (vi) demonstrated existence of antibodies

204 train of Anaplasma phagocytophila called the HGE agent, an obligatory intracellular bacterium.

205 We previously isolated and cultivated the HGE agent in the promyelocytic leukemia cell line HL-60

206 All assays detected the HGE agent in blood during early infection, but PCR and t

207 ene fragment is identical among E. equi, the HGE agent, and E. phagocytophila, with the exception of

208 a single mouse was culture positive for the HGE agent.

209 Furthermore, the HGE agent completely prevented O(2-) release by neutroph

210 h human granulocytic ehrlichiosis (HGE), the HGE agent has been seen only in the peripheral blood gra

211 To determine if the HGE agent delays the apoptosis of human peripheral blood

212 ed from the p44-18 gene were detected in the HGE agent cultivated in HL-60 cells at 37 degrees C, but

213 transcribed from p44-homologous genes in the HGE agent cultivated in HL-60 cells; (ii) cloned genes c

214 es being expressed were not clustered in the HGE agent genome; (iv) estimated that a minimum copy num

215 ggests that histopathological lesions in the HGE murine model do not result from direct ehrlichia-med

216 cer function and that DNA methylation in the HGE region inhibits the histone modifications characteri

217 In tick cell layers, the HGE agent induced foci of infection that caused necrotic

218 The 444 Ep-ank gene of the HGE agent and E. equi isolates from northern California

219 onal antibodies to the 44-kDa antigen of the HGE agent and was infectious for laboratory mice.

220 gest that the 43- and 45-kDa proteins of the HGE agent are encoded by members of the GE MSP-2 multige

221 cells, proving that the blood stages of the HGE agent are infectious for tick cells, as are those re

222 p44 multigene family in transmission of the HGE agent between mammals and ticks.

223 cell culture isolation of two strains of the HGE agent directly from an infected horse and a dog and

224 hese studies suggest that replication of the HGE agent during and after feeding in larvae and during

225 experimental process for transmission of the HGE agent from infected mice (a reservoir model) to nymp

226 tment within HL-60 cells: early forms of the HGE agent have a round reticular appearance while later

227 NOS2(-/-) mice had delayed clearance of the HGE agent in comparison to control or gp91(phox-/-) mice

228 urface properties between populations of the HGE agent in different host environments.

229 n by the major outer membrane protein of the HGE agent in monocytes, which are not the primary host c

230 Proteinase K treatment of the HGE agent or rP44 eliminated the ability to induce these

231 g was used to characterize the nature of the HGE agent replicative inclusions and to compare them wit

232 hat binding of a protein component(s) of the HGE agent to neutrophils and subsequent cross-linking an

233 carbohydrate but not surface protein of the HGE agent was required.

234 Sequence-confirmed products of the HGE agent were amplified from three individuals residing

235 t 44-kDa major surface protein (rP44) of the HGE agent were examined by reverse transcription-PCR and

236 which are not the primary host cells of the HGE agent, contributes to HGE pathogenesis and immunomod

237 volved in the antiapoptotic mechanism of the HGE agent.

238 ine, blocked the antiapoptotic effect of the HGE agent.

239 E agent would be critical in survival of the HGE agent.

240 as determined to be identical to that of the HGE agent.

241 jor antigenic outer membrane proteins of the HGE agent.

242 two PCR-positive mice, contained DNA of the HGE agent.

243 ion of antibodies to a 44-kDa protein of the HGE agent.

244 ere primarily present on the membrane of the HGE agent.

245 is identical to the 16S rDNA sequence of the HGE agent.

246 ultivated in HL60 cells for isolation of the HGE agent.

247 and overrode the antiapoptotic effect of the HGE agent.

248 t or reverse the antiapoptotic effect of the HGE agent.

249 ing to the mRNAs from the genomic DNA of the HGE agent; (iii) showed that the genes being expressed w

250 Although only the HGE agent was present in northwestern Pennsylvania, both

251 blot analysis, all three MAbs recognized the HGE agent but not Ehrlichia chaffeensis, Ehrlichia senne

252 Although much weaker than the HGE agent freshly freed from the host cells, noninfectio

253 These data demonstrate that the HGE agent elicits a prominent IFN-gamma response in mice

254 These results suggest that the HGE agent resides in inclusions which are neither early

255 Electron microscopy demonstrated that the HGE organism resides in a membrane-bound compartment wit

256 Thus, the HGE bacterium specifically bound to fucosylated leukocyt

257 Reactivity to the HGE agent and to either Coxiella burnetii, Rickettsia ri

258 to E. chaffeensis also had antibodies to the HGE agent in at least one serum sample.

259 version or a fourfold or higher titer to the HGE agent than to the Ehrlichia chaffeensis antigens.

260 ctor beta, and IL-2 mRNAs in response to the HGE agent was not remarkable.

261 Antibodies reactive to the HGE agent were detected in 142 (8.9%) of 1,602 individua

262 ot TNF-alpha or IL-6 mRNA in response to the HGE agent, whereas monocytes expressed all three of thes

263 positive blood samples were identical to the HGE agent.

264 ity to detect WB-confirmed antibodies to the HGE agent.

265 ng feeding in nymphs is a means by which the HGE agent overcomes inefficiencies in acquisition of inf

266 olorado had antibodies that reacted with the HGE agent (genus GMT = 194), suggesting that enzootic cy

267 ent strains of mice were inoculated with the HGE agent and assayed for production of polyclonal and m

268 Sera from two patients coinfected with the HGE agent and B. burgdorferi reacted positively with rP4

269 Infection of mice with the HGE agent does not induce diagnostically significant B.

270 l blood leukocytes (PBLs) incubated with the HGE agent or a recombinant 44-kDa major surface protein

271 ee sera that were IFA positive only with the HGE agent were examined by Western immunoblot analysis u

272 ies from rabbits and mice immunized with the HGE agent, sera from humans convalescent from HGE, and s

273 rP44, regardless of IFA reactivity with the HGE agent.

274 ocytopenic in response to infection with the HGE agent.

275 and C57BL/6J mice during infection with the HGE agent.

276 Therefore, HGE bacteria repress the respiratory burst by down-regul

277 The three HGE-agent-only IFA-positive sera reacted only with rP44,

278 Thus, HGE is an important cause of morbidity and is now the se

279 TFAP2C, a known regulator of HER2, binds to HGE and is required for its enhancer function and that D

280 host cells of the HGE agent, contributes to HGE pathogenesis and immunomodulation.

281 > vitamin D3) correlated with resistance to HGE.

282 2), derived from HL60 cells and resistant to HGE, was deficient in the expression of alpha-(1, 3)fuco

283 is highly correlated with susceptibility to HGE, and it, and/or a closely related sialylated and alp

284 g differentiation-specific susceptibility to HGE.

285 Cells susceptible to HGE express sialylated Lewis x (CD15s), a ligand for cel

286 d the sensitivity and specificity of various HGE agent and E. equi antigens used for IFA diagnosis by

287 The inhibition was HGE agent dose dependent, required ehrlichial contact wi

288 e USG3 strain and another with the Wisconsin HGE and Minnesota canine sequences.

289 ihydroxyvitamin D3) and then challenged with HGE.

290 olar-type H+-ATPase was not colocalized with HGE agent inclusions but was weakly colocalized with E.

291 However, HL-60 cells infected with HGE bacteria did not produce O2- upon activation with PM

292 Infection with HGE organisms also decreased gp91phox mRNA levels in spl

293 ly infection of C3H/HeN or C57BL/6 mice with HGE bacteria.

294 odies in eight sera from eight patients with HGE and in two sera from two aoHGE-infected mice bound r

295 The average age of patients with HGE was 57 years, and males accounted for 53 (68%) of th

296 the two proteins in sera from patients with HGE.

297 ocytic ehrlichiosis (HME) did not react with HGE-44-MBP antigen, except for one sample (specificity,

298 Rodents with HGE agent-specific antibodies were found in New York (23

299 lowest homology occurring between a New York HGE agent and the Swedish E. phagocytophila.

300 ate clades, one including the three New York HGE samples and the USG3 strain and another with the Wis