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R Levy

Publications and source records attributed to R Levy.

At least 433 records · Page 24Linked to original sources
PubMed1991

Transfer of specific immunity to B-cell lymphoma with syngeneic bone marrow in mice: a strategy for using autologous marrow as an anti-tumor therapy.

Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphomas. We used the 38C13 murine B-cell lymphoma model to explore the approach of transferring tumor antigen-specific immunity with syngeneic BM as a protective element. Mice serving as syngeneic marrow donors were twice immunized with tumor-derived surface Ig protein, the idiotype of which serves as a tumor-specific antigen, or with a control Ig of matched isotype. Naive lethally irradiated recipients reconstituted with marrow from immune donors showed serologic tumor idiotype-specific immunity, as well as protection against lethal tumor challenge. The immunoprotective effect of immune marrow was also shown in lethally irradiated recipients partially protected by specific immunization post-BMT. Combined donor and recipient immunization also replaced the requirement for the booster immunization of the donor. These results provide the rationale for active immunization with purified surface Ig from autologous tumor as an adjunct to autologous BMT in humans.

Animals↗
PubMed1991

Effect of 1,25-dihydroxyvitamin D3, lipopolysaccharide, or lipoteichoic acid on the expression of NADPH oxidase components in cultured human monocytes.

Human blood monocytes in culture gradually lose their capability to produce superoxide when stimulated. Addition of 10(-8) M 1,25-dihydroxyvitamin D3 [1, 25(OH)2D3], 2.5 ng/ml LPS, or 25 ng/ml lipotechoic acid (LTA) prevented this decrease in monocyte respiratory burst when added at initiation of culture. Monocytes cultured for 4 days in the presence of 1,25 (OH)2D3, LPS, or LTA retained the ability to produce superoxide and 1,25 (OH)2D3 actually increased the oxidative capacity compared with fresh monocytes. Furthermore, addition of 1,25(OH)2D3, LPS, or LTA to monocytes at day 4 of culture restored the oxidase activity by day 7 to the levels seen with fresh monocytes. Cytosol or membrane fractions from monocytes cultured with or without the agents indicated above were tested in a cell-free assay of superoxide production by mixing with fresh monocyte membrane or cytosol fractions, respectively. Membrane oxidase activity from these cultured monocytes showed only minimal changes regardless of the agent present or absent from the culture. However, the activity of cytosol fractions from these same cultured monocytes showed substantial differences depending upon the culture conditions and these changes correlated closely with changes in activity of the intact monocytes from which the cytosols were derived. Immunoblot analysis of monocyte membranes and cytosol was used to assess the amount of the 91-kDa and 22-kDa subunits of membrane oxidase cytochrome 558 (gp91 and p22), and the 47-kDa and 67-kDa cytosol oxidase factors (p47 and p67) in the different culture conditions. The gp91 and p22 decreased during culture of monocytes, although the decrease was only apparent by 7 days in culture. When 1,25 (OH)2D3, LPS, or LTA were present at the initiation of culture, then an increase in gp91 and p22 was seen as compared with fresh monocytes at day 4. When these agents were added at day 4 of culture, the levels of gp91 and p22 at day 7 were similar to fresh monocytes. The p67 cytosol oxidase component showed little change in amount by immunoblot regardless of the time in culture or whether 1,25(OH)2D3, LPS, or LTA were present. In contrast, the p47 cytosol oxidase factor decreased by day 4 of culture and was markedly depressed by day 7. Monocytes cultured in the presence of either 1,25(OH)2D3, LPS, or LTA preserved the expression of p47, whereas addition of these agents to monocytes at day 4 of culture restored the expression of p47 by day 7 to the level of fresh monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcitriol↗
PubMed1991

[Small cell lung cancers: intensive and short chemotherapy followed by irradiation. Results of a pilot study].

Twenty-six patients with localized small cell lung cancer received 3 monthly courses of intensive chemotherapy consisting of cisplatin (40 mg/m2/day on days 1, 2, 3), cyclophosphamide (750 mg/m2/day on days 4 and 5), adriamycin (50 mg/m2/day on day 5), vindesine (2 mg/m2/day on days 1 and 5), etoposide (100 mg/m2/day on days 1, 2, 3) and methylprednisolone (120 mg/m2/day on days 1 to 5). The first 10 patients received radiotherapy of the chest (3 Gy/day on days 7 and 8) and brain (2 Gy/day on days 7 and 8) after each course of chemotherapy, followed by complementary chest (27 Gy) and brain (22 Gy) radiotherapy after the end of the aplasia induced by the 3rd course of chemo-radiotherapy (alternate protocol: AP). In view of the toxicity of this protocol (4 deaths) and of the occurrence of 2 epidural relapses, the remaining 16 patients received the same 3 courses of chemotherapy followed by radiotherapy of the chest (55 Gy), brain (34 Gy) and spinal cord (34 Gy) (sequential protocol: SP). Haematological toxicity was controlled without problem in a medical oncology intensive care unit. The complete response rate (AP + SP) was 100 percent. The median survival rate was 26 months. Survival at 2 years was 20 percent with AP and 78 percent with SP (P = 0.002), this difference being due to the absence of iatrogenic deaths and epidural relapses. Intensive chemotherapy combined with radiotherapy deserves to be developed in the management of localized small cell lung cancer.

Actuarial Analysis↗
PubMed1991

Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis.

The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma.

Chromosome Mapping↗
PubMed1991

Ig VH gene expression among human follicular lymphomas.

Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire.

Base Sequence↗
PubMed1991

Ventricular enlargement and caudate hyperdensity in elderly depressives.

Twenty-five elderly patients (mean age 73 years, range 61-88 years) with major depression underwent cranial computed tomography (CT). The findings were compared with healthy age- and sex-matched controls. The radiodensity of the left and right heads of the caudate was significantly higher in the depressed patients (p less than 0.05). The third ventricle was significantly enlarged (p less than 0.05); this effect did not reach statistical significance for the lateral ventricles. Ventricle size in the patient sample increased with age, duration of illness, and number of depressive episodes. This effect was largely age-driven for the third ventricle. Enlargement of the anterior horns appeared to be primarily influenced by the combined effects of early onset and bipolarity of illness. Densitometric measurements of the grey and white matter did not show significant correlations with age, number, or frequency of depressive episodes, age of onset, or duration of illness.

Aged↗
PubMed1991

Autoantibody activity of immunoglobulins isolated from B-cell follicular lymphomas.

Previous work with monoclonal Igs (MIgs) has demonstrated that a high proportion of paraproteins bind to self-antigens such as the Fc fragment of IgG, Ii blood group antigens, cytoskeleton proteins, DNA, and myelin-associated glycoprotein (MAG). Recent work in CLL indicates that CD5+ B lymphocytes are frequently committed to production of autoantibodies. We have examined the antibody specificity of MIgs derived from the tumor cells of 31 different patients with CD5- B-cell lymphomas. Our results indicate that the tumor cells from 8 of these 31 patients (25.8%) express Igs with autoantibody activity. In two cases antibody activity was multispecific. In four cases, antibody activity was exclusively directed against the Fc fragment of IgG, whereas the two other cases bound to both Fc fragment of IgG and nuclear antigens. Most non-Hodgkin's lymphomas (NHL) are derived from CD5- B cells. These results indicate that like CLL, NHL also express Igs that frequently have autoantibody activity.

Antibodies, Monoclonal↗
PubMed1991

Tacrine in Alzheimer's disease.

The efficacy and safety of tacrine (tetrahydroaminoacridine) plus lecithin were studied in a randomised, double-blind, placebo-controlled, crossover study. Patients with probable Alzheimer's disease were selected from those attending the memory clinic at a psychiatric hospital. Of the 89 patients included, 24 were withdrawn, 19 because of side-effects, 4 with other illnesses, and 1 for non-compliance. The active treatment was the maximum tolerated dose of tacrine up to 150 mg daily plus 10.8 g lecithin daily. Patients were randomly assigned to active or placebo treatment and crossed over after 13 weeks' treatment and 4 weeks' washout to the other treatment. The main outcome measures were the mini mental state examination (MMSE), the abbreviated mental test score (AMTS), and the carer's rating of the activities of daily living scale. Analysis for the 65 patients who completed the trial showed a significant beneficial effect of tacrine over placebo in the MMSE score (p less than 0.0001; 95% confidence interval for group change on tacrine over that on placebo 1.67-3.71); 29 (45%) patients showed an improvement of 3 or more points on tacrine compared with 7 (11%) during placebo. The findings with the AMTS were similar (p = 0.0001; 95% CI 0.36-1.38) but the ADL score showed no significant treatment effect. There was substantial variation in response among the subjects. Dose-dependent rises in serum liver enzymes were common but reversible. Tacrine produced an improvement in key outcome measures roughly equivalent to the deterioration which might have occurred over 6-12 months. The clinical relevance of the findings is a matter for individual judgment.

Activities of Daily Living↗
PubMed1991

Computed tomography in Alzheimer's disease: a longitudinal study.

Sixty-three patients satisfying NINCDS/ADRDA criteria for Alzheimer's disease (AD) received neuropsychological tests and computed tomography (CT) scans 12 months apart. Significant deterioration occurred in all the cognitive tests and in the CT measures used, that is, lateral ventricular size, third ventricular size, and cortical atrophy. There was a wide variation in the size of the changes taking place; 14 of 63 patients showed no significant change and 6 showed a marked increase in ventricular size. However, neither group differed from the others in any demographic, cognitive, or other CT variables which suggested, on the CT measures used, that no clearly identifiable subgroups of AD were present. Change in CT indices was not related to initial severity of disease. An increase in ventricular size was related to deterioration of cognitive function. These results require further replication. The methodological drawbacks of such studies are discussed.

Aged↗
PubMed1991

An epitope on the transferrin receptor preferentially exposed during tumor progression in human lymphoma is close to the ligand binding site.

We have previously reported an anti-transferrin receptor antibody, Trump, which was originally selected for its ability to discriminate low- and high-grade lymphomas. This feature was distinct from the other anti-transferrin receptor antibodies such as OKT9. In the present study, further immunochemical analysis was performed to define the nature of the antigenic site recognized by the Trump antibody. Trump was found to block the binding of transferrin both to solubilized and to surface transferrin receptors; conversely, transferrin could block the binding of Trump only to surface transferrin receptors. Therefore, the epitope recognized by Trump is near but not identical to the transferrin binding site. Stimulation of peripheral blood lymphocytes with phytohemagglutinin induced both the OKT9 epitope and the Trump epitope, but 12-phorbol 13 myristate acetate induced only the OKT9 epitope. Growth of some cell lines was inhibited by Trump but not by OKT9. No structural difference was found between transferrin receptor molecules reactive with Trump and those reactive with OKT9. In support of these results, Trump was able to immunoprecipitate transferrin receptor molecules solubilized from low-grade follicular lymphoma cells even though it did not bind to the receptors exposed on the surface of these cells. These findings imply that low-grade lymphoma cells differ from high-grade lymphoma cells not in the structures of their transferrin receptors but in their exposure of the molecule on the cell surface.

Antibodies, Monoclonal↗
PubMed1991

Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell.

To investigate the clonal relationship between follicular lymphoma (FL) and transformed diffuse lymphoma (tDL), we examined the expression of tumor idiotype, immunoglobulin (Ig) gene rearrangements and sequence of Ig variable genes in paired tissue specimens. All 16 cases analyzed expressed surface immunoglobulin (sIg) on both the FL and the tDL, though the immunophenotype of one case of FL could not be definitively determined. In 14 of 15 cases, the surface immunophenotype was preserved; the exception was likely secondary to a class switch from IgM to IgG. In 12 of 13 cases, antiidiotypic monoclonal antibodies prepared against the FL reacted with the paired tDL. Analysis of Ig gene rearrangements in four cases by Southern blot hybridization showed evidence of clonal relationships in all cases though concordance was not seen with all probes tested (C kappa, C lambda, JH, PFL1, and PFL2). In the one case that had a discordant L chain rearrangement, sequence analysis of the L chain demonstrated a common mature B cell origin for both the FL and tDL. To determine whether tDL arose from one or more FL cells, the sequences of the H chain variable genes were analyzed. Individual clones of the V region gene of the FL showed a random distribution of changes throughout the sequence. In contrast, individual clones of the V region gene from tDL shared numerous nonrandom sequence alterations, implying a common single cell origin. In conclusion, tDL is a mature B cell and arises by transformation of a single FL cell.

Antibodies, Anti-Idiotypic↗
PubMed1991

Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.

Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

Adult↗