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21.
L Patel PE Clayton ME Jenney JE Ferguson TJ David 《Archives of disease in childhood》1997,76(6):505-508
Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible. 相似文献
22.
Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells 总被引:7,自引:5,他引:7
Cell to cell communication via gap junctions is essential in the
maintenance of the homeostatic balance of multicellular organisms. Aberrant
intercellular gap junctional communication (GJIC) has been implicated in
tumor promotion, neuropathy and teratogenesis. Oxidative stress has also
been implicated in similar pathologies such as cancer. We report a
potential link between oxidative stress and GJIC. Hydrogen peroxide, a
known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells
with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible
as indicated by the complete recovery of GJIC with the removal of H2O2 via
a change of fresh media. Free radical scavengers, such as t-butyl alcohol,
propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2,
which indicated that the effects of H2O2 on GJIC was probably not a
consequence of aqueous free radical damage. The depletion of intracellular
GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of
glutathione- sufficient cells with H2O2 resulted in the
hyperphosphorylation of connexin43, which is the basic subunit of the
hexameric gap junction protein, as determined by Western blot analysis.
TPA, a well-known tumor promoter, also inhibits GJIC via
hyperphosphorylation of GJIC, which is a result of protein kinase-C
activation. However, H2O2 also induced hyperphosphorylation in
GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism
of GJIC inhibition must be different from the TPA-pathway and involves GSH.
相似文献
23.
Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon 总被引:1,自引:1,他引:1
We have examined whether dietary polyamines influence the formation and
initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in
rat colon. Effects of a combination of dietary polyamines at three dose
levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g;
spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied
in animals in two different experimental situations: animals treated with
AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a
specific inhibitor of endogenous polyamine synthesis. In both experimental
situations, dietary polyamines enhanced the growth of ACF, expressed as the
number of large ACF (foci with three or more aberrant crypts, ACF > or =
3), whereas the formation of ACF, expressed as the number of ACF, was
apparently not altered. In animals treated with AOM alone, maximal growth
enhancing effect on ACF was nearly obtained with the median level of
dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO
reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of
DFMO was counteracted by dietary polyamines in a dose- dependent manner,
and it was abolished at the highest level of polyamines. In conclusion, it
was demonstrated that dietary polyamines are able to enhance the growth of
AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused
inhibition of ACF growth, probably by compensating for the DFMO-reduced
endogenous polyamine synthesis.
相似文献
24.
Hansen LA; Malarkey DE; Wilkinson JE; Rosenberg M; Woychik RE; Tennant RW 《Carcinogenesis》1998,19(10):1837-1845
We previously reported that papillomas can arise from the follicular
epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow
mutation (A(vy)) of the mouse agouti gene which regulates coat color
pigmentation by acting within the micro-environment of the hair follicle
has been shown to function as a tumor promoter in the liver, we
hypothesized that it may also play a role in TGxAC skin tumorigenesis.
Endogenous agouti protein product was detected in the outer root sheath of
anagen hair follicles following plucking of the hair shaft, but not in the
interfollicular epithelium, in TGxAC mice on an FVB/N genetic background.
It was also detected in papillomas from these mice produced by
12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking.
Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line
results in an approximately 2-fold increase in papilloma development
compared with controls which did not carry the A(vy) allele following
twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition,
TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but
not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of
humoral hypercalcemia mediated by parathyroid hormone-related protein
(PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus,
we conclude that the A(vy) allele can influence the development of skin
tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic
TGxAC mice.
相似文献
25.
26.
Jane L Roberts Laurence Booth Adam Conley Nichola Cruickshanks Mark Malkin Rakesh C Kukreja Steven Grant Andrew Poklepovic Paul Dent 《Cancer biology & therapy》2014,15(6):758-767
We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease. 相似文献
27.
Cortisol catabolism by lymphocytes of patients with systemic lupus erythematosus and rheumatoid arthritis 总被引:2,自引:0,他引:2
We have shown that low cortisol catabolism by lymphocytes correlates with a high sensitivity of the cells to the steroid. In the present study, we aimed to assess whether high resistance to corticosteroid treatment correlates with a high rate of cortisol catabolism by lymphocytes. Since patients with systemic lupus erythematosus (SLE) usually require high doses of corticosteroids, while patients with rheumatoid arthritis (RA) respond to relatively low doses of steroids, we compared the capability of lymphocytes of patients with SLE and RA to catabolize cortisol. The rate of cortisol catabolism obtained with the RA group was not significantly different from that obtained with the control group. The catabolism of cortisol by lymphocytes of the SLE group was significantly higher than both the control group (p less than 0.05) and the RA group (p less than 0.01). A significant correlation was demonstrated between the SLE disease activity index and rates of cortisol catabolism attained by lymphocytes of SLE patients (p less than 0.001). 相似文献
28.
The efficacy and outcome of bone marrow transplantation therapy following lethal irradiation were examined in syngeneic mice that had a hereditary macrocytic anemia (an/an) or were genotypically normal (+/+). Successful RBC and WBC replacement, based on blood cell parameters and donor genetic markers, were observed in all combinations of transplant therapy. Nevertheless, the an/an mice died prematurely several months after treatment, whether they received +/+ or an/an marrow cells. In contrast, the +/+ recipients of either +/+ or an/an marrow cells survived for at least 1 year after transplantation. Premature death of the an/an mice was associated with lymphopenia, anemia, kidney lesions, and severe pathogen-free pneumonitis. On the basis of our results, we hypothesize that the premature deaths of an/an mice are caused by a kind of chronic irradiation damage to which an/an mice are especially susceptible. 相似文献
29.
The widespread assumption that cytoplasts generated from human polymorphonuclear leukocytes (PMNs) are vesicles consisting solely of cytoplasm surrounded by plasma membrane and devoid of granule activity remains to be tested. PMN cytoplasts were prepared by centrifugation of intact cells on a Ficoll step gradient in the presence of cytochalasin B. Two granule membrane markers, Mol, a fluorometrically detectable antigen, and cytochrome b, both of which have been shown to translocate to the plasma membrane during granule release, were compared for their activity in cytoplasts and intact PMNs. We found that the amount of Mol detected on the plasma membrane of intact PMNs, as compared with other membrane markers (such as antigens LFA-1 and beta 2m), increased 1.6- fold upon exposure of PMNs to Ficoll plus cytochalasin B prior to centrifugation. Another twofold increase in Mol expression occurred upon cytoplast preparation. Release of the granule enzymes, vitamin B12- binding protein, and lysozyme were also followed and correlated well (r = .78 and .92) with the amount of Mol antigen present on the cell surface. Cytochrome b was also found to be higher (1.4-fold) on plasma membranes isolated from cytoplasts than on plasma membranes isolated from intact control cells. These results indicate that some fusion of granule membranes and plasma membranes occurred during treatment of PMNs with Ficoll plus cytochalasin b and during cytoplast preparation. 相似文献
30.
Talmadge JE; Schneider M; Keller J; Ruscetti F; Longo D; Pennington R; Bowersox O; Tribble H 《Blood》1989,73(6):1458-1467
In a series of studies designed to extend our understanding of interleukin-2 (IL-2) and to study the effect of biologic response modifiers on bone marrow, we observed that administering recombinant human (rH) IL-2 to normal mice resulted in an increase in the frequency of colony-forming units-culture (CFU-C) in bone marrow. In addition, rH IL-2 was able to accelerate host recovery from cyclophosphamide (CTX)- or radiation-induced bone marrow depression and peripheral blood leukopenia. Not only can rH IL-2 accelerate, in a dose-dependent manner, the return of bone marrow, peripheral blood cellularity, and CFU-C frequency to normal levels following cytoreduction by CTX or irradiation, but it also significantly increases CFU-C frequency to greater than normal levels. Furthermore, rH IL-2 can significantly prolong survival of animals receiving a lethal dose of irradiation or CTX. Thus, multiple mechanisms are responsible for the synergistic therapeutic activity associated with rH IL-2 and CTX. rH IL-2 does not act only as an immunomodulatory agent in the presence or absence of suppressor T cells, but also accelerates host recovery from cytoreductive agents, resulting in decreased leukopenia and perhaps resistances to secondary infection. Thus, rH IL-2 plus chemotherapy may increase therapeutic activity against neoplastic disease, not only by adding immune stimulation to the direct antitumor effect of the drug but also by allowing delivery of higher, more effective doses of chemotherapy. 相似文献