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Volume: 6
Issue: 01
Date: 15-Jan-98


Table of Contents:

I.    LYMENET: U-Penn Using PCR To Unlock Lyme Mysteries
II.   ARCH NEUROL: Post-Lyme syndrome and chronic fatigue syndrome.
      Neuropsychiatric similarities and differences.
III.  PROC NATL ACAD SCI: Therapeutic passive vaccination against
      chronic Lyme disease in mice.
IV.   ZENTRALBL BAKTERIOL: The isolation of Borrelia burgdorferi
      spirochetes from clinical material in cell line cultures.
V.    ABOUT THE LYMENET NEWSLETTER


Newsletter:

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                   Volume 6 / Number 01 / 15-JAN-98
                                INDEX


I.    LYMENET: U-Penn Using PCR To Unlock Lyme Mysteries
II.   ARCH NEUROL: Post-Lyme syndrome and chronic fatigue syndrome.
     Neuropsychiatric similarities and differences.
III.  PROC NATL ACAD SCI: Therapeutic passive vaccination against
     chronic Lyme disease in mice.
IV.   ZENTRALBL BAKTERIOL: The isolation of Borrelia burgdorferi
     spirochetes from clinical material in cell line cultures.
V.    ABOUT THE LYMENET NEWSLETTER



=====*=====


I.    LYMENET: U-Penn Using PCR To Unlock Lyme Mysteries
--------------------------------------------------------
BYLINE: By Marc C. Gabriel
DATE: January 9, 1998


Researchers at the University of Pennsylvania are looking to discover
why some Lyme patients continue to exhibit objective signs of infection
despite supposedly adequate antibiotic therapy.  To this end, they are
seeking samples from patients for analysis.


Dr. H. Ralph Schumacher, Director of the Rheumatology-Immunology Center
at the University of Pennsylvania School of Medicine, is leading the
Lyme project.  Dr. Schumacher is continuing the work previously
performed by Drs. Manfred and Margaret Bayer at the Fox Chase Cancer
Center in Philadelphia.  Funding is being provided by the Lyme Disease
Association of New Jersey.


At the most basic level, the project will use the polymerase chain
reaction (PCR) method to attempt detection of Borrelia burgdorferi
(Bb), the causitive agent of Lyme disease, in urine and synovial fluid
samples.  These results will be analyzed along with the patient's
clinical, diagnostic and treatment data.


Subsequently, if funding permits, the researchers plan to investigate
some basic aspects of how Borrelia invade and possibly persist in
tissues.  They will develop in situ hybridization to localize DNA or
RNA of Bb.  The cytokines produced by the cells surrounding Bb will
be examined to see if certain people produce more cytokines that make
it more difficult to eliminate infections.  Measures other than
antibiotics may be needed for such patients.


"Physician participation in this project is essential," says
Patricia V. Smith, President of the Lyme Disease Association of New
Jersey.  "Patients and physicians alike have faced a myriad of problems
associated with the diagnosis and treatment of Lyme disease -
especially chronic Lyme disease.  The studies conducted by Dr. Bayer
and Dr. Schumacher, utilizing the latest molecular biology techniques,
will help us to further elucidate the complexities of diagnosis,
pathogenesis, and persistence of the organism."


All samples sent to Dr. Schumacher must be submitted by a physician.
The Lyme Disease Network will make the required paper forms available
for download and printing at their home page at:


                  http://www.lymenet.org/upenn/

The PCR technique for Bb detection has been in use for many years.
Numerous commercial laboratories, including IgeneX Labs and BBI
North American Labs, have been performing this test for several years.



=====*=====


II.   ARCH NEUROL: Post-Lyme syndrome and chronic fatigue syndrome.
     Neuropsychiatric similarities and differences.
-------------------------------------------------------------------
AUTHORS: Gaudino EA, Coyle PK, Krupp LB
ORGANIZATION: Department of Neurology, State University of New York at
             Stony Brook, USA.
REFERENCE:  Arch Neurol 1997 Nov;54(11):1372-6
ABSTRACT:


BACKGROUND: Patients with chronic fatigue syndrome (CFS) and post-Lyme
syndrome (PLS) share many features, including symptoms of severe
fatigue and cognitive difficulty.
OBJECTIVE: To examine the neuropsychiatric differences in these
disorders to enhance understanding of how mood, fatigue, and cognitive
performance interrelate in chronic illness.
METHODS: Twenty-five patients with CFS, 38 patients with PLS, and 56
healthy controls participated in the study.  Patients with CFS met 1994
criteria for CFS and lacked histories suggestive of Lyme disease.
Patients with PLS were seropositive for Lyme disease, had met the
Centers for Disease Control and Prevention criteria, or had histories
strongly suggestive of Lyme disease and were experiencing severe
fatigue that continued 6 months or more following completion of
antibiotic treatment for Lyme disease.  All subjects completed
self-report measures of somatic symptoms and mood disturbance and
underwent neuropsychological testing.  All patients also underwent
a structured psychiatric interview.

RESULTS: Patients with CFS and PLS were similar in several somatic
symptoms and in psychiatric profile.  Patients with CFS reported
more flulike symptoms than patients with PLS. Patients with PLS but
not patients with CFS performed significantly worse than controls on
tests of attention, verbal memory, verbal fluency, and motor speed.
Patients with PLS without a premorbid history of psychiatric illness
did relatively worse on cognitive tests than patients with PLS with
premorbid psychiatric illness compared with healthy controls.
CONCLUSIONS: Despite symptom overlap, patients with PLS show greater
cognitive deficits than patients with CFS compared with healthy
controls.  This is particularly apparent among patients with PLS who
lack premorbid psychiatric illness.



=====*=====


III.  PROC NATL ACAD SCI: Therapeutic passive vaccination against
     chronic Lyme disease in mice.
-----------------------------------------------------------------
AUTHORS: Zhong W, Stehle T, Museteanu C, Siebers A, Gern L, Kramer M
        Wallich R, Simon MM
ORGANIZATION: Max-Planck-Institut fur Immunbiologie, Stubeweg 51,
             D-79108 Freiburg, Germany.
REFERENCE: Proc Natl Acad Sci U S A 1997 Nov 11;94(23):12533-8
ABSTRACT:


Passive and active immunization against outer surface protein A (OspA)
has been successful in protecting laboratory animals against
subsequent infection with Borrelia burgdorferi.  Antibodies (Abs) to
OspA convey full protection, but only when they are present at the
time of infection.  Abs inactivate spirochetes within the tick and
block their transmission to mammals, but do not affect established
infection because of the loss of OspA in the vertebrate host.  Our
initial finding that the presence of high serum titers of anti-OspC
Abs (5 to 10 &mgr;g/ml) correlates with spontaneous resolution of
disease and infection in experimentally challenged immunocompetent
mice suggested that therapeutic vaccination with OspC may be feasible.
We now show that polyclonal and monospecific mouse immune sera to
recombinant OspC, but not to OspA, of B. burgdorferi resolve chronic
arthritis and carditis and clear disseminated spirochetes in
experimentally infected C.B.-17 severe combined immunodeficient mice
in a dose-dependent manner.  This was verified by macroscopical and

microscopical examination of affected tissues and recultivation of
spirochetes from ear biopsies.  Complete resolution of disease and
infection was achieved, independent of whether OspC-specific immune
sera (10 microg OspC-specific Abs) were repeatedly given (4x in 3- to
4-day intervals) before the onset (day 10 postinfection) or at the
time of fully established arthritis and carditis (days 19 or 60
postinfection).  The results indicate that in mice spirochetes
constitutively express OspC and are readily susceptible to protective
OspC-specific Abs throughout the infection.  Thus, an OspC-based
vaccine appears to be a candidate for therapy of Lyme disease.



=====*=====


IV.   ZENTRALBL BAKTERIOL: The isolation of Borrelia burgdorferi
     spirochetes from clinical material in cell line cultures.
----------------------------------------------------------------
AUTHORS: Tylewska-Wierzbanowska S, Chmielewski T
ORGANIZATION: Department of Bacteriology, National Institute of
             Hygiene, Warsaw, Poland.
REFERENCE: Zentralbl Bakteriol 1997 Oct;286(3):363-70
ABSTRACT:


It has been found that B. burgdorferi bacteria multiply in mouse
fibroblasts.  Mouse fibroblast of the L-929 cell line was inoculated
with less than 10 up to 10(4) B. burgdorferi cells and incubated for
2-10 days at 35 degrees C in microaerophilic conditions.  Within 2
days, visible growth was observed.  The bacteria were present in
growth medium and on/in mouse fibroblasts as revealed by the indirect
immunofluorescence assay.  At the same time, development of vacuolized
fibroblastic giant cells was observed.  Viable spirochetes were also
detected in Eagle's medium from a L-929 fibroblast cell line culture,
after approximately 2-5 days of incubation with blood, cerebro-spinal
and synovial fluids of Lyme borreliosis patients.  The bacteria were
present in growth medium and on/in endothelial cells as revealed by
the indirect immunofluorescence assay.  The establishment of B.
burgdorferi culture conditions in cell lines gives us a possibility
to isolate the etiological agent of Lyme disease from patient blood,
cerebrospinal and synovial fluids at different stages of infection.

The high sensitivity of this procedure would be helpful in a proper
identification of the infection as well as in the control of treatment
effectiveness.



=====*=====


V.    ABOUT THE LYMENET NEWSLETTER
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