Prelude

This document presents a brief rationale supported by citations and abstracts,
many of which are quite technical and may be of use to an autism-spectrum child's
physicians.

In a small but growing sample of thorough immune panels from autism-spectrum
children (n<15) I often see atypical elevations of EBV, CMV, and/or HHV6. As
mentioned in prior posts, most of these immune-panels reveal other atypicalities
of various sorts. 
     While evaluating one such immune panel wherein the child has atypical EBV
elevations and an elevated number of NK cells, I encountered citations linking
"...hypersensitivity to mosquito bite (HMB) and clonal expansion of EBV-infected
NK cells..." (eg, 1). A query to the autism-list of St. Johns University
produced a number of responses wherein the parent of an autism-spectrum child
described the parent's or the child's atypical responses to mosquito bites. This
document explores *one* possible meaning of those atypical reactions.

The co-occurrence of elevated NK cells and elevated levels of anti-EBV
antibodies is well studied because *some* such individuals proceed to EBV-
related cancers. However, other researchers have noted that "...abnormal
expansions of EBV-infected NK and B cells can be associated with a chronic
benign course." (2). 
     Nonetheless, the associations among severe mosquito bite reactions,
chronic-active EBV infection and unpleasant sequelae are well documented (eg, 3-
4,7-8); thus the presence of a chronic, active EBV infection is potentially
important, and severe mosquito bite reactions may be an early symptom.

What do we mean by "hypersensitivity to mosquito bite"? I'm not sure. I think
that most parents would know whether or not they or a child had mosquito-bite
reactions that were far more noticable than bites received by peers or other
children, and I imagine that any among various underlying causes might account
for those reactions. 
     However, such atypical reactions *may* (in at least some autism-spectrum
kids) be an indication of an underlying, atypical presence of EBV. This
*theoretical* linkage in autism-spectrum kids with atypical reactions to
mosquito bites gains added credence because in the small number of thorough
immune panels I've perused, atypical elevations of EBV are frequent. 
     Kids or adults with chronic, atypical EBV presence may develop skin
symptoms resembling bulla (eg, like a small blister filled with fluid) and
labeled with such fancy medical monikers as "facial vesiculopapular eruptions
mimicking hydroa vacciniforme" or "Hypersensitivity to mosquito bites was noted
in a patient with hydroa vacciniforme-like eruptions" (4-5).

1. If an autism-spectrum child has extreme reactions to mosquito bites, the
conclusion is *not* "Thus he has chronic, atypical EBV." 
     Instead, a more realistic observation is, "I wonder if my child *might*
have chronic, atypical EBV?"; and a practical response might be to request an
initial immune panel for Ig antibodies against herpes class viruses (they are
so synergistic), including a thorough subpanel specific for IgM and IgG
antibodies against various EBV proteins, plus NK-cell count. 

2. Some autism-list parents have reported that vitamins have been helpful, eg,
the B6 information provided by Jean Curtin. Also, we know that B6 is suggested
for autism-spectrum kids, and some such children respond well to B6
supplementation.

Effects of B6 supplementation are diverse. B6 improves immune function,
including responses against viral infections (eg, 9,13); alters tryptophan
metabolism and thereby affects serotonin systems (10); improves many aspects of
immune performance because B6 *decreases* steroid-hormone binding including that
of glucocorticoids and estrogen (11-12); is reduced in people with high protein
intake (14); and promotes neurite outgrowth (15). Thus, just as lithium has
anti-viral effects which may be linked to neurologic improvements in some cases 
of bipolar disorder, so too does B6 supplementation increase antiviral reactions,
a process that may account for minimizing mosquito bite reactions in a child with
an underlying EBV infection.

Treatments effective against EBV are known (eg, 16-20), but as far as I know as
of late May, 1999, using anti-EBV pharmaceuticals against chronic, atypical EBV
infections is not generally done. I wonder why this is so, especially since (i)
the sequelae from chronic, atypical EBV infection can be severe, and (ii) many
of the thorough immune-panels I've perused for parents of autism-spectrum kids
provide documentation of chronic, atypical EBV infections, occasionally co-
occurring with other infections or signs thereof -- eg, CMV, and/or HHV6, and/or
measles, and occasionally graced by other immune atypicalities. 
     I was surprised to find citations documenting that, among its many effects,
B6 inhibits and B6-deficiency elevates glucocorticoid function. This B6 effect
is important and contributes to its anti-viral tendencies -- because steroids
like glucocorticoids and Prednisone are known as immunosuppressants and can
create conditions conducive to the worsening or reactivation of underlying
infections; and I can't help but wonder how many autism-spectrum kids have been
prescribed Prednisone without first having had a thorough immune panel so as to
identify or rule out the likelihood of underlying, atypical infection.
     
So, what do these various notions and citations mean for atypical mosquito bite
reactions? 
     If an autism-spectrum child has extreme reactions to mosquito bites, the
conclusion is *not* "Thus he has chronic, atypical EBV." 
     Instead, a more realistic observation is, "I wonder if my child *might*
have chronic, atypical EBV?"; and a practical response might be to request an
initial immune panel for Ig antibodies against herpes class viruses (they are
so synergistic), including a thorough subpanel specific for IgM and IgG
antibodies against various EBV proteins.

                               Teresa Binstock
                           Independent Researcher
                  Developmental and Behavioral Neuroanatomy

1. Clin Exp Immunol 1999 Mar;115(3):385-92
Characterization of Epstein-Barr virus (EBV)-infected natural killer (NK)
cell proliferation in patients with severe mosquito allergy; establishment
of an IL-2-dependent NK-like cell line.
Tsuge I, Morishima T, Morita M, Kimura H, Kuzushima K, Matsuoka H
Department of Paediatrics, Nagoya University School of Medicine, Japan.

The clinical evidence of a relationship between severe hypersensitivity to
mosquito bite (HMB) and clonal expansion of EBV-infected NK cells has been
accumulated. In order to clarify the mechanism of EBV-induced NK cell
proliferation and its relationship with high incidence of leukaemias or
lymphomas in HMB patients, we studied clonally expanded NK cells from three
HMB patients and succeeded in establishing an EBV-infected NK-like cell
line designated KAI3. Immunoblotting and reverse transcriptase-polymerase
chain reaction (RT-PCR) analyses revealed that KAI3 cells as well as
infected NK cells exhibited an EBV latent infection type II, where EBV gene
expression was limited to EBNA 1 and LMP1. As KAI3 was established by
culture with IL-2, IL-2 responsiveness of peripheral blood NK cells from
patients was examined. The results represented markedly augmented
IL-2-induced IL-2R alpha expression in NK cells. This characteristic
property may contribute to the persistent expansion of infected NK cells.
However, KAI3 cells as well as the NK cells from patients were not
protected from apoptosis induced by either an anti-Fas antibody or
NK-sensitive K562 cells. Preserved sensitivity to apoptosis might explain
the relatively regulated NK cell numbers in the peripheral blood of the
patients. To our knowledge, KAI3 is the first reported NK-like cell line
established from patients of severe chronic active EBV infection (SCAEBV)
before the onset of leukaemias or lymphomas. KAI3 cells will contribute to
the study of EBV persistency in the NK cell environment and its
relationship with high incidence of leukaemias or lymphomas in HMB
patients.
PMID: 10193407, UI: 99209487

2. Kato K et al. Elevated serum soluble Fas ligand in natural killer cell
proliferative disorders.   Br J Haematol 1998 Dec;103(4):1164-6.

3. Mizuki M et al. Natural killer cell-derived large granular lymphocyte
lymphoma of lung developed in a patient with hypersensitivity to mosquito bites
and reactivated Epstein-Barr virus infection. Am J Hematol 1998
Dec;59(4):309-15.
          Department of Hematology and Oncology, Osaka University
          Medical School, Suita, Japan.
          mizuki@bldon.med.osaka-u.ac.jp
ab: A 17-year-old female developed natural killer (NK) cell-derived large
granular lymphocyte (LGL) lymphoma of the lung. She had a past history of
hypersensitivity to mosquito bites (HMB). After an eight-year chronic,
active Epstein-Barr virus (EBV) infection, she developed multiple lung
lesions and pleural effusion. In the effusion, 60% of the cells were LGL.
They were CD2+, 3-, 16+, 56+, 57+, 45RO+/RA + weak, and possessed strong NK
activity. No rearrangement of T-cell-receptor genes was detected. From all
these results, a diagnosis of NK-LGL lymphoma of the lung was made. EB
virus DNA was detected in cells infiltrating the pleural effusion. The
clonality of the LGLs was determined by Southern blot hybridization with
the terminal repeat sequence of EB virus as a probe, and by chromosomal
abnormalities. The patient died from respiratory failure. Necropsy of the
lung revealed diffuse lymphoma composed of polymorphic cells with typical
angiocentric lesions. Reportedly, lymphomas of NK lineage show
predominantly extranodal involvement, and primary lung lesions are rare. In
the pleural effusion of the present case, abnormally high levels of soluble
Fas ligand, interleukin-10 and interferon gamma were detected. This
hypercytokinemia, reflecting the microenvironment of lymphoma cells, may
play a role in the progression of the lymphoma and organ injury in the
lung.
PMID: 9840912, UI: 99054647

4. Am J Hematol 1997 Apr;54(4):276-81
Clonal lymphoproliferation following chronic active Epstein-Barr virus
infection and hypersensitivity to mosquito bites.
Ishihara S, Okada S, Wakiguchi H, Kurashige T, Hirai K, Kawa-Ha K
Department of Pediatrics, Faculty of Medicine, Osaka University, Suita,
Japan.

In order to elucidate the possibility of lymphoproliferation in cases of
chronic active Epstein-Barr virus infection (CAEBV), to clarify the
clonality and genotype of proliferating lymphocytes, and to search for the
factors that induce lymphoproliferation, we studied 11 cases of CAEBV,
using genetical and immunological techniques. Epstein-Barr virus (EBV) DNA
in peripheral mononuclear cells was detected in eight cases by Southern
blotting. Among those eight cases, monoclonal proliferation of EBV
DNA-positive cells was observed in three cases and oligoclonal
proliferation in three cases. In the cases of monoclonal proliferation, one
case manifested T-cell lymphoproliferation and the rest natural killer (NK)
cell lymphoproliferation. The anti-EBV antibody titers in the study did not
have any relativity to lymphoproliferation. On the other hand, three of the
four cases of NK cell lymphoproliferation and one of the two cases of
T-cell lymphoproliferation exhibited hypersensitivity to mosquito bites
(HMB) in their clinical histories, while none of the three
nonlymphoproliferation cases did. These facts indicate that T-cell and NK
cell lymphoproliferative diseases (LPDs) could be more closely associated
with EBV infection than we had previously expected. Also, the anti-EBV
antibody titers may not be the indicator of EBV-associated LPD, and HMB may
be one of the factors that induce EBV-associated LPD.
PMID: 9092681, UI: 97246443

5. Tokura Y et al. Severe mosquito bite hypersensitivity, natural killer cell
leukaemia, latent or chronic active Epstein-Barr virus infection and hydroa
vacciniforme-like eruption. Br J Dermatol 1998 May;138(5):905-6. [letter]

6. Iwatsuki K et al. Clinicopathologic manifestations of Epstein-Barr
virus-associated cutaneous lymphoproliferative disorders. Arch Dermatol 1997
Sep;133(9):1081-6.
               Department of Dermatology, Fukushima Medical
               College, Japan.
OBJECTIVE: To elucidate clinicopathologic manifestations of cutaneous
lymphoproliferative disorders associated with Epstein-Barr virus (EBV)
infection. DESIGN: Retrospective survey of case series. SETTING: University
hospital medical center. PATIENTS: Sixty-five patients with cutaneous
lymphomas and related disorders. MAIN OUTCOME MEASURES: Detection of EBV
genes and EBV-encoded small nuclear RNAs. RESULTS: Evidence of latent EBV
infection was demonstrated in 15 patients: 3 had malignant lymphoma with
clinical features mimicking cytophagic histiocytic panniculitis, 6 had
facial vesiculopapular eruptions mimicking hydroa vacciniforme, 4 had
angiocentric lymphoma, 1 had histiocytoid lymphoma associated with
hemophagocytosis, and 1 had plasmacytoma. Hypersensitivity to mosquito
bites was noted in a patient with hydroa vacciniforme-like eruptions and
another with histiocytoid lymphoma. Angiocentric infiltration of atypical
lymphoid cells was a common histological feature in the patients with
hydroa vacciniforme-like eruptions and angiocentric lymphoma. No evidence
of EBV infection was apparent in 19 patients with mycosis fungoides or
Sezary syndrome, 7 with adult T-cell leukemia or lymphoma, 3 with
lymphomatoid papulosis (type A), and 2 with lymphocytoma cutis. CONCLUSION:
Patients with EBV-associated cutaneous lymphoproliferative disorders
present with unique and diagnostic clinicopathologic features distinct from
those of mycosis fungoides or Sezary syndrome.
Comments:   * Comment in: Arch Dermatol 1997 Sep;133(9):1156-7
PMID: 9301584, UI: 97447133
  ------------------------------------------------------------------------

7. Jpn J Cancer Res 1997 Jan;88(1):82-7
Hypersensitivity to mosquito bites conceals clonal lymphoproliferation of
Epstein-Barr viral DNA-positive natural killer cells.
Ishihara S, Ohshima K, Tokura Y, Yabuta R, Imaishi H, Wakiguchi H,
Kurashige T, Kishimoto H, Katayama I, Okada S, Kawa-Ha K
Section of Pediatrics, Kashiwara Municipal Hospital, Osaka.

In order to clarify the relationship between Epstein-Barr (EB) virus and
hypersensitivity to mosquito bites (HMB), and to search for the mechanism
which induces EB virus-associated lymphoproliferative diseases, we
investigated patients with HMB, using hematological, immunological and
virological techniques. Among 5 cases of HMB, CD56+ cells had proliferated
and CD3+ cells were diminished in 4 cases. Although anti-EB virus antibody
titers were not consistent with chronic active EB virus infection, EB viral
DNA was detected in the peripheral blood mononuclear cells in all 5 cases.
Moreover, EB viral DNA-positive cells had proliferated monoclonally in 4
cases, and biclonally in 1 case. It was proved that most of the EB viral
DNA existed in natural killer (NK) cells through polymerase chain reaction
analysis. These findings suggest that the basis of HMB may be clonal
lymphoproliferation of EB viral DNA-positive NK cells and this
hematological abnormality may induce the characteristic symptoms of HMB. In
some cases, the proliferating NK cells can metamorphose into leukemic
cells, and hemophagocytic syndrome, which has been assumed to be a
complication of HMB, may then occur.
PMID: 9045900, UI: 97197604

7a. Tokura Y et al. Severe hypersensitivity to mosquito bites associated with
natural killer cell lymphocytosis. Arch Dermatol 1990 Mar;126(3):362-8.
     ab: A 2-year-old girl showed exaggerated skin reactions to mosquito bites
and associated general symptoms, including a high temperature, lymphadenopathy,
and hepatosplenomegaly. Peripheral blood lymphocytes contained a high percentage
of CD2+, CD3-, CD4-, CD8-, CD11b+, CD16+, CD38+, CD56+, CD57-, and HLA-DR+ large
granular lymphocytes that exhibited a marked natural killer cell activity.
Immunohistochemically, biopsy specimens taken from the lesional skin
demonstrated an infiltrate of the cells bearing the natural killer cell
phenotype, indicating a role of these cells in the development of the abnormal
skin reactions to mosquito bites and other systemic manifestations. Our case
suggests that natural killer cell lymphocytosis may show severe hypersensitivity
to mosquito bites as the most outstanding manifestation.
PMID: 1689990, UI: 90179238

8. Acta Paediatr 1995 Nov;84(11):1271-5
Chronic active Epstein-Barr virus infection in children in Japan.
Ishihara S, Okada S, Wakiguchi H, Kurashige T, Morishima T, Kawa-Ha K
Department of Paediatrics, Faculty of Medicine, Osaka University, Japan.

The patients with chronic active Epstein-Barr virus infection (CAEBV) in
childhood in Japan are described. Among 39 registered cases, 20 patients
were males and 19 were females. Unlike the X-linked lymphoproliferative
syndrome, there was no hereditary background. The incidence of
hypersensitivity to mosquito bites was high (31.3%) as a past history. Most
patients exhibited hepatomegaly (92.3%), splenomegaly (87.2%) and fever
(84.6%). The incidence of absent anti-EB virus nuclear antigen titres was
unexpectedly low (17.1%). Lymphoreticular disorders and cardiovascular
diseases were major complications. Twenty-four (61.5%) patients died 6
months to 8 years after the onset, mainly of hepatic failure (eight cases),
cardiac failure (five cases), virus-associated haemophagocytic syndrome
(three cases) and haematological malignancies (two cases). This study
reveals the CAEBV in Japan has several clinical features and should be
informative for the pathogenesis of EB virus.
PMID: 8580625, UI: 96162290

9. Dubeski PL et al. Effects of B vitamin injections on plasma B vitamin
concentrations of feed-restricted beef calves infected with bovine
herpesvirus-1. J Anim Sci 1996 Jun;74(6):1358-66.
          Department of Animal Science, Oklahoma State University,
          Stillwater 74078-0425, USA.
ab: For nonruminants, stress and disease greatly increase requirements for
vitamin
B6, folic acid, pantothenic acid, and ascorbate. The effects of feed
restriction, virus infection, and vitamin injections on plasma concentrations
of B vitamins critical to the immune response were evaluated. Twelve beef steer
calves, 6 to 8 mo of age, were fed below maintenance for 17 d and deprived of
food for 3 d during a 20-d period after weaning. They then were inoculated
intranasally with live attenuated bovine herpesvirus-1 (BHV-1). Six calves
received saline injections and six received injections of a B vitamin mixture
and ascorbate every 48 h for 14 d before and 14 d after inoculation. A mild
respiratory infection developed in all calves 4 to 5 d after inoculation. In
control calves, restricted intake and food deprivation decreased plasma vitamin
B6 and pantothenate and increased vitamin B12 but did not affect folic acid and
ascorbate concentrations. Vitamin injections increased plasma concentrations of
vitamin B6, folic acid, vitamin B12, pantothenic acid, and ascorbate (P <
.002). Plasma concentrations of vitamin B6, vitamin B12, pantothenic acid, and
ascorbate, but not folic acid, were markedly reduced in all calves during the
BHV-1 infection (P = .001). The vitamin B6, pantothenic acid, vitamin B12, and
ascorbate status of stressed calves may affect their immune response to
vaccination or infection.
PMID: 8791209, UI: 96383345

10. Shor-Posner G et al. Impact of vitamin B6 status on psychological distress
in a longitudinal study of HIV-1 infection. Int J Psychiatry Med
1994;24(3):209-22.
          Department of Epidemiology and Public Health, University of
          Miami School of Medicine, FL 33101.
OBJECTIVE: Inadequate vitamin B6 status has been associated with altered
neuropsychiatric function, possibly through its effect on the metabolism of
neurotransmitters, including serotonin (5-HT). The present eighteen month
longitudinal study evaluated the relationship between vitamin B6 status and
psychological distress in HIV-1 infected individuals, controlling for the
influence of negative life events, social support and coping style. METHOD:
Biochemical measurements of nutritional status, and dietary intake evaluations
were obtained in HIV-1 seropositive homosexual men, (at baseline: CDC Stages II
and III, n = 70; Stage IVA, IVC2 n = 18) at six month intervals. Alterations in
nutrient status (e.g., vitamin B6 adequate to inadequate; inadequate to
adequate), were compared with changes in psychological distress, measured by
the Profile of Mood States, using a multiple regression analysis. RESULTS: A
significant decline in psychological distress was demonstrated with
normalization of vitamin B6 status from inadequate to adequate status (p <
0.02). A decrease in psychological distress was also observed with increased
tryptophan intake in subjects who were vitamin B6 adequate (p < 0.02).
CONCLUSIONS: Significant effects for the nutritional variables remained even
when negative life event stressors, social support, and coping style were
controlled, suggesting that vitamin B6 status may be an important co-factor in
determining level of psychological distress over time in HIV-1 infected
individuals. 
PMID: 7890479, UI: 95197351

11. Allgood VE et al. Modulation by vitamin B6 of glucocorticoid
receptor-mediated gene expression requires transcription factors in addition to
the glucocorticoid receptor. J Biol Chem 1993 Oct 5;268(28):20870-6.
          Department of Physiology, University of North Carolina,
          Chapel Hill 27599-7545.
ab: We have investigated the mechanism by which vitamin B6 acts to modulate
steroid hormone-mediated gene expression. We show that the level of
glucocorticoid-induced gene expression from simple promoters, containing only
hormone response elements and a TATA sequence, was not affected by alterations
in intracellular vitamin B6 concentration. However, modulation of
hormone-induced gene expression was restored with the inclusion of a binding
site for the transcription factor nuclear factor 1 (NF1) within the
hormone-responsive promoter; glucocorticoid-induced gene expression was reduced
by 44% under conditions of elevated intracellular vitamin B6 concentration and
enhanced by 98% in mild vitamin deficiency...
PMID: 8407919, UI: 94012628

12. Allgood VE, Cidlowski JA. Vitamin B6 modulates transcriptional activation
by multiple members of the steroid hormone receptor superfamily. J Biol Chem
1992 Feb 25;267(6):3819-24.
     ab: Recent studies have shown that vitamin B6 modulates transcriptional
activation
by the human glucocorticoid receptor in HeLa S3 cells. We have now examined the
possibility that vitamin B6 might similarly influence transcriptional
activation by the glucocorticoid receptor in other cell types, as well as gene
expression mediated by other members of the steroid hormone receptor
superfamily. We show that elevated vitamin B6 concentrations suppress by 40-65%
the level of transcription mediated through the endogenous murine L cell
glucocorticoid receptor, as well as the human receptor transfected into E8.2
and T47D cells. In contrast, glucocorticoid receptor-mediated transcription was
enhanced 60-110% in mild vitamin deficiency. The level of hormone-independent
constitutive gene expression was not affected by these same alterations in
vitamin B6 concentration. These studies indicated that the transcriptional
modulatory effects of the vitamin were neither restricted to specific cell
types nor limited to the human form of the glucocorticoid receptor. We next
determined if hormone-induced transcription by several other steroid receptors
(androgen, progesterone, and estrogen receptors) was analogously affected by
alterations in vitamin B6 concentration. Analysis of gene expression mediated
through the mouse mammary tumor virus promoter revealed that transcriptional
activation of both the androgen and progesterone receptors was reduced by
35-40% under conditions of elevated vitamin B6 and enhanced by 60-90% in
deficiency, again under conditions where constitutive expression was
unaffected. Using a different promoter, the estrogen-regulated vitellogenin
promoter, we found that transcriptional activation of the estrogen receptor was
similarly affected. Estrogen-induced gene expression was reduced by 30% under
conditions of elevated intracellular vitamin B6 and enhanced by 85% in vitamin
deficiency. Thus, vitamin B6 modulates transcriptional activation by multiple
classes of steroid hormone receptors. The similarities in vitamin B6 effects on
transcription mediated through different promoters, the mouse mammary tumor
virus and vitellogenin promoters, suggest that this vitamin may modulate the
expression of a diverse array of hormonally responsive genes. These
observations together support the hypothesis that vitamin B6 represents a
physiological modulator of steroid hormone action.
PMID: 1310983, UI: 92156119

13. Kamata K et al. Water soluble vitamins in patients with chronic renal
failure and effect of B6 administration of immunological activity. Proc Clin
Dial Transplant Forum 1979;9:194-6.
     ab: Blood concentrations of water soluble vitamins were studied in 29
undialyzed
and 35 dialyzed patients with CRF, and 36 healthy volunteers. Effects of B6
administration on immunological parameters were studied in dialyzed patients.
In dialyzed patients, whole blood B1 decreased, while plasma B2, B6 and serum
B12 and folic acid increased. In undialyzed patients with uremia, plasma B2,
serum B12 and folic acid increased, while plasma C decreased in patients with
moderate CRF. Oral administration of B6 for 4 wks was associated with improved
tuberculin skin tests and PHA mitogen responses in dialyzed patients.
Supplementation of B1 is required for patients with CRF while B6 and C may be
considered.
PMID: 552042, UI: 81032493

14. Miller LT et al. The effect of dietary protein on the metabolism of vitamin
B-6 in humans. J Nutr 1985 Dec;115(12):1663-72.
     ab: Eight men, aged 21-31 yr, were fed semipurified diets containing 0.5
(low), 1.0
(medium) and 2.0 (high) g protein/kg body weight; vitamin B-6 intake was kept
constant at 1.6 mg/d. Each level of protein was fed for 15 d. Urinary vitamin
B-6 (UB-6), urinary 4-pyridoxic acid (4-PA), plasma total vitamin B-6 (PB-6)
and plasma pyridoxal 5'-phosphate (PLP) were determined every third day. Means
are reported for all subjects of values determined during the second half of
each period. Concentration of urinary and plasma vitamin B-6 compounds were
negatively correlated with protein intake: the correlation coefficient of
nitrogen intake with 4-PA was -0.69 (P less than 0.01); with PLP, -0.45 (P less
than 0.05); and with PB-6, -0.48 (P less than 0.05). The decrease in UB-6 was
not statistically significant. These results indicate that with increased
intake of dietary protein, vitamin B-6 is retained in the body for increased
catabolism of amino acids. When evaluating vitamin B-6 requirements or status
in humans, protein intake must be considered.
PMID: 4067657, UI: 86061921

15. Fujii A et al. Effect of vitamin B complex on neurotransmission and neurite
outgrowth. Gen Pharmacol 1996 Sep;27(6):995-1000.
     ab: 1. The effect of vitamin B complex (vitamin B1, B6 and B12) was studied
on nerve conduction velocity in acrylamide-neuropathy rats maintained on refined
semisynthetic complete vitamin and vitamin B-deficient diets in vivo and on
neurite outgrowth in vitro using cells obtained from dorsal root ganglions of
mice. 2. Acrylamide neuropathy was clearer in the group maintained on a refined
semisynthetic vitamin B-deficient diet than in those on a refined semisynthetic
complete vitamin diet. The neurotoxicity was lowest in the group given vitamin
B complex prophylactic-therapeutically, next higher following therapeutic
administration and last with no vitamin B complex administration in both groups
maintained on a refined semisynthetic vitamin B-deficient diet and a refined
semisynthetic complete vitamin diet. 3. The nerve conduction velocity tended to
decrease by treatment with acrylamide. The decrement of nerve conduction
velocity was partially inhibited by vitamin B complex. No significant
difference was found in the groups treated with acrylamide and given vitamin B
complex prophylactic-therapeutically and the control (no acrylamide treatment)
in the group maintained on a refined semisynthetic vitamin B-deficient diet. 4.
The greatest neurite outgrowth was found in the group treated with vitamins B1,
B6 and B12-enriched medium, followed by the group of vitamin B12-enriched and
vitamin B1-enriched media. All groups treated with a vitamin B-enriched medium
had significantly greater (P < 0.01) outgrowth than the controls.
PMID: 8909981, UI: 97066500

16. Oertel SH et al. Treatment of Epstein-Barr virus-induced posttransplantation
lymphoproliferative disorder with foscarnet alone in an adult after simultaneous
heart and renal transplantation. Transplantation 1999 Mar 15;67(5):765-7.
17. Drago F et al. Epstein-Barr virus-related primary cutaneous amyloidosis.
Successful treatment with acyclovir and interferon-alpha. Br J Dermatol 1996
Jan;134(1):170-4.
18. Dellemijn PL et al. Successful treatment with ganciclovir of presumed
Epstein-Barr meningo-encephalitis following bone marrow transplant. Bone Marrow
Transplant 1995 Aug;16(2):311-2.
19. Brady M. Epstein-Barr virus infection in children: implications for the
treatment of infectious mononucleosis. J Pediatr Health Care 1994
Sep-Oct;8(5):233-5.
20. Pediatr Radiol 1998 Jul;28(7):489-91 
Cytotoxic T cells and immunotherapy.
Kitchingman GR, Rooney C
Department of Virology and Molecular Biology, St. Jude Children's Research
Hospital, 332 N. Lauderdale St., Memphis, TN 38105, USA.
ab: Promising immunotherapies for viral infections and malignancies reflect the
successful, rapid translation of laboratory findings into clinical practice.
Fletcher et al. [1] present imaging studies of Epstein-Barr virus
(EBV)-associated lymphomas before and after immunotherapy. Here, we briefly
review the scientific bases of such novel therapies, which have evolved from
advances in understanding of immune effector cells, of the cytokines that drive
immune responses, and of the mechanisms underlying cell death.
PMID: 9662564, UI: 98328757