back to the future - chronic lyme studies

From: zipzip (mcpucho_at_hotmail.com)
Date: 01/04/05 

Date: 3 Jan 2005 23:15:04 -0800

the following is from the 1996 LDF conference.

how did we go from this to sharing the stage at the OHME conference in
2005? we lost 10 freaking years. i'd rather have klempner than
klinghart presenting.

what the f*** happened?

there has been a conversation about lyme leaders. from the archives it
looks like the LDF was doing a much better job than the LDA or ILADS.
what happened to the journal of spirochetal and tick borne diseases?

after lymerix, then what?

all down hill....

meanwhile their is more and more evidence that chronic lyme is indeed
an "autoimmune" disease.

Mario T. Philipp, PhD
Senior Research Scientist, Department Chairman
Tulane Regional Primate Research Center

"Chronic Lyme Disease in the Rhesus Monkey"
Philipp MT (1), Bohm Jr RP (1), Dennis VA (1), England J (2), Lowrie
Jr RC (1), Roberets ED (1). (1) Department of Parasitology, Tulane
University Primate Research Center. (2) Department of Neurology,
Louisiana State University

"We investigated the appearance of arthritis and neuroborreliosis, as
well as humoral and cellular immune responses in rhesus macaques
inoculated with Borrelia burgdorferi sensu stricto (strain JD 1)
during 3,6, and 46 months post-inoculation (PI). sixteen animals were
inoculated by the bite of Ixodes scapularis nymphs, 3 by needle
inoculation and 6 were controls. Signs of arthritis were investigated
clinically by physical examination, and post-mortem both at the gross
and microscopic levels. Signs of neuroborreliosis were sought for in
the same way and, in addition, by nerve conduction studies and nerve
biopsies. Longitudinal analysis (greater than 52 weeks PI) of serum
antibody indicated a gradual increase in the number of antigens
recognized by IgG antibodies on Western blots and a high anti-p39 IgG
antibody ELISA titer that reached a plateau of 1:8700 (geometric mean
titer) by 10 wks PI. Blastogenesis of peripheral blood mononuclear
cells qualified in response to whole killed spirochetes revealed that
animals undergo periods of responsiveness interspersed with prolonged
intervals of unresponsiveness (10-30 weeks), in face of a persistent
antibody response. At the gross level, no joint abnormalities were
observed 3 months PI, whereas all of the infected animals showed gross
joint abnormalities 6 months PI. Microscopic lesions were apparent at
both time points in all animals, most frequently in the knee and elbow
joints. Forty six months PI , 1 of 6 animals examined post-mortem
showed marked cartilage destruction with synovial cell hyperplasia and
periarticular fibrosis in several joints. Peripheral neuritis
involving multiple nerves was the most prominent and consistent
neurologic manifestation at 3 months PI. In contrast, by 6 months PI,
inflammation was rarely seen, whereas axonal degeneration was
prominent. Neuropathologic changes were observed also in the CNS, but
to a lesser extent. Sural nerve biopsies indicated a reduction in the
number of myelinated nerve fibers in animals which showed, by nerve
conduction studies, a pattern and type of peripheral neuropathy best
characterized as primarily an axonal-degeneration subtype of
mononeuropathy multiplex. Nerve conduction eventually returned to
normal in all animals and, concomitantly, regenerative changes such as
neuroma or fibrosis were observed in biopsies of some animals.
Possible etiologies of the neuropathy observed include localized
direct infection within nerve, focal immune-mediated attack on nerve,
or focal ischemia of nerve."

PATHOGENESIS OF CHRONIC LYME DISEASE

Janis Weis, PhD
Associate Professor, Department of Pathology, University of Utah
School of Medicine

"Correlation of Severity of Arthritis with Level of Persistence of
Spirochetes in Murine Lyme Disease"

In human Lyme disease symptoms with wide ranging levels of severity
have been observed. A mouse model of Lyme disease has been developed
by Barthold and colleagues that allows analysis of mice with mild,
moderate and severe pathologies after inoculation with the spirochete
Borrelia burgdorferi. To determine whether the difference in symptoms
reflects differences in the number of spirochetes persisting in
affected tissues, a sensitive PCR technique was developed to detect B.
burgdorferi DNA in virtually any tissue of an infected mouse. This
analysis, which detects DNA from as few as 3 spirochetes revealed the
presence of B. burgdorferi DNA in many tissues from severely arthritis
C3H/HeJ mice as early as 1 week post infection. The heart, ear, and
ankle were particularly heavily infected although B. burgdorferi DNA
was also detected in spleen, liver, brain, kidney, bladder, uterus,
and lymph nodes. In contrast, much lower levels of spirochete DNA were
detected in tissues of infected BALB/c mice, which develop less severe
arthritis when infected with B. burgdorferi than do C3H/HeJ mice. This
difference was evident throughout the 5 week analysis. The genetic
resistance to severe arthritis in the BALC/c mouse can be overcome
with a high dose inoculum: both severe arthritis and high levels of
spirochetes in tissues are observed. The genetic regulation of severe
pathology was analyzed by infecting the offspring of a cross between
C3H/HeJ and BALB/c mice. The f1 mice developed severe arthritis and
displayed high levels of Borrelia DNA in the heart and ankle when
infected with the highly virulent N40 strain, similar to the C3H/HeJ
parent. In contrast, infection of the F1 with the less virulent NB19
strain resulted in mild arthritis and persistence of relatively fewer
spirochetes in these tissues, similar to the BALB/c parent. These
findings support the model in which the severity of pathology is
directly related to level of persisting spirochetes in tissues.

Mark Klempner, MD
Professor of Medicine and Vice Chairman for Scientific Affairs
New England Medical Center, Tufts University

"Acquisition and Induction of Enzymes which Degrade the Extracellular
Matrix by Borrelia burgdorferi and other Borrelia Species"

Mark S. Klempner, Linden Hu, Rick Rogers and George Perides. New
England Medical Center. Borrelia burgdorferi is inoculated into the
skin by a tick vector in the Ixodes ricinis/Ixodes persulcatus species
complex. After inoculation into the skin spirochetes spread
centripedally resulting in the characteristic erythema migrans lesion.
Subsequently, the organisms disseminate resulting in a clinical
syndrome which principally involves the central nervous system, heart,
diarthrodial joints and the skin. For virtually all bacteria which
disseminate from a skin or soft tissue inoculation site bacterial
proteases, which digest extracellular matrix proteins, facilitate
spreading in the skin and subsequent invasion into the lymphatic or
vascular circulations. We have found that B. burgdorferi lacks these
proteases but is able to spread from its inoculation site in the skin.
Instead, B. burgdorferi has evolved a mechanism for accomplishing this
step in pathogenesis by utilizing human proteases which are generated
at the inoculation site and become bound to the bacterial surface.
More specifically, at the vascular injury site created by the tick
vector, B. burgdorferi binds human urokinase type plasminogen
activator (uPA) and human plasminogen (Pgn) which generates bioactive
human plasmin on the surface of the spirochete. Human plasmin bound to
B. burgdorferi is a highly stable, non-immunogenic, potent serine
protease with broad substrate specificity including extracellular
matrix and basement membrane components. Other borrelia species also
bind uPA and Pgn and generate plasmin on the surface of the
spirochete. We have also discovered that B. burgdorferi induces the
release of enzymes that degrade the extracellular matrix from cells in
the skin and the central nervous system. Utilization of host proteases
instead of proteases of microbial origin could explain why the immune
response to B. burgdorferi proteases of microbial origin could explain
why the immune response to B. burgdorferi infection is blunted. These
observations represent a new mechanism for bacterial virulence which
may identify new targets for prevention, diagnosis, and treatment of
Lyme disease.

Relevant Pages

  • Lyme & the Bladder-
    ... Then my bladder was normal after IV ... Lyme disease, which is caused by the spirochete Borrelia burgdorferi, ... patient bladder infection by the Lyme spirochete was documented on ... experimentally infected with Lyme spirochetes, ...
    (sci.med.diseases.lyme)
  • Lyme & the Bladder-
    ... Urinary dysfunction in Lyme disease. ... Lyme disease, which is caused by the spirochete Borrelia burgdorferi, ... patient bladder infection by the Lyme spirochete was documented on ... experimentally infected with Lyme spirochetes, ...
    (sci.med.diseases.lyme)
  • Re: back to the future - chronic lyme studies
    ... > there has been a conversation about lyme leaders. ... > the same way and, in addition, by nerve conduction studies and nerve ... > Spirochetes in Murine Lyme Disease" ... > burgdorferi DNA in virtually any tissue of an infected mouse. ...
    (sci.med.diseases.lyme)
  • Re: Interstitial Cystitis!!
    ... My theory would be that Lyme attacks the nerve endings in the bladder. ... Lyme disease, which is caused by the spirochete Borrelia burgdorferi, ... spirochetes, including BALB/c mice, nude mice (M. ...
    (sci.med.diseases.lyme)
  • Re: Antibotics
    ... Not when you only have a CNS infection. ... It would depend on the vaccine. ... a Bacteriophage of Borrelia burgdorferi -- ... Lyme disease, proved to be a newly recognized disorder characterized by ...
    (sci.med.diseases.lyme)
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