Strategy for genetic analysis in hereditary neuropathy.

Inherited neuropathies are a heterogeneous group of slowly progressive disorders affecting either motor, sensory, and/or autonomic nerves. Peripheral neuropathy may be the major component of a disease such as Charcot-Marie-Tooth disease or a feature of a more complex multisystemic disease involving the central nervous system and other organs. The goal of this review is to provide the clinical clues orientating the genetic diagnosis in a patient with inherited peripheral neuropathy. This review focuses on primary inherited neuropathies, amyloidosis, inherited metabolic diseases, while detailing clinical, neurophysiological and potential treatment of these diseases.

Comparison of Lewis-Sumner syndrome with chronic inflammatory demyelinating polyradiculoneuropathy patients in a tertiary care centre.

BACKGROUND AND PURPOSE: Whether the Lewis-Sumner syndrome (L-SS) is a distinct entity from other types of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP-ot) remains controversial. METHOD: The clinical/electrophysiological characteristics and long-term outcomes of 45 L-SS and 35 CIDP-ot patients were retrospectively compared. RESULTS: The CIDP-ot group was composed of 11 patients with a typical CIDP, 17 with a pure sensory form, four with a distal form and three with a pure motor form. In the L-SS group, asymmetric (P < 0.001) and monomelic involvement (P = 0.04) of the upper limbs (P < 0.001) was significantly more frequent; paucisymptomatic forms (Overall Neuropathy Limitations Scale ≤ 1) were less frequent (P < 0.001); electroneuromyography showed that conduction block in intermediate nerve segments was the main demyelinating feature, with frequent F-wave abnormalities on nerves without conduction block (44%). Long-term prognosis was globally poorer in the L-SS group with more frequent aggravation during treatment (P = 0.02), less frequent treatment withdrawal (P = 0.03) and longer time to achieve successful withdrawal (39 vs. 15 months). CONCLUSIONS: Our study suggests that L-SS patients have a less favourable therapeutic response rate and long-term outcomes. Rapid differentiation of L-SS from other forms of CIDP is important in order to anticipate a more complicated disease course management, with from one side the inefficacy or even harmfulness of corticosteroids and from the other side a difficult weaning procedure. A prospective study is necessary to confirm these results.

Botulinum toxin therapy improves masseter spasticity in Amyotrophic Lateral Sclerosis.

Fifteen ALS patients, with troublesome symptoms linked to masseter spasticity, benefited from BoNT-A injections in each masseter. Based on the medical records of patients, the effect of the first injection was assessed one month later. We retrospectively collected information for 12 patients. Eight of them reported a beneficial effect after the injection for the following symptoms: trismus, tongue, lip and cheek biting, and jaw clonus. Five patients indicated that dental care was easier after injection. Our study showed that injections of BoNT-A unequivocally reduced masseter spasticity in ALS patients who subsequently enjoyed greater comfort in their daily living.

New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study.

OBJECTIVES: Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA), a fatal progressive neurodegenerative disorder associated with autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the clinical spectrum of OH in a large European cohort of patients with MSA and (2) to investigate whether a prolonged postural challenge increases the sensitivity to detect OH in MSA. METHODS: Assessment of OH during a 10 min orthostatic test in 349 patients with MSA from seven centres of the European MSA-Study Group (age: 63.6 ± 8.8 years; disease duration: 4.2 ± 2.6 years). Assessment of a possible relationship between OH and MSA subtype (P with predominant parkinsonism or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS) scores and drug intake. RESULTS: 187 patients (54%) had moderate (> 20 mm Hg (systolic blood pressure (SBP)) and/or > 10 mm Hg (diastolic blood pressure (DBP)) or severe OH (> 30 mm Hg (SBP) and/or > 15 mm Hg (DBP)) within 3 min and 250 patients (72%) within 10 min. OH magnitude was significantly associated with disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and supine hypertension. OH severity was not associated with MSA subtype. Drug intake did not differ according to OH magnitude except for antihypertensive drugs being less frequently, and antihypotensive drugs more frequently, prescribed in severe OH. CONCLUSIONS: This is the largest study of OH in patients with MSA. Our data suggest that the sensitivity to pick up OH increases substantially by a prolonged 10 min orthostatic challenge. These results will help to improve OH management and the design of future clinical trials.

Validation of the French version of the MSA health-related Quality of Life scale (MSA-QoL).

INTRODUCTION: Multiple system atrophy (MSA) has considerable impact on health-related quality of life. The MSA health-related Quality of Life scale (MSA-QoL) is a patient-reported questionnaire, which has been recently designed to evaluate the quality of life in MSA. The objective of the present study was to validate the French version of the MSA-QoL questionnaire. METHODS: One hundred and thirty-six consecutive MSA patients were included in the study. Four patients with more than 10% missing responses were excluded from the final analysis. Data quality, scaling assumptions, acceptability, reliability and validity were assessed similar to the original validation of the English version. RESULTS: Missing responses were low, item and subscale scores were evenly distributed and floor and ceiling effects were negligible. Item-total correlations were higher than the recommended greater than 0.30 and internal consistency was high for all subscales. Test-retest reliability was good for all subscales. Validity was supported by moderate interscale correlations between the subscales and the predicted correlations with other scales assessing motor disability, activities of daily living, quality of life and mood. DISCUSSION: The French version of the MSA-QoL displays robust psychometric properties similar to the English version. CONCLUSION: The French version of MSA-QoL seems suitable for assessing quality of life in French speaking MSA patients.

[White matter lesions leading to the diagnosis of pseudoxanthoma elasticum]. / Hypersignaux de la substance blanche révélant un pseudoxanthome élastique.

Pseudoxanthoma elasticum (PXE) is an inherited connective tissue disease characterized by skin, eye, cardiovascular, and, less often, cerebrovascular manifestations. We report the case of a 32-year-old woman who presented with fortuitously discovered cerebral white matter lesions. The pattern of the lesions was compatible with vascular leucopathy. Neurological examination, CSF and biological assessment were normal. Physical examination demonstrated cutaneous lesions characterized by yellowish papules in the neck and axilla with calcification of elastic fibres showed on the skin biopsy and retinal angioid streaks, which made PXE a plausible diagnosis. Sequencing of the ABCC6 gene confirmed PXE. Thus, PXE must be considered when confronted with cerebral microangiopathy of undetermined origin.

Systemic gene expression after intravenous DNA delivery into adult mice.

Direct gene transfer into adult animals resulting in generalized or tissue-specific expression would facilitate rapid analysis of transgene effects and allow precise in vivo manipulation of biologic processes at the molecular level. A single intravenous injection of expression plasmid:cationic liposome complexes into adult mice efficiently transfected virtually all tissues. In addition to vascular endothelial cells, most of the extravascular parenchymal cells present in many tissues including the lung, spleen, lymph nodes, and bone marrow expressed the transgene without any apparent treatment-related toxicity. The transgene was still expressed in large numbers of cells in multiple tissues for at least 9 weeks after a single injection. Expression could be targeted to specific tissues and cell types, depending on the promoter element used.

Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery.

We have characterized the relationships between the design of cationic liposomes as a gene transfer vehicle, their resulting biodistribution and processing in animals, and the level and sites of gene expression they produce. By redesigning conventional cationic liposomes, incorporating cholesterol (chol) as the neutral lipid and preparing them as multilamellar vesicles (MLV), we increased the efficiency of cationic liposome:DNA complex (CLDC)-mediated gene delivery. Expression of the luciferase gene increased up to 1,740-fold and of the human granulocyte-colony stimulating factor (hG-CSF) gene up to 569-fold due to prolonged circulation time of injected CLDC, and increased uptake and retention in tissues. The level of gene expression per microgram of DNA taken up per tissue was 1,000-fold higher in lung than in liver, indicating that in addition to issues of delivery and retention of injected DNA, tissue-specific host factors also play a central role in determining the efficiency of expression. Vascular endothelial cells, monocytes, and macrophages are the cell types most commonly transfected by intravenous injection of CLDC.

Fetal gene transfer by transuterine injection of cationic liposome-DNA complexes.

In utero injection of cationic liposome-DNA complexes (CLDCs) containing chloramphenicol acetyltransferase, beta-galactosidase (beta-gal), or human granulocyte colony-stimulating factor (hG-CSF) expression plasmids produced high-level gene expression in fetal rats. Tissues adjacent to the injection site exhibited the highest levels of gene expression. Chloramphenicol acetyltransferase expression persisted for at least 14 days and was reexpressed following postnatal reinjection of CLDCs. Intraperitoneal administration of the hG-CSF gene produced high serum hG-CSF levels. X-gal staining demonstrated widespread beta-gal expression in multiple fetal tissues and cell types. No toxic or inflammatory responses were observed, nor was there evidence of fetal-maternal or maternal-fetal gene transfer, suggesting that CLDCs may provide a useful alternative to viral vectors for in utero gene transfer.

Liposome-based therapy of human ovarian cancer: parameters determining potency of negatively charged and antibody-targeted liposomes.

Liposomes containing cytotoxic agents may be highly efficacious for intracavitary therapy of malignancies such as ovarian carcinoma, which resides principally in the peritoneal cavity. We have examined in vitro the cytotoxicity of a variety of liposome-drug formulations against OVCAR-3, a human ovarian cancer cell line. Two drugs tested, methotrexate-gamma-aspartate and 5-fluoroorotate, show increased cytotoxicity on various cultured cell lines following encapsulation in liposomes and can be considered liposome-dependent agents. With the optimal lipid composition used in this study, the maximal increase in potency on OVCAR-3 is 2.6-fold for methotrexate-gamma-aspartate and 5.2-fold for 5-fluoroorotate. Studies on liposome-cell association suggest a low capacity of OVCAR-3 to bind and internalize phospholipid vesicles, which limits the in vitro potency of liposomes for these cells. OC-125, a monoclonal antibody recognizing an antigen common to a number of human ovarian cancers (CA-125), has been coupled covalently to the liposome surface. Liposomes bearing OC-125 and containing methotrexate-gamma-aspartate show an 8-fold increase in potency against OVCAR-3 cells in a 96-h growth inhibition assay. Briefer exposure of tumor cells to treatment accentuates the advantage of targeted liposomes. The cytostatic effect of 1 h exposure to OC-125 liposomes is 100-fold greater than the equivalent exposure to free drug and equal to the maximal cytostatic effect achieved with free drug for 96 h. Attachment of OC-125 antibody also confers upon liposomes the capacity to recognize OVCAR-3 cells growing as an ascites tumor in nude mice. After i.p. injection, control liposomes bind tumor cells in relatively low numbers, while fluorescent OC-125 liposomes can be observed bound specifically to tumor cell masses for periods of days.

Immunomodulatory and toxic effects of free and liposome-encapsulated tumor necrosis factor alpha in rats.

Tumor necrosis factor alpha has potent immunomodulatory and antitumor activity, but its therapeutic applications may be limited by its significant host toxicity. We showed that liposome-encapsulated recombinant human tumor necrosis factor alpha (rHuTNF-alpha) retained full anticellular activity in vitro. We then assessed the immunomodulatory and toxic effects of two different doses of i.v. free or liposome-encapsulated rHuTNF-alpha in normal rats. Both free and liposome-encapsulated rHuTNF-alpha significantly enhanced alveolar macrophage- and blood monocyte-mediated interleukin 1 release and tumor cell lysis, as well as natural killer cell cytotoxicity, when compared to buffer-treated controls. However, administration of rHuTNF-alpha in liposomes substantially reduced tumor necrosis factor alpha-mediated toxicity. Animals receiving liposome-encapsulated rHuTNF-alpha showed significantly less tissue injury, gastric retention, and circulating leukocyte shifts than animals receiving free rHuTNF-alpha. In addition, liposome-based delivery significantly increased lung and liver uptake of rHuTNF-alpha. Therefore, liposome-encapsulated rHuTNF-alpha retains immunomodulatory activity, significantly reduces toxic inflammatory effects, and may allow targeting of tumor necrosis factor alpha to selected organs after i.v. administration.

Targeting of anti-Thy 1.1 monoclonal antibody conjugated liposomes in Thy 1.1 mice after intravenous administration.

125I-labeled liposomes, conjugated to an anti-Thy 1.1 monoclonal antibody (MRCOX7), demonstrated up to 7.4-fold greater lymph node uptake than liposomes conjugated to non-specific monoclonal antibody (R-10) after intravenous injection into Thy 1.1 (AKR-J) mice. Uptake of anti-Thy 1.1-conjugated liposomes by the lymph nodes of AKR-J mice was 3-times greater than their uptake by lymph nodes of Thy 1.2 (AKR-Cu) mice. Lymph node localization of anti-Thy 1.1-liposomes was equal to that of control monoclonal antibody-liposomes in Thy 1.2 mice. Conjugation to either monoclonal antibody substantially increased liposome clearance by the liver, while decreasing liposome uptake in a number of organs outside the reticuloendothelial system. Changes in liposome size and phospholipid composition did not significantly alter these results. Administration of a large predose of unconjugated liposomes prior to injection of MRCOX7-conjugated liposomes increased blood levels and reduced liver uptake of the monoclonal antibody-liposome conjugates, but did not further enhance lymph node uptake. This study demonstrates that targeting of liposomes by conjugation to the appropriate monoclonal antibody, can significantly increase their uptake in lymph nodes which contain high levels of cells expressing the target antigen. However, conjugation to monoclonal antibody also increases clearance of liposomes by the liver. To increase the uptake of monoclonal antibody-conjugated liposomes in target tissue, substantial reduction of their clearance by the reticuloendothelial system will be required.

Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes.

Cationic liposomes mediate efficient transfection of mammalian cells, but the manner in which cells internalize and process cationic liposome-DNA complexes has not been well characterized. We exposed several cell types, including human and murine erythroleukemia cells. African green monkey kidney cells (CV-1), isolated rat alveolar type II cells and alveolar macrophages to DNA-cationic liposome complexes containing N-(1-2,3-dioleyloxypropyl)-N,N,N-triethylammonium (DOTMA) and Dioleylphosphatidylethanolamine (DOPE). The morphology of liposome-cell interactions was assessed by electron microscopy. Liposome preparations were complexed to colloidal gold particles or to both plasmid DNA and gold particles. Cells treated with DOTMA liposome-DNA complexes demonstrated endocytosis of the liposome-DNA complexes in coated pits, which were seen in early endosomes, late endosomes, and lysosomes. In isolated alveolar type II cells, the gold-labelled DOTMA lipid apparently mixed with the contents of lamellar bodies. In most cells, gold particles were dispersed throughout the cytoplasmic matrix. In a small proportion of CV-1 and U937 cells, a membrane system resembling the endoplasmic reticulum developed within the nucleus. This novel structure was also present in nuclei after they were isolated from CV-1 cells and then mixed with DOTMA-containing liposomes. Membranes which form after exposure to DOTMA-containing liposomes were 10 nm in thickness as compared to the approx. 8 nm thickness of endogenous cellular membranes. Based on these morphologic observations, we propose that the main route of entry of cationic liposomes into cells is by endocytosis. In some instances, the endosomal compartment releases its cationic liposome-DNA contents into the cytoplasmic matrix. Occasionally, liposomes may enter the nucleus by fusion with the nuclear envelope, creating vesicular and reticular intranuclear membranes. It is not clear at present which, if any of these morphological observations correlates with transfection mediated by cationic liposomes.

EEG in adults in the laboratory or at the patient's bedside.

Electroencephalogram (EEG) recording in the laboratory lasts at least 20 minutes and uses 19 active electrodes. It includes rest periods, stimulation procedures, a 3-mn hyperventilation period and intermittent photic stimulation (IPS). Recorded at the bedside, the EEG uses at least eight electrodes; the stimulation procedures, duration of the EEG and need to repeat the examination depend on the indication. Simultaneous video recording is recommended. The EEG report describes the basic rhythm, its reactivity and pathological activities, whether epileptic or not, and their organization. The synthetic conclusion interprets the results while taking into account the clinical context and contributes, if possible, diagnostic and/or therapeutic help in patient management. EEG performed as soon as possible after a seizure is essential for the diagnosis and initial management of epilepsy. It is helpful to characterize the epileptic syndrome in order to initiate optimal treatment. EEG is also useful in managing the withdrawal of antiepileptic drugs. EEG is also extremely useful in case of impaired consciousness, confusional state or even acute or subacute cognitive disorders. It is the only available tool able to validate the diagnosis of non-convulsive status epilepticus presenting with confusional state. EEG helps in the diagnosis of toxic or metabolic encephalopathy and can assess its severity, especially in hepatic encephalopathy. Except in rare exceptions, EEG is not routinely indicated for the evaluation of typical vasovagal syncope, headaches, dizziness, typical transient global amnesia and transient ischemic attack. EEG is irreplaceable in the diagnosis and management of certain severe and frequent pathologies involving the cerebral cortex.

Evaluation of the role of lipoprotein metabolism genes in systemic cationic liposome-mediated gene transfer in vivo.

Germ line gene disruption and gene insertion are often used to study the function of selected genes in vivo. We used selected knockout and transgenic mouse models to attempt to identify lipoprotein-related genes and gene products that regulate the process of intravenous cationic liposome-DNA complex (CLDC)-based gene delivery. Several observations suggested that proteins involved in lipoprotein metabolism might be important in influencing the delivery and/or expression of CLDC. First, in vitro transfection of either K562 or CHO cells by CLDCs was enhanced by the presence of a functional low-density lipoprotein receptor (LDLR). Second, pretreatment of mice with 4-aminopyrazolopyrimidine (4APP), an agent that alters lipoprotein profiles in mice, significantly decreased expression of luciferase (luc) after intravenous injection of CLDC-luc complexes in mice. Therefore, we tested mouse model systems either deficient for, or overexpressing, selected genes involved in lipoprotein metabolism, for their potential to regulate intravenous, CLDC-based gene delivery. Although homozygous knockout mutation in the apoE gene caused a significant decrease in gene expression in many tissues of apoE-deficient mice, mice with homozygous deletion of both the apoE and LDLR genes showed wild-type levels of gene transfer efficiency. Thus, a secondary event, produced by homozygous deletion of apoE, but compensated for by the concomitant deletion of LDLR, and/or effects resulting from strain-related, genetic background differences, appeared to play a significant role in mediating intravenous, CLDC-based gene delivery. Secondary alterations resulting from germ line knockouts, as well as epigenetic effects produced by strain differences, may limit the ability to assign specific, gene transfer-related functions to the deleted gene.

Intraluminal water increases expression of plasmid DNA in rat lung.

Effective gene delivery to specific organs is a major goal for human gene therapy. The lung's structure allows instillation of agents into the airspaces, directly adjacent to the lung epithelium. We hypothesized that the airspace instillation of hypotonic solutions would increase the permeability of the lung epithelium and increase DNA uptake. This hypothesis was tested by instilling plasmid DNA (p4241) encoding the luciferase gene in isotonic and hypotonic solutions. The highest luciferase expression in the lung was achieved after the instillation of this plasmid DNA in distilled water. Aerosolization of water just before the instillation of the plasmid DNA also enhanced the expression level of luciferase in the lung. In addition, an intralobar instillation of the plasmid DNA in water significantly increased the luciferase expression, suggesting that the instillation of the plasmid over a smaller surface area increased expression. Levels of expression could be measured for 3 days. Water increases the permeability of lung epithelial cells transiently and/or enhances gene expression and can be used to achieve gene expression in the lung airspaces for short intervals without toxicity.

Gene expression along the cerebral-spinal axis after regional gene delivery.

We demonstrate here that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or cationic liposome: DNA complexes (CLDCs) produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Gene expression was identified both within the spinal cord and the brain after intracerebroventricular or intrathecal injection of either CLDCs or plasmid DNA alone. Intracerebroventricular or intrathecal injection of CLDCs containing the beta-galactosidase (beta-Gal) gene produced patchy, widely scattered areas of beta-Gal expression. The chloramphenicol acetyltransferase (CAT) reporter gene product reached peak levels between 24 hr and 1 week postinjection, and was still present at significant levels 3 weeks after a single intracerebroventricular or intrathecal injection. Intrathecal injection of the human granulocyte colony-stimulating factor (G-CSF) gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine nerve growth factor (NGF) gene increased mNGF levels in the hippocampus, a target region for cholinergic neurons in the medial septum, and increased cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) activity within the brain, a well-characterized effect of both purified and recombinant NGF protein. These findings indicate that intracerebroventricular or intrathecal injection of CLDCs can produce significant levels of expression of biologically and therapeutically relevant genes within the CNS. Efficient gene transfer into the CNS will facilitate the evaluation of gene function and regulation within the brain and spinal cord. We attempted to transfer and express genes within the brain and spinal cord by direct CNS injection of either DNA alone or CLDCs into the intraventricular and subarachnoid compartments. We show that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or CLDCs produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Intrathecal injection of the hG-CSF gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine NGF gene increased mNGF levels in the hippocampus, and increased cholinergic neurotransmitter synthetic enzyme ChAT activity within the brain. Locoregional diffusion of gene products expressed by transfected meningeal lining cells into brain and spinal cord parenchyma could potentially target secreted proteins within brain and spinal cord regions relevant to neuropathological states while limiting peripheral side effects.

Topical gene delivery to murine skin.

We topically applied naked plasmid DNA containing the luciferase or chloramphenicol acetyltransferase cDNA directly to mouse skin. Gene expression was detected in skin samples as early as 4 h after DNA application, plateaued from 16 to 72 h post-application, and had decreased significantly by 7 d post-application. Reporter gene activity following topical DNA delivery was comparable with that produced by intradermal injection of DNA. Plasmid DNA at concentrations > or =0.25 microg per microl were required to achieve maximal expression levels. Reporter gene expression following topical administration was largely confined to the superficial layers of the epidermis and to hair follicles. Surprisingly, certain cationic liposomes inhibited the efficiency of cutaneous gene transfer. This technique provides a simple, clinically relevant approach to deliver genes to the skin, with potential application in treating a variety of cutaneous disorders.

Efficient gene expression in skin wound sites following local plasmid injection.

Transfection of the skin by local gene delivery, as well as widespread transfection of systemic tissues following intravenous injection of cationic liposome/DNA complexes have been reported. Here, we show that surgically wounded mouse skin can be transfected either by local injection of DNA alone or by intravenous injection of optimized cationic liposome/DNA complexes; however, direct cutaneous injection produces much higher levels of gene expression in the skin, which is targeted to dermal and subdermal layers. High levels of chloramphenicol acetyltransferase activity were present from 3 h to 2 wk following direct injection of a gene expression plasmid into wounded skin and were maintained at detectable levels up to 8 wk after injection. Expression of transferred chloramphenicol acetyltransferase as well as beta-GAL genes was localized to fibroblasts, macrophages, and adipocytes as determined by histochemistry and immunohistochemistry. Further- more, local injection of a human granulocyte- colony-stimulating factor gene expression plasmid produced high levels of the biologically relevant human granulocyte-colony-stimulating factor protein in wounded mouse skin. This efficient and simple method of site-specific gene transfer into wounds may lead to the development of cutaneous gene therapy directed against disorders of abnormal cutaneous wound healing.

Cytokine-activated human monocytes show differential cytotoxicity toward fresh and cultured Kaposi's sarcoma cells.

We have examined the ability of peripheral blood monocytes (PBMs) isolated from AIDS-related Kaposi's sarcoma (KS) patients or normal donors to kill (a) autologous KS tumor cells from skin biopsies of AIDS patients, (b) a tumorigenic cell line derived from a histologically verified AIDS-KS skin tumor, and (c) the WEHI-164 fibrosarcoma line. Unstimulated PBMs, and PBMs activated by IFNs, IL-2, or TNF-alpha, were tested for their ability to lyse 51Cr-labeled tumor targets. PBMs from both normal and KS patients, when activated by cytokines, showed enhanced cytolysis of both WEHI-164 and the KS cell line. PBMs from two of three AIDS patients lysed their autologous fresh KS tumor cells. These results indicate that PBMs from AIDS-KS patients can be induced by cytokines to elicit potent antitumor activity, including cytolysis of autologous KS tumor cells.