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Biomedical subjects

F Lehmann

Publications and source records attributed to F Lehmann.

At least 19 recordsLinked to original sources
PubMed1998

Cytotoxicity of 35 dental resin composite monomers/additives in permanent 3T3 and three human primary fibroblast cultures.

It was the purpose of this investigation to determine the cytotoxic effects (ED50 concentrations) of 35 monomers or additives identified in commercial dental resin composites. Monolayers of permanent 3T3 cells and three primary human fibroblast types derived from oral tissues (gingiva, pulp, and periodontal ligament) were used as test systems. All substances were tested in concentrations ranging from 0.01 to 5.0 mM. In general, ED50 values varied from 0.06 to > 5 mM. Within the groups of co(monomers), initiators, and cointiators, severe (e.g., Bis-GMA, UDMA, DMBZ, and DMDTA) or moderate (HEMA, BEMA, CQ, DMPT, and DMAPE) cytotoxic effects could be evaluated. Within the group of reaction/decomposition products, only moderate or slight effects were found (ED50: 0.7 to > 5 mM). The inhibitor BHT, the contaminant TPSb, and the photostabilizer HMBP, however, were highly cytotoxic in all cell cultures. In addition, the ED50 values of DBPO and HMBP significantly varied (0.43-3.8 mM, respectively, and 0.44-3.07 mM) with the applied cell culture. Our comprehensive screening shows that for several of the highly cytotoxic composite components, less cytotoxic alternatives are available. Furthermore, there was no cell type identified which was consistently less or more sensitive to the toxic effects of the tested compounds than the others. Primary human periodontal ligament and pulp fibroblasts, however, were found to be more sensitive than 3T3 and gingival fibroblasts to alterations from most tested substances.

3T3 Cells↗
PubMed1997

Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor.

Melanoma lines MEL.A and MEL.B were derived from metastases removed from patient LB33 in 1988 and 1993, respectively. The MEL.A cells express several antigens recognized by autologous cytolytic T lymphocytes (CTL) on HLA class I molecules. The MEL.B cells have lost expression of all class I molecules except for HLA-A24. By stimulating autologous lymphocytes with MEL.B, we obtained an HLA-A24-restricted CTL clone that lysed these cells. A novel gene, PRAME, encodes the antigen. It is expressed in a large proportion of tumors and also in some normal tissues, albeit at a lower level. Surprisingly, the CTL failed to lyse MEL.A, even though these cells expressed the gene PRAME. The CTL expresses an NK inhibitory receptor that inhibits its lytic activity upon interaction with HLA-Cw7 molecules, which are present on MEL.A cells and not on MEL.B. Such CTL, active against tumor cells showing partial HLA loss, may constitute an intermediate line of anti-tumor defense between the CTL, which recognize highly specific tumor antigens, and the NK cells, which recognize HLA loss variants.

Amino Acid Sequence↗
PubMed1997

Vertebral compression fractures in multiple myeloma. Part II. Assessment of fracture risk with MR imaging of spinal bone marrow.

PURPOSE: To determine the utility of bone marrow magnetic resonance (MR) imaging in the assessment of risk of vertebral compression fractures in patients with multiple myeloma. MATERIALS AND METHODS: In 50 patients with stage III multiple myeloma, 280 MR examinations of the thoracolumbar spine obtained at diagnosis and during treatment (mean follow-up, 28 months) were analyzed to determine MR patterns of bone marrow involvement before treatment and the occurrence of vertebral compression fracture at follow-up. Four MR patterns of marrow involvement were determined: A, normal marrow appearance; B, fewer than 10 focal lesions; C, more than 10 focal lesions; and D, diffuse infiltration. Fracture-free survival was compared according to these patterns. RESULTS: During follow-up, 131 vertebral compression fractures appeared in 37 patients. Patients with pattern A (n = 10) or B (n = 16) had significantly longer fracture-free survival before occurrence of the first, second, and third fractures than those with pattern C or D (P < 10(-5)). Relative risks of first, second, and third fracture occurrence for patients with pattern C or D compared with those with pattern A or B were 6.2, 9.1, and 11.0, respectively. CONCLUSION: Determination of MR patterns of spinal bone marrow involvement is a potential relevant factor to predict the risk of vertebral fractures in patients with stage III multiple myeloma.

Adult↗
PubMed1996

Assessment of depth of midazolam sedation using objective parameters.

OBJECTIVE: To determine the relationship between the clinically evaluated depth of midazolam-induced sedation and the cardiac beat-to-beat variability (RR variability) in ICU patients in the intensive care unit (ICU). DESIGN: Prospective study. SETTING: ICU of a university hospital. PATIENTS: 20 consecutive patients studied during weaning from mechanical ventilation and withdrawal of midazolam-induced sedation. MEASUREMENTS AND RESULTS: After clinical evaluation of depth of sedation according to the Ramsay sedation score, the RR variability over 512 RR intervals and predominant respiratory rate were measured. The power spectrum of RR variability was calculated by a fast Fourier transformation and the resulting total frequency band (0.016-0.35 Hz) was subdivided into a very low, a low, and a high frequency band. Stepwise multiple regression analysis in the first 10 patients (group 1) showed a significant relationship between depth of sedation and measures of RR variability combined with respiratory rate (r2 = 0.59; F = 12.1; p < 0.001). The more effective sedation was, the more depressed were both RR variability and predominant respiratory rate. Mean heart rate, mean respiratory rate, median deviation of RR intervals from the mean, and the ratio between spectral power density in the high and the low frequency bands proved to be the most important predictors of the Ramsay score (+/-1 level accuracy: 87%, p < 0.001). Using this regression equation, the Ramsay score was predicted in the remaining 10 patients (group 2) with a +/-1 level of accuracy of 81% (p < 0.001). CONCLUSION: In ICU patients, a significant correlation is found between the depth of midazolam-induced sedation as assessed by the Ramsay sedation score and RR variability, with a clinically sufficient prediction accuracy. RR variability can serve as an objective, continuously available, and non-invasive measurement to monitor midazolam-induced sedation in intubated and mechanically ventilated patients.

Adult↗
PubMed1996

The majority of autologous cytolytic T-lymphocyte clones derived from peripheral blood lymphocytes of a melanoma patient recognize an antigenic peptide derived from gene Pmel17/gp100.

Anti-melanoma cytolytic T-lymphocyte (CTL) clones were derived from peripheral blood lymphocytes of HLA-A2 melanoma patient LB265 after stimulation with the autologous tumor cell line LB265-MEL, which showed high expression of melanocyte-lineage specific genes. Of 55 CTL clones, 46 recognized HLA-A2-restricted antigens. These 46 CTL clones were studied for their ability to specifically release tumor necrosis factor in the presence of COS cells cotransfected with the HLA-A2 gene and the cDNA of either tyrosinase, Melan-A/MART1, Pmel17/gpl00, gp75/TRP1, or MSH receptor. Six CTL clones recognized the Melan-A/MART1 antigen, whereas the remaining 40 CTL clones recognized a Pmel17/gp100 antigen. These 40 anti-PmelI7/gpl00 CTL clones were all able to lyse T2 cells pulsed with the antigenic peptide YLEPGPVTA, as previously reported. The T-cell receptor beta chain hypervariable region was sequenced and found to be identical in the 15 CTL clones analyzed. Taken together, these data show a high frequency of Pmell7/gp100-specific T cells in autologous antitumor CTL clones derived from peripheral blood of a melanoma patient.

Amino Acid Sequence↗
PubMed1995

A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma.

We have identified an antigen recognized on a human melanoma by autologous cytolytic T lymphocytes. It is encoded by a gene that is expressed in many normal tissues. Remarkably, the sequence coding for the antigenic peptide is located across an exon-intron junction. A point mutation is present in the intron that generates an amino acid change that is essential for the recognition of the peptide by the anti-tumor cytotoxic T lymphocytes. This observation suggests that the T-cell-mediated surveillance of the integrity of the genome may extend to some intronic regions.

Alleles↗
PubMed1995

Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection.

We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33-MEL.A was obtained after surgery in 1988. A large number of CTL clones directed against LB33-MEL.A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that at least five different antigens were recognized on LB33-MEL.A by autologous CTL. Four of these antigens were found to be presented by HLA-A28, B13, B44 and Cw6, respectively. The patient remained disease-free until 1993 when a metastasis was detected and was used to obtain cell line LB33-MEL.B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33-MEL.A cells and showed no expression of HLA class I molecules except for HLA-A24. Using LB33-MEL.B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA-A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti-tumor CTL response.

Adult↗
PubMed1993

Human T cell lines and clones respond to IL-9.

The activity of IL-9 on human T cells was investigated. Human T cell lines and clones, derived from PBMC by stimulation with PHA, IL-2, and irradiated allogeneic PBMC, were found to express a strong IL-9R message at the RNA level and to proliferate in the presence of IL-9, irrespectively of their CD4+ or CD8+ phenotype. Moreover, tumor-specific CTL clones also responded to IL-9. Contrasting with other T cell growth factors, such as IL-2, IL-4, or IL-7, IL-9 did not induce the proliferation of freshly isolated T cells. However, a significant proliferative response to IL-9 could be observed after a 10-day activation of PBMC with PHA, IL-2, and feeders. Taken together, our results indicate 1) that the activity of IL-9 on human T cells is wider than initially anticipated on the basis of the data obtained so far with murine cells; and 2) that proliferative responses to IL-9 require previous activation.

Cell Line↗
PubMed1993

Genes coding for tumor antigens recognized by human cytolytic T lymphocytes.

In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by transfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone. The gene that transferred the expression of the antigen was named MAGE-1. It is a new gene, silent in normal tissues with the exception of testis, but expressed in several types of tumors. The antigen recognized by the CTL clone is a nonapeptide derived from the protein encoded by gene MAGE-1, and presented by the HLA class I molecule HLA-A1. Using two other antimelanoma CTL clones, we identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on this type of tumors. The identification of these tumor rejection antigens open new possibilities for the specific immunotherapy of cancer.

Antigen-Antibody Reactions↗
PubMed1992

Iron deficiency anemia in 1-year-old children of disadvantaged families in Montreal.

OBJECTIVES: To determine the prevalence of iron deficiency anemia among 1-year-old infants of disadvantaged families in Montreal as well as certain predictors of this condition. DESIGN: Cohort study. SETTING: Five poorest health districts in Montreal. PARTICIPANTS: Infants 10 to 14 months of age were identified from registration lists of births from May 1988 to August 1989. Those whose mother had less than 11 years of schooling and a family income below the government-defined low-income cutoff point were eligible. INTERVENTION: During a home visit capillary blood samples were obtained from the child, and the mother answered a questionnaire about infant-feeding practices. Infants with a serum ferritin level of 10 micrograms/L or less and either a hemoglobin level of 115 g/L or less or a mean corpuscular volume of 72 fL or less were considered as having iron deficiency anemia. RESULTS: Of the 299 mothers who were eligible and could be located 220 (74%) agreed to participate; 218 blood samples were available. Iron deficiency anemia was found in 25% of the infants (95% confidence interval [CI] 19% to 31%). The mean hemoglobin level was 115 (standard deviation 11) g/L. The serum ferritin level, assessed routinely in the last 62 infants, was 10 micrograms/L or less in 37% of the infants. The factors that were found to be predictors of iron deficiency anemia included the use of whole cow's milk before 6 months of age (odds ratio [OR] 3.56 [95% CI 1.07 to 11.26]) and the use of iron-fortified infant cereal for less than 6 months (OR 3.15 [95% CI 1.25 to 7.96]). A low birth weight and the use of iron-fortified formula for less than 6 months were associated with iron deficiency anemia. CONCLUSIONS: Despite a decrease in the prevalence of iron deficiency anemia among children of disadvantaged families in the United States socioeconomically disadvantaged infants in Montreal are at risk. Preventive measures must be taken to ensure adequate iron status in the first year of life.

Anemia, Hypochromic↗
PubMed1992

Precursor frequency analysis of human cytolytic T lymphocytes directed against autologous melanoma cells.

Limiting numbers of peripheral-blood mononuclear cells (PBMC) from melanoma patients were stimulated with irradiated autologous tumor cells in the presence of interleukins-2 and -4 and in the absence of feeder cells. The responder cells were restimulated every week. After 2 to 4 weeks, the microcultures were tested for their lytic activity against the autologous tumor cells. Significant lysis of the tumor cells was observed with a fraction of these microcultures, whereas no lysis was observed with control microcultures seeded without stimulator melanoma cells. Because our aim was to measure the precursor frequency of CTL showing specificity for the tumor, and not that of NK-like effectors that were also capable of lysing the melanoma cells, we used cold-target inhibition with an excess of NK target K562 to inhibit the NK-like activity. Microcultures whose lysis on the tumor cells was not abolished by K562 competition were observed. The specificity of these CTL clones was confirmed by the absence of lytic activity on autologous T-cell blasts. The numbers of microcultures with anti-tumor CTL activity fitted the zero-order of the Poisson distribution equation, indicating that they resulted from the activity of single T-cell clones. The frequency of anti-tumor CTL precursor cells (CTL-P) of 7 melanoma patients ranged from 1/900 to 1/33,000. Frequencies of anti-tumoral CTL-P were higher and NK-like effectors were less frequent when sorted CD8+ T lymphocytes were used as responder cells.

CD4-CD8 Ratio↗
PubMed1991

[Ovarian pregnancy after gamete transfer (gift). A case report].

A case of ovarian pregnancy after gamete transfer (GIFT) is reported in a 33-year old women who, after intensive stimulation therapy, experienced a right tubal pregnancy in one cycle and an ovarian pregnancy on the left side in the next. The incidence of ovarian pregnancies seems to have been increasing during the past years, comprising 3.3% of all extrauterine pregnancies. This may be influenced by the possibilities of sterility therapy today. Clinical presentation, possible pathogenesis, diagnostic steps and preferred management are described. The use of transvaginal sonography has improved the diagnosis of ectopic pregnancies and should be routinely used leading to an early diagnosis and organ-preserving therapy. This case report is intended to assist and promote the sensitivity towards an early diagnosis of this rare form of ectopic pregnancy.

Adult↗
PubMed1988

Ovarian stimulation for in-vitro fertilization: clomiphene and HMG.

Details of the problems and successes obtained after various forms of hormonal stimulation in an IVF programme are presented. The endocrine conditions normally existing in the natural menstrual cycle are discussed first, followed by analyses of the types of responses to clomiphene, clomiphene and HMG, HMG alone and LHRH agonists. Clomiphene produces fewer embryos than other treatments but gives a good control of follicle growth and ovulation. Clomiphene and HMG increases the number of available oocytes, and this raises the chance of pregnancy, but there is a greater heterogeneity in the follicular population. HMG alone is suitable for most conditions except for those with PCO syndrome and gives an average of six oocytes per treatment cycle. The problems associated with premature rises in levels of LH are overcome by using LHRH agonists with HMG, and this results in satisfactory numbers of oocytes but requires endocrine support in the luteal phase. The need for luteal phase support after various therapies remains unclear, and a calculation of the ratios between various steroids may help to clarify the need for it.

Clomiphene↗
PubMed1985

Polyspermy in in vitro fertilization of human oocytes: frequency and possible causes.

In an IVF program a total of 585 oocytes (180 patients) were examined for the presence of pronuclei 16 to 20 hours after the addition of spermatozoa. The overall fertilization rate was 71%, and in 58 (10%) of the fertilized oocytes, three or more pronuclei, indicating a failure of the block to polyspermy, could be observed. The frequency of polyspermy was related to the maturity of the oocyte, determined according to morphologic criteria. Immature oocytes showed a higher percentage of polyspermic fertilization (32%) compared to that of mature oocytes (6%). Preincubation of oocytes (for 0.5-1.5, 2-4, and 5-8 hours) prior to the addition of spermatozoa increased the fertilization rate (to 67%, 70%, and 83%, respectively). The polyspermy rate, however, was not significantly different between the various preincubation intervals (13%, 14%, and 19%, respectively). The polyspermy rate was affected by the number of spermatozoa used for in vitro fertilization. Insemination with 0.5-0.8, 1.0, or 1.5-2.0 X 10(6) spermatozoa/oocyte resulted in a polyspermy rate of 6%, 20%, and 32%, respectively. The appearance of polyspermic fertilization was not related to the age of the patient (which ranged from 20 to 45 years) nor to the method of ovarian stimulation (clomiphene, hMG, or clomiphene/hMG). Because of the high incidence of polyspermy under in vitro conditions it seems to be important to routinely examine the oocytes in the pronuclear stage. Reduction of the number of spermatozoa used for in vitro fertilization and the exact timing of insemination according to the maturity of the oocyte might reduce the occurrence of polyspermic fertilization.

Female↗