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Biomedical subjects

S Salmon

Publications and source records attributed to S Salmon.

At least 19 recordsLinked to original sources
PubMed2004

From arteriographies to computational flow in saccular aneurisms: the INRIA experience.

Saccular aneurisms illustrate usefulness and possible techniques of image-based modeling of flow in diseased vessels. Aneurism flow is investigated in order to estimate the rupture risk, assuming that the pressure is the major factor and that high-pressure zones are correlated to within-wall strong-stress concentrations. Computational flow is also aimed at providing additional arguments for the treatment strategy. Angiographies of aneurismal vessels of large and medium size are processed to provide three-dimensional reconstruction of the vessel region of interest. Different reconstruction techniques are used for a side and a terminal aneurisms. Reconstruction techniques may lead to different geometries especially with poor input data. The associated facetisation is improved to get a computation-adapted surface triangulation, after a treatment of vessel ends and mesh adaptation. Once the volumic mesh is obtained, the pulsatile flow of an incompressible Newtonian blood is computed using in vivo non-invasive flowmetry and the finite element method. High pressure zones are observed in the aneurism cavity. The pressure magnitude in the aneurism, the location and the size of high pressure zones depend mainly on the aneurism implantation on the vessel wall and its orientation with respect to the blood flux in the upstream vessel. The stronger the blood impacts on the aneurismal wall the higher the pressure. The state of the aneurism neck, where a high-pressure zone can occur, and the location of the aneurism, with an easy access or not, give arguments for the choice between coiling and surgical clipping. Mesh size and 3D reconstruction procedure affect the numerical results. Helpful qualitative data are provided rather than accurate quantitative results in the context of multimodeling.

Angiography↗
PubMed2001

Innovative approaches to comprehensive cardiovascular disease risk reduction in clinical and community-based settings.

We have developed, tested, and successfully implemented an affordable, evidence-based, comprehensive cardiovascular disease risk-reduction program for use in primary and secondary prevention settings. The program is administered at hospitals, physician practices, cardiac rehabilitation programs, work sites, shopping malls, and health clubs. The program is also delivered from a call center using the telephone and the Internet. Program staff are guided by a computerized participant management and tracking system. Lifestyle management interventions are based on several behavior change models, primarily social learning theory, the stages of change model, and single concept learning theory. Typically, the program is administered entirely by non-physician healthcare professionals whose services are integrated with the care provided by the participants' physicians. Outcome data have documented the clinical effectiveness of this innovative approach.

Adaptation, Psychological↗
PubMed2000

Chromosome abnormalities in malignant melanoma: clinical significance of nonrandom chromosome abnormalities in 206 cases.

We report the cytogenetic abnormalities from a series of 206 primary malignant melanoma specimens referred to a single institution. A total of 169 out of 206 unique cases had chromosome breakpoints. A previously described statistical method was used to detect nonrandom distribution of chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints (indicating that the observed number of breaks significantly exceeded the expected number of breaks) was detected in 28 regions, suggesting a hierarchy of genetic abnormalities in melanoma. Clinical variables and tumor characteristics were analyzed for associations with the presence of any nonrandom chromosome breakpoints; with individual, nonrandomly involved chromosome regions; and with paired, nonrandomly involved chromosome regions. No nonrandomly involved chromosome regions or pairs of regions appeared to significantly affect survival. These results identify recurring, nonrandom chromosome abnormalities in malignant melanoma. These results suggest that recurring, nonrandom chromosome alterations play a key role in the etiology and/or progression of malignant melanoma and identify targets within the genome for molecular genetic studies.

Chromosome Aberrations↗
PubMed2000

Contrasting effects of excess ferritin expression on the iron-mediated oxidative stress induced by tert-butyl hydroperoxide or ultraviolet-A in human fibroblasts and keratinocytes.

Iron and/or ferritin accumulation are known to occur under pathological conditions in many inflammatory skin diseases or in human skin chronically exposed to UV light. Under such conditions, ferritin is believed to play an effective protective role in accommodating and 'deactivating' excess 'free' iron produced by the inflammatory process or the UV illumination. The present study compares the relationship between ferritin over-expression and effects of an oxidative stress induced chemically by tert-butyl hydroperoxide or photochemically by UV-A radiation. As shown by immunoassay, cultured MRC 5 and HS 68 fibroblasts treated for at least one day with transferrin or overnight with non-toxic concentrations of the ferric nitrilotriacetate complex express up to 10 times more ferritin than untreated cells, whereas a five-fold increase is obtained with NCTC 2544 keratinocytes. In all cases a parallel increase in soluble cellular iron is measured by inductive plasma emission spectroscopy. The superoxide dismutase and catalase activities and total glutathione levels are not modified by the iron treatment, whereas a transient increase in the Se-dependent glutathione peroxidase activity of keratinocytes is observed after a short incubation with the iron complex. In keratinocytes and fibroblasts, ferritin over-expression after iron treatment markedly inhibits lipid peroxidation but, paradoxically, not the mortality induced by tert-butyl hydroperoxide. In contrast, this excess ferritin does not protect cells from both the peroxidation and mortality induced by moderate doses (30 J/cm2) of UV-A radiation. As a consequence, protection against oxidative damage by excess ferritin synthesis clearly depends on the nature of the oxidative stress on cell targets and it seems to be of lesser importance in the case of photochemically induced oxidation.

Catalase↗
PubMed2000

Telemedicine use in two nurse-led minor injuries units.

Telemedicine links were established between two nurse-led minor injuries units (MIUs) located in community hospitals and an accident and emergency department in a district general hospital. Telemedicine consultations were logged. During the first year of operation, telemedicine use was surprisingly constant, there being an average of 36 calls a month from one MIU and 16 from the other. Possible reasons for this include the clinical protocols under which nurses could refer patients to hospital. The average duration of teleconsultations was 3.5 min. Although the MIUs dealt with roughly similar numbers of patients, approximately 600-700 per month, the proportion for whom telemedicine was used was very different, at 5.2% and 2.3%.

Humans↗
PubMed1999

The major vault protein (MVP), a new multidrug resistance associated protein, is frequently expressed in multiple myeloma.

The major vault protein (MVP), a ribonucleoprotein complex which mediates the transport of xenobiotic toxins, has been implicated in multidrug resistance (MDR) not mediated by p-glycoprotein (P-gp) or multidrug resistance related protein (MRP). We evaluated, via immunohistochemistry, the presence of MVP in plasma cells of myeloma patients. Among 73 patients registered with the Southwest Oncology Group (SWOG), 52 patients (74%) were positive for MVP. The presence of MVP and P-gp were significantly associated (p < 0.01). A univariate analysis of response versus MVP positivity showed borderline statistical significance (p = 0.043) with no association with OS or PFS. In particular, MVP positivity at first biopsy was associated with non-responsiveness to therapy (7/7 patients, 100%). MRP was not present in any of 23 samples tested. An increased proliferative rate (Ki-67 > 5%) was significantly associated with shorter OS (log rank p-value = 0.0002). The collective work indicates that MVP protein is common and abundant in myeloma with potential relevance to therapeutic response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Sensitization of skin fibroblasts to UVA by excess iron.

Human skin chronically exposed to UV light is known to accumulate iron and to have an increased ferritin content as compared to unexposed areas. Iron accumulation is also found in many inflammatory skin diseases. Cultured human fibroblasts loaded with iron by incubation with non-toxic concentrations of the ferric nitrilotriacetate complex have been irradiated with low (up to 15 J/cm2) and moderate (up to 45 J/cm2) UVA doses. At low irradiation doses, lipid peroxidation doubles without affecting the viability of iron-loaded cells. At higher irradiation doses (30 J/cm2) the photocytotoxicity of UVA towards iron-loaded cells increases in a concentration-dependent manner with the iron load. Thus, after exposure to 30 J/cm2 of UVA, the cytotoxicity is about 3-fold greater for cells incubated for 75 min with 100 microM of the ferric complex as compared to those not treated with the ferric complex. Incubation with desferrioxamine, an extremely efficient chelator of ferric ion or vitamin E, a radical scavenger which blocks the lipid peroxidation radical chain, leads to marked inhibition of the sensitizing effects of iron on lipid peroxidation but is less effective for the survival of cells exposed to UVA. A similar concentration-dependent protective effect of desferrioxamine was observed with cultured fibroblasts not treated with the ferric complex. It is suggested that the photoreduction of ferritin and/or other iron-containing proteins plays a significant role in the UVA-induced photocytotoxicity of skin fibroblasts.

Cell Survival↗
PubMed1997

Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma.

Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response (CR) rates and extended disease control. "Total Therapy" (TT) consisting of noncross-resistant induction regimens, followed by a double autotransplant (AT) procedure, was administered to 123 untreated patients with symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3 million units [MU]/m2 subcutaneously thrice weekly) was given until disease recurrence/progression. Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group (SWOG) trials. One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features. TT induced CR in 40% of all 123 patients (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related complications. With a median follow-up of 31 months, median durations of event-free survival (EFS) and overall survival (OS) are 49 and 62+ months, respectively. Abnormalities of chromosomes 11q and 13 were associated with inferior outcome, whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to ST, dose intensification with double AT markedly augments tumor cytoreduction, effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM.

Aged↗
PubMed1997

Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues.

PURPOSE: Studies were conducted on oryzalin (3,5-dinitro-N,N-di(n-propyl)sulfanilamide), a widely used dinitroaniline sulfonamide herbicide, which was identified from plant extracts as an inhibitor of mitogen- and growth factor-mediated intracellular free Ca2+ ([Ca2+]i) signalling in mammalian cells. METHODS AND RESULTS: Oryzalin inhibited vasopressin, bradykinin and platelet-derived growth factor [Ca2+]i signalling in Swiss 3T3 fibroblasts with IC50 values of 14, 16 and 18 microM, respectively. 45Ca2+ uptake into nonmitochondrial stores of saponin-permeabilized Swiss 3T3 cells was inhibited by oryzalin with an IC50 of 34 microM. Oryzalin inhibited colony formation of HT-29 colon carcinoma cells with an IC50 of 8 microM and inhibited the growth of a number of other cancer cell lines and primary human tumors in vitro with IC50 values in the range 3 to 22 microM. A number of oryzalin analogues were studied and an association was found between the ability to inhibit [Ca2+]i signalling and inhibition of the growth of HT-29 human colon cancer cells (P = 0.001) and of CCRF-CEM human leukemia cells (P = 0.016). Oryzalin at doses up to 600 mg/kg administered orally or subcutaneously daily to mice for 3 to 10 days beginning a day after tumor inoculation inhibited the growth of murine B16 melanoma by 63% but showed no appreciable activity when administered subcutaneously or intraperitoneally to mice beginning a number of days after tumor inoculation against a variety of human tumor xenografts. The peak plasma concentration of oryzalin following repeated subcutaneous administration of oryzalin at 600 mg/kg per day to mice was 37 microM and of its major metabolite N-depropyl oryzalin was 53 microM. CONCLUSION: It is unlikely that the absence of significant antitumor activity of oryzalin is a result of the inability to achieve adequate plasma concentrations.

3T3 Cells↗
PubMed1996

Alteration of lipoproteins of suction blister fluid by UV radiation.

Suction blister fluid is a good representative of the interstitial fluid feeding the epidermal cells. Lipoproteins contained in the suction blister fluid of healthy volunteers are readily photo-oxidized by UV radiation in the wavelength range 290-385 nm. Absorbed light doses equivalent to one minimal erythemal dose absorbed by skin exposed to UVB (e.g. 290-320 nm) are sufficient to induce lipid peroxidation and modification of apolipoproteins A-I, A-II and B. Albumin, which is known to protect serum fully from oxidative stresses, is not so effective against photo-oxidation. Although tryptophan (Trp) residues of proteins contained in the suction blister fluid are photo-oxidized, apolipoprotein A-II, which does not contain any chromophoric Trp residue, is also altered by the UV radiation. With regard to results obtained with a model reconstituted fluid, it is suggested that the radical chain reaction of the lipid peroxidation can transfer the initial photodamage at sites not directly susceptible to photo-oxidation. The biological implications of these results are discussed.

Apolipoprotein A-I↗
PubMed1994

Peroxidation of model lipoprotein solutions sensitized by photoreduction of ferritin by 365 nm radiation.

A mechanistic study involving the 365 nm irradiation of aerated, phosphate-buffered solutions of human high-density lipoproteins (HDL3 fraction) and ferritin was undertaken. The 365 nm irradiation of phosphate-buffered horse spleen ferritin solutions induces the release of Fe2+ in the medium. The initial quantum yield of Fe2+ release on irradiation is 0.002. This quantum yield is oxygen independent. The 365 nm irradiation of mixtures of HDL and ferritin leads to alterations in apolipoproteins as revealed by tryptophan (Trp) oxidation and electrophoretic pattern modification. In parallel with protein damage, lipid peroxidation is induced as shown by hydroperoxide and thiobarbituric acid reactive substances (TBARS) formation. These peroxidations are strongly reduced in 0.1 M formate solution, which suggests chain initiation by .OH radicals or subsequent radicals produced by .OH. They are completely inhibited by desferrioxamine, consistent with propagation by Fe2+ ion. By contrast incubation of HDL in the presence of ferritin and FeSO4 induces only poor auto-oxidation. The biological relevance of this study is discussed.

Animals↗
PubMed1993

Copper- and malondialdehyde-induced modification of high density lipoprotein and parallel loss of lecithin cholesterol acyltransferase activation.

Incubation of high density lipoproteins (HDL) with 0.1-10 microM copper ions resulted in a decrease in tryptophan residues and a moderate diminution of lysine residues. Polymerization of apolipoprotein AI (apo A-I) was only observed for the highest concentration of Cu2+. A dose-dependent loss in lecithin cholesterol acyl-transferase (LCAT) activity was noted. Following incubation with 10 mM malondialdehyde, the physicochemical properties of HDL were more pronouncedly affected, in terms of lipid peroxidation products, relative electrophoretic mobility and percentages of intact tryptophan and lysine residues. Polymerization of apo A-I occurred after 40 min incubation, and a time-dependent loss of LCAT activation was noted. Since the deficiency in LCAT activation was observed in relatively mild conditions, when no perturbation of the physico-chemical properties of the particle could be shown, the determination of LCAT activity appears to be a sensitive test for HDL discrete modification.

Apolipoprotein A-I↗
PubMed1993

Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia.

PURPOSE: To determine the toxicities and maximum-tolerated dose of cyclosporine (CsA) administered with daunorubicin as a modulator of multidrug resistance (MDR) in acute leukemia, and to evaluate response to treatment and its relationship to mdr1 gene expression. PATIENTS AND METHODS: Patients with poor-risk acute myeloid leukemia (AML) received sequential treatment with cytarabine (3 g/m2/d intravenously [i.v.]) days 1 to 5, and daunorubicin (45 mg/m2/d) plus CsA as a 72-hour continuous infusion (CI) days 6 through 8 in a phase I/II trial. A loading dose of CsA administered over 1 to 2 hours preceded the CI. CsA dose escalations ranged from 1.4 to 6 mg/kg (load) and 1.5 to 20 mg/kg/d (CI). Whole-blood concentrations of CsA were monitored by immunoassay; plasma concentration of daunorubicin and daunorubicinol were determined by high-pressure liquid chromatography (HPLC). Specimens were analyzed for P-glycoprotein expression, and results confirmed by a quantitative RNA polymerase chain reaction (PCR) assay for the mdr1 gene transcript. RESULTS: Forty-two patients are assessable for toxicity and response. P-glycoprotein was detected in 70% of cases. Dose-dependent CsA toxicities included nausea and vomiting (22%), hypomagnesemia (61%), burning dysesthesias (21%), and prolongation of myelosuppression. Transient hyperbilirubinemia developed in 62% of treatment courses and was CsA-dose-dependent. Reversible azotemia occurred in three patients receiving concurrent treatment with potentially nephrotoxic antibiotics. Steady-state blood concentrations of CsA > or = 1,500 ng/mL were achieved in all patients receiving CI doses > or = 16 mg/kg/d. Mean plasma daunorubicin, but not daunorubicinol, levels were significantly elevated in patients who developed hyperbilirubinemia (P = .017). Twenty-six (62%) patients achieved a complete remission (CR) or restored chronic phase and three patients achieved a partial remission (PR) for an overall response rate of 69% (95% confidence interval, 54% to 84%). The response rate was higher in patients who developed hyperbilirubinemia (P = .001), whereas MDR phenotype did not influence response to treatment. Among five patients with MDR-positive leukemia, cellular mdr1 mRNA decreased (n = 1) or was absent from relapsed specimens (n = 4), while mdr1 RNA remained undetectable at relapse in two patients who were MDR-negative before treatment. CONCLUSION: High doses of CsA, which achieve blood concentrations capable of reversing P-glycoprotein-mediated anthracycline resistance in vitro, can be incorporated into induction regimens with acceptable nonhematologic toxicity. Transient hyperbilirubinemia occurs commonly with CsA administration and may alter daunorubicin pharmacokinetics. Recommended doses of CsA for phase II and III trials are a load of 6 mg/kg and CI of 16 mg/kg/d.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Modified apolipoprotein pattern after irradiation of human high-density lipoproteins by ultraviolet B.

The ultraviolet B-induced destruction of tryptophan residues and lipid peroxidation of high-density lipoproteins is accompanied by the immediate and marked structural modification of the apolipoproteins, as revealed by SDS-polyacrylamide gel electrophoresis and immunoblot with specific monoclonal antibodies. Formation of several polymers of apolipoprotein A-I, apolipoprotein A-II or both apolipoproteins occurred, although apolipoprotein A-II did not contain any Trp residue. These results suggest that initial photochemical damage can be transferred via intramacromolecular processes to other sites within the same apolipoprotein and by intermacromolecular reactions from apolipoprotein A-I to other apolipoproteins. In both cases, lipid peroxidation enhances the propagation of the initial photochemical damage. The physiological significance of this work is discussed with respect to the low-light doses required for the alterations of the high-density lipoproteins.

Apolipoprotein A-I↗