| Fondoo 2005-10-24, 12:55 am |
| From what I gather here http://www.duesberg.com/articles/ept4cells.html
is he supports the theory that cell death is the result of the oxidizing
agents the cultures are exposed to and not to the HIV that is also
present
Again thank you for the input Chris
Cut-n-Paste
The conclusion that HIV has an "intrinsic effect" on PCD can be questioned
on several grounds:
1. The "slight acceleration of the first signs of apoptosis" in the
stimulated HIV infected cultures, as compared to the non-HIV infected
stimulated cultures, may not be due to HIV but to the many non-HIV factors
present in "HIV" inocula, including:
(a) Mycoplasmas and other infectious agents;
(b) The many cellular proteins present in the "HIV preparation" (Henderson
et al., 1987);
(c ) PHA, present in the cultures from which the "HIV preparation" was
derived;
2. That HIV is not the cause of apoptosis is also indicated by the fact
that in chronically infected cell lines in which virus is continuously
produced, apoptosis is not detected;
3. That HIV may play no role in apoptosis is also suggested by the
presently accepted mechanism of apoptosis. Apoptosis occurs both in
healthy and in pathological conditions, is frequently prominent amongst
the proliferating cells of lymphoid germinal centres, and can be enhanced
by numerous agents including radiation, cytotoxic drugs, corticosteroids
and the calcium ionophore A23187 (Kerr & Searle, 1972; Don et al., 1977;
Wyllie et al., 1980; Wyllie et al., 1984). Apoptosis is cellular death
characterised by morphological criteria: cellular condensation, DNA
fragmentation, and plasma membrane "blebbing" leading to the release of
"apoptic bodies" which vary widely in size and some of which contain
pyknotic chromatin surrounded by intact membranes (Kerr & Searle, 1972;
Don et al., 1977; Wyllie et al., 1980; Wyllie et al., 1984). These changes
are thought to be induced by increased concentration of Ca++ which in its
turn induces contraction of the cytoskeleton whose main components are
known to be the ubiquitous proteins, actin and myosin (Jewell et al.,
1982; Cohen & Duke, 1984; McConkey et al., 1988; McConkey et al., 1989;
Reed, 1990).
However, evidence exists indicating that intracellular Ca++ concentration
and contraction of the actin-myosin system (cellular condensation), are
induced by perturbances in the cellular redox state (Papadopulos-Eleopulos
et al., 1985; Papadopulos-Eleopulos et al., 1989b). In fact, for more than
a decade, evidence has existed showing that oxidising agents, including
all mitogenic (activating) agents, can induce: reversible cellular
changes; cellular activation; malignant transformation; mitogen
unresponsive cells; or cellular death, including death by apoptosis. The
ultimate outcome depends on the concentration of the agent, its rate of
application, the initial state of the cells and the cellular milieu (See
reference (Papadopulos-Eleopulos, 1982)).
More recent data confirm the fact that the intracellular free Ca++
concentration is regulated by the cellular redox state. Oxidation leads to
an increased, and reduction to a decreased, Ca++ concentration (Trimm et
al., 1986). Cellular surface blebbing (Jewell et al., 1982; Lemasters et
al., 1987; Reed, 1990), chromatin condensation (Pellicciari et al., 1983),
and apoptosis (Morris et al., 1984) are the direct result of cellular
oxidation in general and of cellular sulphydryl groups in particular. This
is supported by Montagnier's group's recent finding that apoptosis can be
inhibited by reducing agents (Ren» et al., 1992). (In fact, at present,
Montagnier (Gougeon & Montagnier, 1993) agrees with our view that
anti-oxidants should be used for treatment of HIV/AIDS patients
(Papadopulos-Eleopulos, 1988; Papadopulos-Eleopulos et al., 1989a; Turner,
1990; Papadopulos-Eleopulos et al., 1992a; Papadopulos-Eleopulos et al.,
1992b)). At present it is also known that:
(a) for the expression of HIV phenomena (RT, virus-like particles,
antigen/antibody reactions), activation (mitogenic stimulation) is a
necessary requirement (Klatzmann & Montagnier, 1986; Ameisen & Capron,
1991; Papadopulos-Eleopulos et al., 1992b);
(b) activation (stimulation) is induced by oxidation
(Papadopulos-Eleopulos, 1982; Papadopulos-Eleopulos et al., 1992b);
Since both AIDS cultures and AIDS patients are exposed to mitogens
(activating agents), all of which are oxidising agents
(Papadopulos-Eleopulos, 1988), both apoptosis and the phenomena upon which
the presence of HIV is based (viral-like particles, RT, antigen/antibody
reactions (WB), "HIV-PCR- hybridisation"), may all be the direct result of
oxidative stress and therefore their specificity questionable
(Papadopulos-Eleopulos, 1988; Papadopulos-Eleopulos et al., 1992a;
Papadopulos-Eleopulos et al., 1992b).
As far back as January 1985 Montagnier wrote, "....replication and
cytopathic effect of LAV can only be observed in activated T4 cells.
Indeed, LAV infection of resting T4 cells does not lead to viral
replication or to expression of viral antigen on the cell surface, while
stimulation by lectins or antigens of the same cells results in the
production of viral particles, antigenic expression and the cytopathic
effect" (Klatzmann & Montagnier, 1986). One year later Gallo and his
colleagues wrote: "the expression of HTLV-III was always preceded by the
initiation of interleukin-2 secretion, both of which occurred only when
T-cells were immunologically [PHA] activated. Thus, the immunological
stimulation that was required for IL-2 secretion also induced viral
expression, which led to cell death" (Zagury et al., 1986). Thus,
relatively early after the appearance of AIDS it was known that HIV is not
sufficient for the appearance of the cytopathic effects. For some unknown
reason, up till 1991 very little (or no) data was presented regarding the
effects of the activating agents themselves on cell survival. However, in
the above discussed 1991 Virology paper, Montagnier and his colleagues
showed that activation, in the absence of HIV, can induce the same
cytopathic effects. In other words, Montagnier and his colleagues have
shown that HIV is neither necessary nor sufficient for the induction of
the cytopathic effects observed in HIV infected cultures. Thus, the
presently available evidence from the in vitro studies does not prove that
HIV has direct cytopathic effects on any T-cells, T4 or T8. The cytopathic
effects observed in the cultures are most likely caused by the many
activating (oxidising) agents to which the cultures are exposed.
Even if HIV were shown to have cytopathic effects, since it is accepted
that "The hallmark of AIDS is a selective depletion of CD4-bearing
helper/inducer" lymphocytes
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