On certain peculiar diseases of old age.
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Geriatrics↗
Biomedical subjects
R Levy
Publications and source records attributed to R Levy.
Computerised tomography in Alzheimer's disease. Methods of scan analysis, comparison with normal controls, and clinical/radiological associations.
One hundred and thirty-eight patients satisfying NINCDS/ADRDA criteria for Alzheimer's disease (AD) and 36 normal controls underwent cranial CT. A comparison of methods of scan analysis showed good agreement between computer-assisted methods and visual ratings and planimetry. The CT scans of controls differed significantly from patients and a discriminant analysis, based on all CT measures, predicted group membership (control or patient) in 81% of cases. Within the AD group, cortical atrophy correlated with age and duration of illness. Global tests of cognitive function correlated significantly with both cortical atrophy and ventricular size. Subjects who died in a three-year follow-up had more atrophy and larger third ventricles than survivors, but this effect was due entirely to increased age.
Aged↗
Radiolabeled antibodies: another form of cytotoxic treatment.
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Antibodies↗
Idiotype vaccination post-bone marrow transplantation for B-cell lymphoma: initial studies in a murine model.
Studies in the 38C13 model, a lethal murine B-cell lymphoma of C3H origin, have previously demonstrated the efficacy of immunization with tumor idiotype against established tumors, especially in the setting of reduced tumor burden when combined with chemotherapy. We have extended these studies to test the protective effect of immunization with 38C13 idiotype protein (38C-Id), coupled to KLH and administered with an adjuvant, against a subsequent tumor challenge following lethal total body irradiation (950 R) and reconstitution with syngeneic bone marrow (20 x 10(6) cells) from normal donors. Animals prepared in this manner which were immunized with 38C-Id after 3 weeks recuperation and challenged with 1000 38C13 tumor cells 2 weeks later demonstrated significantly longer survival when compared to control animals which had been immunized with irrelevant idiotype protein. Irradiated reconstituted mice immunized after 5 weeks recuperation and challenged with 1000 tumor cells also demonstrated prolonged survival compared to controls, as well as a small number of cures (approximately 40%). Anti-38C-Id antibodies, implicated in the mechanism of idiotype induced anti-tumor immunity in this model, were detectable after immunization at both 3 and 5 weeks, although there was no significant correlation between serum antibody levels and survival of individual mice. These results suggest that immunologic recovery as early as 3 to 5 weeks following marrow grafting is sufficient to allow induction of idiotype-specific, anti-tumor immunity and form a model for our clinical trial of tumor idiotype vaccination for patients with B-cell lymphoma undergoing autologous BMT.
Animals↗
[Paraphrenia in the elderly. Psychopathologic and computer tomography indications of two subtypes].
Psychopathological and cranial computed tomography findings in 48 patients with late paraphrenia were compared with the findings in 40 normal controls. 19 patients with late paraphrenia and first rank symptoms showed significantly less cortical atrophy than 29 patients without first rank symptoms (p less than 0.01). There were no significant differences of ventricular enlargement, cerebellar atrophy, the presence of leukoaraiosis or basal ganglia mineralisation between the late paraphrenic and control groups. In contrast to the controls, cortical atrophy, ventricular enlargement and the presence of leukoaraiosis were not age-related. These results may indicate different origins of late paraphrenia with or without first rank symptoms.
Aged↗
Squamous cell carcinoma of the oral tongue.
Between 1958 and 1983 at Beilinson Medical Center, Petah Tiqva, Israel, 75 patients were diagnosed as having squamous cell carcinoma of the body of the tongue. Of these, 42 were male and 33 female and the average age at the time of diagnosis was 61.6 years. 29.33% were in clinical stage I, 36% in stage II, 26.67% in stage III and 8% in stage IV. Fifteen patients underwent only surgery, nine received only irradiation and 51 received combined treatment. The 5-year survival rate was 68.3% with a significant difference between that for stage I (90%) and stage II (83.7%) and that for stages III and IV (43.07% and 0%, respectively) (P less than 0.001). Among the 24 with recurrence of the malignancy, 20 died despite treatment and four patients died of causes unrelated to the malignancy. From this experience it was concluded that local excision of the tumor should be performed only in stage I patients and that in stage II patients prophylactic treatment of the neck (neck dissection and irradiation) should be undertaken because of the high incidence of occult metastases.
Adult↗
Neuroanatomical correlates of clinical misidentification and misperception in senile dementia of the Alzheimer type.
BACKGROUND: Impaired frontal lobe and/or nondominant hemisphere lesions have been described in patients with typical misidentification syndromes (e.g., Capgras' syndrome or reduplicative paramnesia) who had various underlying psychiatric or neurologic disorders. In a prospective long-term study, the authors examined computed tomography measurements of patients with senile dementia of the Alzheimer type (DAT) to determine whether the forms of misidentification they suffered might correlate with organic factors. METHOD: One hundred twenty-eight consecutive DAT patients were examined by means of standardized clinical instruments (Mini-Mental State score, CAMCOG, the Benton facial recognition test, the Kendrick object learning test, CAMDEX, and the Geriatric Mental State Schedule) and computed tomography. RESULTS: Of the 128 patients, 40 showed symptoms of misidentification; 25 of them misidentified other people in their homes, 7 misidentified their own mirror images, and 7 misidentified television images as being real. Computer-assisted planimetric computed tomography measurements showed that patients with misidentification syndromes had significantly larger right anterior horn areas of the lateral ventricle and significantly larger left anterior brain areas than did patients without such symptoms. CONCLUSIONS: The authors conclude that an accentuated degeneration of the right frontal lobe (and a relative preservation of the left frontal lobe) may be associated with delusional misidentification symptoms in DAT.
Aged↗
Influence of calcium channel blockers on polymorphonuclear and monocyte bactericidal and fungicidal activity.
The effect of calcium channel blocking agents on the killing activity of human peritoneal polymorphonuclears (PMN) and monocytes was studied. The organisms used were Escherichia coli, Staphylococcus aureus and Candida albicans. The pharmacological concentration of verapamil (5 microM), nifedipine (10 microM) and diltiazem (10 microM) caused a similar inhibition of killing activity in both PMN and monocytes. The calcium channel blockers significantly reduced the in vitro killing of E. coli, S. aureus and C. albicans by PMN to about 47%, 30% and 20% respectively, compared with 81 +/- 6%, 65 +/- 5% and 40 +/- 4% in the controls. The killing of these organisms by monocytes was 60 +/- 6%, 42 +/- 7% and 35 +/- 5% respectively, as compared with 30%, 20% and 17% in the presence of these drugs. The bactericidal activity of the phagocytic cells from patients under treatment with calcium channel blockers was not affected and was found to be within the normal range, indicating that calcium channel blockers do not cause an irreversible impairment in PMN and monocyte killing activity. However, their potential inhibition of phagocytic cell activity should be taken into consideration during treatment.
Adult↗
[Rhomboencephalitis caused by Listeria monocytogenes: a case studies with magnetic nuclear resonance].
Central nervous system infections due to Listeria monocytogenes result in a variety of clinical syndromes ranging from meningitis to rhomboencephalitis. We report the case of a previously healthy patient with rhomboencephalitis in whom the CT scan was normal, while magnetic resonance imaging (MRI) confirmed the diagnosis. We review the literature and emphasize the value of MRI for timely diagnosis.
Encephalitis↗
[Brain metastasis from malignant melanoma during interleukin-2 therapy].
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Brain Neoplasms↗
Combined syngeneic bone marrow transplantation and immunotherapy of a murine B-cell lymphoma: active immunization with tumor-derived idiotypic immunoglobulin.
Recurrence of the underlying malignancy remains a major cause of treatment failure after autologous bone marrow transplantation (BMT) for patients with lymphoma. In this regard, we have developed an immunotherapeutic approach designed to induce resistance against residual tumor cells persisting after BMT. Previous studies in the model system of 38C13, a lethal B-cell lymphoma of C3H origin, have shown that active immunization with purified tumor-derived surface immunoglobulin (Id), as a tumor-associated antigen, produces resistance to tumor growth. Id immunization of lethally irradiated mice at 3 or 5 weeks after reconstitution with syngeneic bone marrow resulted in significantly prolonged survival after tumor challenge compared with nonspecifically immunized controls. Low levels of idiotype-specific antibody were also demonstrated in the sera of specifically immunized mice at this early time, when other functional studies in the literature of immunocompetence after syngeneic reconstitution might have predicted incomplete recovery. Immunization of mice before lethal irradiation and syngeneic marrow reconstitution also induced significant resistance to tumor challenge, suggesting the persistence of established host antitumor immunity through total body irradiation. These studies demonstrate the feasibility of id immunization in conjunction with bone marrow transplantation.
Animals↗
Accuracy of clinical diagnosis of Alzheimer's disease.
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Aged↗
Induction of the respiratory burst in HL-60 cells. Correlation of function and protein expression.
Differentiation of myeloid cells is associated with the gradual acquisition of functional capacity to produce a respiratory burst. In our study HL-60 cells were differentiated to the monocyte phenotype with IFN-gamma or 1,25-dihydroxyvitamin D3, or to the neutrophil phenotype with retinoic acid or DMSO to compare the time-course of expression of membrane and cytosolic oxidase components, and to correlate this with the appearance of a functional oxidase. Over a 6-day period of induction the rank order of the ability of these agents to induce expression of PMA-stimulated superoxide production was: IFN-gamma greater than 1,25(OH)2D3 greater than retinoic acid greater than DMSO. Immunoblot analysis of HL-60 membranes and cytosol was used to assess the amount of specific phagocyte oxidase factors (91 and 22 kDa subunits of membrane cytochrome b558 (gp91 and p22), and 47 and 67 kDa cytosol oxidase factors (p47 and p67)). HL-60 cell membranes or cytosol were tested in a cell-free assay of superoxide production by mixing with normal neutrophil cytosol or membranes, respectively. p47 was first detected at 16 h of differentiation, increasing similarly thereafter with all induction regimens and reaching a maximum by 3 to 4 days. The earliest detection of p67 varied from 2 to 6 days depending on the inducing agent and appeared to be the limiting cytosol component. Small amounts of both subunits of cytochrome b558 were detected in uninduced HL-60 membranes, but were sufficient to support substantial superoxide production when combined with normal neutrophil cytosol. Both cytochrome b558 subunit proteins and membrane oxidase activity increased during differentiation in parallel. We conclude that membrane and cytosol components of the NADPH oxidase complex appear at different times and increase differently during HL-60 differentiation. The production of p67 is the major factor limiting the respiratory burst during HL-60 differentiation.
Blotting, Western↗
TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen.
A murine mAb, 5A6 (IgG1), has been isolated by immunization with a human B lymphoma cell line and screening for growth inhibition. The antibody immunoprecipitated a single chain protein of 26 kDa from cell lysates made with Triton X-100 but additional proteins were precipitated when cell lysates were made with the milder detergent CHAPS (3-[3-cholamidopropyl)dimethylammonio)-1-propane sulfate). We have identified one of these coprecipitated molecules as the 16-kDa Leu-13 Ag. 5A6 and anti-Leu-13 showed similar, although not identical, reactivity, growth inhibition and temperature-dependent aggregation effects among hematolymphoid cell lines. The aggregation induced by 5A6 and anti-Leu-13 was not dependent on LFA-1 (lymphocyte function-associated Ag-1). The cell-surface expression of both TAPA-1 (target of an antiproliferative antibody-1) and Leu-13 could be down-modulated by binding to their respective antibodies and they could be reciprocally comodulated. These results suggest that TAPA-1 and Leu-13 form a complex on the cell surface and play a role in growth control through a common pathway.
Antibodies, Monoclonal↗
Gallium-transferrin binding in Alzheimer's disease.
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Aged↗
Production of myeloid cell cytosols functionally and immunochemically deficient in the 47 kDa or 67 kDa NADPH oxidase cytosolic factors.
Professional phagocytes contain a unique NADPH oxidase responsible for the production of microbicidal oxidants. Activation of this oxidase requires participation of cytosolic and membrane proteins, but the interactions of these components are incompletely understood. Patients with autosomal recessive Chronic Granulomatous Diseases (CGD) are characterized by functional defects in phagocyte oxidase activity resulting from a deficiency of either a 47 kDa (p47) or a 67 kDa (p67) cytosolic oxidase component. Cytosols from such patients are valuable for biochemical studies of the oxidase, but are not generally available because CGD is a rare disorder. The present study illustrates means of producing cytosols functionally and immunochemically deficient in either p47 or p67. Cytosol from monocytes cultured for 6 days is immunochemically deficient in p47 but not p67, while cytosol from HL-60 cells induced with retinoic acid for 3 days is deficient in p67 but not p47. Each of these cytosols fail to generate superoxide when added to neutrophil membranes in a cell-free assay but complement each other when combined. Complementation studies in which these cytosols were mixed in the cell-free assay with p47- or p67- deficient CGD cytosol established the functional characteristics of the experimentally produced cytosols.
Cell-Free System↗
Determinants of the antitumor effect of radiolabeled monoclonal antibodies.
The murine B-cell lymphoma 38C13 model was used to study the radiobiological effect of 131I-monoclonal antibody (MAB) therapy compared with dose equivalent external beam irradiation. Continuous exponentially decreasing low dose rate (LDR) gamma-irradiation, and multiply fractionated (MF) X-irradiation were compared with dose equivalent 131I-MAB. The relative therapeutic efficacy of radioimmunotherapy, and the relative contribution of (a) low dose rate; (b) whole body irradiation; and (c) microdosimetry to the overall effect were determined. Groups of mice with or without B-cell lymphoma were treated with either (a) 131I-anti-idiotype MAB; (b) 131I-isotype-matched irrelevant control MAB; (c) 5-15 Gy 250 kV X-irradiation given as a single fraction; (d) 2.5-30 Gy 250 kV X-irradiation given in 10 fractions/2 weeks; or by (e) continuous exponentially decreasing gamma-irradiation via a 137Cs source, which simulated the effective t1/2 of the 131I-MAB. In tumor-free mice the LD50/30 was approximately 10 Gy for MF and LDR external irradiation, and 11-12 Gy for 131I-MAB. However, the effect of these modes of irradiation on tumor size differed significantly. The cumulative percentage of tumor reduction averaged over 12 days was 0.635 +/- 0.055%/Gy for MF, and 1.36 +/- 0.061%/Gy for LDR external irradiation (a relative efficacy factor of 1.63 for LDR irradiation; P = 0.01). Assuming homogeneous body distribution, the tumor reduction effect over 12 days for 131I-MAB was 2.064 +/- 0.133%/Gy for specific, and 1.742 +/- 0.1%/Gy for nonspecific isotype-matched irrelevant 131I-MAB (P = 0.02). When 131I-MAB was compared to LDR external irradiation, the relative efficacy factor was 1.99 (P less than 0.001). In summary, there was a dose rate effect on tumor response, which may in part explain the efficacy of radioimmunotherapy. The additional effect of 131I-MAB on tumor response was only partially explained by the cumulative concentration ratio of 131I-MAB tumor/131I-MAB whole body, which was on average 1.7. This relatively low concentration ratio was partly due to tumor-mediated dehalogenation. Thus, the overall tumor response was a function of the total dose, dose rate, and both the specific and nonspecific distribution of 131I-MAB.
Animals↗
Idiotype vaccination against murine B cell lymphoma. Humoral and cellular requirements for the full expression of antitumor immunity.
The roles of humoral and cellular antitumor immune responses induced by immunization with tumor-derived idiotypic IgM were studied in a syngeneic, transplantable B cell lymphoma (38C13) of C3H mice. Id vaccination with keyhole limpet hemocyanin-conjugated Id induced protection against a subsequent lethal tumor challenge. Such immunizations elicited anti-idiotypic antibodies that were cytotoxic in in vitro antibody-dependent cellular cytotoxicity assays as well as in vivo passive transfer experiments. L3T4+ T cells, which proliferated in vitro in response to the specific Id protein, were also induced. However, cells mediating direct cytotoxicity, either in vitro or in vivo, were not observed in the lymph nodes, spleens, or peritoneal cavity of immune mice or at the site of tumor regression as demonstrated by using a tumor sponge implantation model. In addition, in vitro sensitization of immune lymphocytes against 38C13 tumor cells failed to induce cytotoxicity. Immunization with lipid conjugated Id also elicited a T cell proliferative response but failed to induce anti-idiotypic antibodies and did not confer resistance to tumor growth. These results suggest that anti-idiotypic antibodies play the major role in the destruction of 38C13 tumor cells. However, in vivo depletion of L3T4+ or Lyt-2+ cells from 38C-Id-keyhole limpet hemocyanin-immunized mice resulted in diminished protection against a tumor challenge. Thus, although humoral responses appear to play the predominant part in tumor destruction, cellular responses are also required for the full expression of antitumor immunity in this system.
Animals↗