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Biomedical subjects

S Simon

Publications and source records attributed to S Simon.

At least 91 records · Page 5Linked to original sources

Intracellular pH and the control of multidrug resistance.

Many anticancer drugs are classified as either weak bases or molecules whose binding to cellular structures is pH dependent. Accumulation of these drugs within tumor cells should be affected by transmembrane pH gradients. Indeed, development of multidrug resistance (MDR) in tumor cells has been correlated with an alkaline shift of cytosolic pH. To examine the role of pH in drug partitioning, the distribution of two drugs, doxorubicin and daunomycin, was monitored in fibroblasts and myeloma cells. In both cell types the drugs rapidly accumulated within the cells. The highest concentrations were measured in the most acidic compartments--e.g., lysosomes. Modifying the cellular pH in drug-sensitive cells to mimic reported shifts in MDR caused an immediate change in the cellular drug concentration. Drug accumulation was enhanced by acidic shifts and reversed by alkaline shifts. All of these effects were rapid and reversible. These results demonstrate that the alkaline shift observed in MDR is sufficient to prevent the accumulation of chemotherapeutic drugs independent of active drug efflux.

3T3 Cells↗

Antibodies specific for the neuronal form of the Src protein elicited by an antigenized antibody.

To elicit antibodies directed specifically against the neuron-specific form of the c-src gene product, pp60c-src(+), we used an antigenized antibody comprising a decamer containing the amino acid sequence specific to pp60c-src(+) inserted into the third hypervariable loop of the heavy (H)-chain variable (V)-region. This was used to raise anti-idiotype antibodies reacting with the peptide epitope in rabbits. The antisera reacted with pp60c-src(+), as judged by immune blotting, immunoprecipitation, immune complex kinase assay, and indirect immunofluorescence staining, but did not react with the fibroblast form of the c-src gene product, pp60c-src. Antigenized antibody is a useful approach for producing antibodies able to distinguish between isoforms of the same gene product and specific for the neuronal form of the Src protein.

3T3 Cells↗

Interactions of lipopolysaccharide with neutrophils in blood via CD14.

The functional characteristics of neutrophils are exceedingly sensitive to physiological conditions as well as the details of isolation. Exposure to lipopolysaccharide (LPS) or even contamination of the isolating media with traces of LPS is known to play an important role in regulating cell function and expression of receptors. Because of the suspected role of CD14 as a receptor for LPS, we used anti-CD14 monoclonal antibodies both to identify CD14 in the cell surface of polymorphonuclear leukocytes and to inhibit functional changes elicited by LPS. Cytometric techniques were used to investigate the regulation of CD14 and CR3 on the neutrophil cell surface in whole blood to minimize any effects of isolation. In whole blood neutrophil express low levels of formyl peptide receptor, CD14, and CR3, which increase substantially in response to formyl peptide and LPS. The increases in CR3 and CD14 occurred in parallel and were independent of protein synthesis and tumor necrosis factor (TNF) production. The increase in CR3 was inhibited by antibodies MY4, 3C10, and 28C5 against CD14. These findings are consistent with the notion that in blood the observed receptor up-regulation is in direct response to the action of LPS on neutrophils through CD14 and does not require products from macrophages such as TNF or the production of C5a from the plasma.

Antibodies, Monoclonal↗

A constitutively expressed serum amyloid A protein gene (SAA4) is closely linked to, and shares structural similarities with, an acute-phase serum amyloid A protein gene (SAA2).

The acute-phase reactant serum amyloid A (SAA) is a polymorphic apolipoprotein encoded by a family of highly homologous and closely linked genes: SAA1, SAA2, and SAA3. We have isolated a human genomic cosmid clone containing the gene encoding a fourth, constitutively expressed member of the human SAA superfamily, C-SAA, together with an SAA2*2 (SAA2 beta) gene. The gene encoding C-SAA shares the same 5' to 3' orientation as SAA2*2 and has the characteristic four-exon structure of the other members of the SAA superfamily. The exons of the gene encoding C-SAA share only limited sequence identity with those of SAA1, SAA2, and SAA3; they specify an mRNA, represented by the CS-1 cDNA reported previously by us, which is expressed at low levels (relative to the acute-phase SAAs) in normal and acute-phase liver. The gene encoding C-SAA is located 9 kb downstream of SAA2*2 and therefore occupies the locus that has been identified as containing the SAA4 gene.

Acute-Phase Proteins↗

[Information to relatives of organ donors. Factors of consent or refusal. Results of a multicenter study].

The French law on organ harvesting in brain dead patients allows this to be done without the family's consent, but prescribes to inform the relatives. Despite this, most teams do not harvest organs if the family is strongly opposed to the procedure. Information given to the relatives is therefore a very important point in the management of the donor. This prospective multicentre enquiry was designed to assess the conditions in which relatives were informed, and to determine the criteria which improve the rate of consent for the donation. After such information had been given, a questionnaire was filled in and sent to France-Transplant. Two hundred and seven interviews were analysed over an 18-month period. In two thirds of cases, the relatives were interviewed less than three hours after the diagnosis of brain death had been made. A written information sheet was used in only one third of interviews. Information was given by telephone in 11% of cases. Organ donation was accepted, on average, in 74% of cases. This ratio, which did not depend on the hospital, increased with the age of the donor: 66% for donors aged less than 18 years to 86% for those more than 50 years old. The aetiology of brain death was not a factor determining acceptance of the donation. The main factor was the conditions of interview: acceptance rate was the highest when there was a one hour delay between giving the information on the donor's brain death and that concerning organ donation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stability and control of a frontal four-link biped system.

A conceptual model for studying the involvement of the central nervous system (CNS) in the performance of lateral swaying movements is described. The model is based on a four-link planar biped that approximates gross human locomotion in the frontal plane. The viscoelastic function of the musculoskeletal system provides a linear controller for the system. Such an intrinsic controller can effectively duplicate simple well-learned tasks in the absence of higher level CNS feedback. This hypothesis is supported by comparing the proposed controller with two neurophysiologically involved linear decoupling schemes. Reference trajectories for swaying commands are recorded from experiments conducted in the Gait Analysis Laboratory of the Ohio State University Hospitals. These reference trajectories are inputs to all three controllers. The viability of intrinsic feedback scheme in the execution of swaying tasks is demonstrated via comparison of responses from the three controllers.

Central Nervous System↗

[Acute mesenteric vein thrombosis. A rare complication after splenectomy due to autoimmune hemolytic anemia in childhood].

Mesenteric vein thrombosis is a rare but severe complication in children requiring splenectomy. We report on a 5-year-old boy with an autoimmune hemolytic anemia who underwent splenectomy because of severe side effects from cortisone therapy. 10 months after splenectomy he presented with signs of a paralytic ileus. Laparotomy showed mesenteric vein thrombosis with hemorrhagic bowel infarction requiring resection of two thirds of the small intestine. An early recognition and thrombolytic or surgical treatment of mesenteric vein thrombosis may reduce the incidence of hemorrhagic infarction, peritonitis, and secondary complications in these patients.

Anemia, Hemolytic, Autoimmune↗

[Kinetics of thermal killing of microorganisms in egg yolk].

Egg yolk is relating to its germ content and enzyme activity only restricted storable. Unpasteurized egg yolk get spoiled between a few hours and days. The rapid spoilage can be reduced by a pasteurization and following cold storage. The storage stability of egg yolk can be increased by additives, e.g. salt or saccharose. Kinetic results of the thermal microorganisms destruction in the egg yolk with and without stabilizing additives are presented in this article. It will be shown that the evaluation method from REICHART gives representative results for mixed cultures, too. A further evaluation method by a differential equation will be demonstrated and discussed.

Bacteria↗

The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer--Genitourinary Group.

The prognostic value of the pathological response to combination chemotherapy of deeply invasive transitional cell cancer of the bladder was retrospectively assessed in 147 patients. Data were collected from 8 different centers. Patients were eligible if they had received intravenous combination chemotherapy followed by partial, total or radical cystectomy, and if they had a minimum followup of 2 years after the start of chemotherapy. Of the patients 90% received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) or cisplatin plus methotrexate for a median of 3 courses (range 1 to 6). Of the 83 patients who were alive at analysis actuarial median followup was 30.5 months (range 13.2 to 85.6 months). A major pathological response (stage P0, Pis, Pa or P1) was achieved in 41.5% of the patients. Patients with a major pathological response (p stage less than 2) had a 5-year survival of 75% in contrast to 20% for the remaining nonresponding patients (p stage 2 or more). The survival of patients with a major pathological response was independent of whether the response was induced by 2 or more courses of chemotherapy, or whether it was induced by M-VAC in comparison with cisplatin plus methotrexate. Preoperative clinical assessments can identify nonresponding patients correctly and in these cases alternative treatment programs are required, since 80% will die of the disease. Moreover, if neoadjuvant chemotherapy is proved to increase survival, the data emphasize the importance of the response rate of the primary tumor and the need to investigate the optimal number of courses to induce the best response, preferably in the individual patient.

Actuarial Analysis↗

[Techniques and experiences in funnel chest operations].

Hegemann's technique of funnel chest correction using transsternal metal bar stabilization was adapted from the method published by Sulamaa and coworkers in 1958. Until the end of 1991, about 2400 chest wall corrections were performed in our department, more than 2000 of them using modifications of the original method. The principles of external chest wall measurement, our classification method, and the current operative modifications are described. In long-term follow-up examinations less than 3% recurrences should be possible.

Adolescent↗

A restriction fragment of the C2 gene is a unique marker for C2 deficiency and the uncommon C2 allele C2*B (a marker for type 1 diabetes).

There are three common C2 protein alleles in caucasians, C2*C, C2*B, and C2*Q0, with allele frequencies of 0.96, 0.03, and 0.01, as well as Sst I RFLP variants of 2.75, 2.7, 2.65, 2.55, and 2.4 kb, with frequencies of 0.017, 0.533, 0.358, 0.017, and 0.075. Thus, C2*C is informatively split by the RFLP. Of 94 nonrandomly ascertained caucasian complotypes, 77 contained C2*C, four contained C2*Q0, and 13 had C2*B. None of the C2*C-containing complotypes carried the 2.75 kb Sst I fragment and all of the complotypes with C2*B or C2*Q0 carried it. All of the C2*Q0 alleles were associated with C4A*4, C4B*2 in the complotype S042 as previously reported. C2*B was usually (9/13) in the complotype SB42, occasionally (1/13 each) in SB45, SB41, SB(4,3)0, and SB31. Thus, the association of the C2 2.75-kb fragment was with C2*B and C2*Q0, not with C4A*4, C4B*2, or even C4A*4 alone. The complotype SC42 was associated with the 2.65-kb Sst I fragment in four of five instances and in a single example with the 2.7-kb fragment. C2*B and C2*Q0 possibly had a common evolutionary ancestor complotype which carried the 2.75-kb Sst I fragment, and BF*S, C4A*4, and C4B*2. C2*B (particularly as the haplotype HLA-Bw62, SB42, DR4) is associated with type 1 diabetes but C2*Q0 is protective.

Alleles↗

A survey of the nutritional adequacy of meals served and eaten by patients.

The survey was carried out at one hospital to evaluate the nutrient content of the food served to and consumed by eight female patients. A weighed food intake was undertaken on the subjects chosen, over three days. Observations were also recorded regarding the nursing and catering practices relating to meals. The results showed that the food served to this group of patients was deficient in energy, folic acid, iron and vitamin D and that this group of patients failed to achieve an adequate vitamin C, protein, calcium and fibre intake. Problems also existed with the ordering and service procedure for meals, timing of meals, quantities of food delivered to the ward and procedure of patients who are eating poorly. Although the numbers in the survey were too small for statistical analysis, it was felt that the results were as representative as possible. This survey was felt to be very worthwhile and highlighted the need for all members of staff involved in the care of these patients to work together to consider ways that the patients' food intake could be improved in the future. The study, carried out by a dietitian is particularly relevant to the work of nurses in this field, as they are often the key persons affecting the patient's choice and consumption of food.

Female↗