Evidence map›Paper›PMID 15111322›Full record

ArticleThe American journal of pathology2004

Urease expression by Cryptococcus neoformans promotes microvascular sequestration, thereby enhancing central nervous system invasion.

Michal A Olszewski, Mairi C Noverr, Gwo-Hsiao Chen, Galen B Toews, Gary M Cox, John R Perfect, Gary B Huffnagle

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.

0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

156 citing papers in PubMed, 285 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. The Pain Is in the Brain With the Sugar-Coated Killer.The Journal of infectious diseases · 2025
    Review
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  7. Article
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  9. Article
  10. Article
  11. Review
  12. Article
  13. DoesFuture microbiology · 2025
    Article
  14. Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  15. Review
  16. The emergence of neuroinvasiveFrontiers in cellular and infection microbiology · 2025
    Article
  17. Review
  18. Article
  19. Article
  20. Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024
    Review

96 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Michal A OlszewskiVeteran's Administration Medical Center Ann Arbor, Ann Arbor, Michigan, USA. olszewsm@umich.edu
Mairi C Noverr
Gwo-Hsiao Chen
Galen B Toews
Gary M Cox
John R Perfect
Gary B Huffnagle
University of Michigan–Ann Arbor · USAnn Arbor VA Medical Center · USDuke Medical Center · US

Funding

PULMONARY CELLULAR AND MOLECULAR BIOLOGY TRAININGT32HL007749 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Pickett Dickson · 1993 to 2026
$19.9M
MACROPHAGE RECRUITMENT/ACTIVATION IN LUNG DEFENSER01HL051082 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TOEWS, GALEN B · 1994 to 2007
$2.5M
GENTIC &MOLECULAR BIOLOGY OF VIRULENCE IN C. NEOFORMANSR01AI028388 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 1991 to 2004
$1.9M
MODULATION OF TH1/TH2 RESPONSES BY INNATE IMMUNITYR01HL065912 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUFFNAGLE, GARY B. · 2000 to 2004
$1.5M
CHEMOKINE RECEPTORS IN IMMUNITY TO C NEOFORMANSR01HL063670 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUFFNAGLE, GARY B. · 1999 to 2003
$1.1M
NHLBI NIH HHS R01 HL051082NHLBI NIH HHS R01 HL065912NHLBI NIH HHS R01-HL51082NHLBI NIH HHS R01-HL63670NHLBI NIH HHS R01-HL65912NHLBI NIH HHS T32 HL007749NHLBI NIH HHS T32-HL07749NIAID NIH HHS R01 AI028388NIAID NIH HHS R01-AI28388Wellcome Trust
6 · The paper itself

Abstract

Our objective was to determine the role of the cryptococcal virulence factor urease in pulmonary-to-central nervous system, dissemination, invasion, and growth. C. neoformans H99, the urease knockout strain (ure1) derived from H99, and the urease restored strain ure1+URE1-1 were used for the studies. The absence of cryptococcal urease (ure1infection) resulted in significant protection from the high mortality observed in H99-infected mice. All H99-infected mice had extremely high cryptococcal loads in their brains at the time of death, whereas only two of six animals that died of ure1 infection had detectable C. neoformans in the brain. Histological analysis of the blood-to-brain invasion by C. neoformans H99 demonstrated wedging of the yeasts in small capillaries, altered structure of microvessel walls, formation of mucoid cysts initiated in the proximity of damaged microcapillaries, and the absence of an inflammatory response. Direct inoculation of H99, ure1, and ure1+URE1-1 into the brain demonstrated that urease was not required to grow in the brain. However, the dissemination patterns in the brain, spleen, and other organs after intravenous inoculation indicated that cryptococcal urease contributes to the central nervous system invasion by enhancing yeast sequestration within microcapillary beds (such as within the brain) during hematogenous spread, thereby facilitating blood-to-brain invasion by C. neoformans.

Indexed as

MicrocirculationAnimalsBrainCapillariesCentral Nervous SystemColony-Forming Units AssayCryptococcus neoformansGene DeletionLungMacrophages, PeritonealMiceMice, Inbred C57BLMice, KnockoutTime FactorsUreaseUrease

Identifiers

PMID15111322
PMCPMC1615675
OpenAlexW2085415570

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.