Decrease In Cell Mass Research Articles

TSPO in pancreatic beta cells and its possible involvement in type 2 diabetes

Amyloidosis forms a large family of pathologies associated with amyloid deposit generated by the formation of amyloid fibrils or plaques. The amyloidogenic proteins and peptides involved in these processes are targeted against almost all organs. In brain they are associated with neurodegenerative disease, and the Translocator Protein (TSPO), overexpressed in these inflammatory conditions, is one of the target for the diagnostic. Moreover, TSPO ligands have been described as promising therapeutic drugs for neurodegenerative diseases. Type 2 diabetes, another amyloidosis, is due to a beta cell mass decrease that has been linked to hIAPP (human islet amyloid polypeptide) fibril formation, leading to the reduction of insulin production. In the present study, in a first approach, we link overexpression of TSPO and inflammation in potentially prediabetic patients. In a second approach, we observed that TSPO deficient rats have higher level of insulin secretion in basal conditions and more IAPP fibrils formation compared with wild type animals. In a third approach, we show that diabetogenic conditions also increase TSPO overexpression and IAPP fibril formation in rat beta pancreatic cell line (INS-1E). These data open the way for further studies in the field of type 2 diabetes treatment or prevention.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Anemia tolerance

Anemia is a pathological condition in which the hemoglobin and red blood cell mass decrease; it is mainly defined by the concentration of hemoglobin in the blood. The World Health Organization guidelines establish specific values to define anemia in different population groups. Early detection of anemia can also be a valuable indicator of underlying medical conditions. Clinical studies have explored the relationship between perioperative anemia and morbidity, highlighting the need for more judicious therapeutic strategies, such as the use of Patient Blood Management, which aims to prevent and treat anemia in a personalized and effective way. Patient Blood Management emerges as a promising approach to dealing with anemia, recognizing that its correction through transfusion always carries risks and that personalized prevention and treatment can offer better outcomes for patients.

Effect of mangosteen skin ethanol extract on streptozotocin-induced TNF-α expression

Introduction. Diabetes Mellitus (DM) is a significant health problem worldwide. DM with poor control of blood glucose levels can eventually cause pancreatic cell disorders, including a decrease in cell mass and function. Mangosteen rind contains xanthone compounds that can be used to protect and reduce cell damage, especially those caused by free radicals. This study aimed to analyze the administration of mangosteen peel ethanol extract on the expression of TNF-α induced by streptozotocin. Materials and Methods. The research was carried out in an experimental laboratory. The research design used was Randomized Post Test Only Control Group Design. The sample is a male rat Wistar strain. Rats were grouped into five groups, namely negative control group, positive control STZ, mangosteen peel extract at a dose of 200 mg/kg BW (K2), a dose of 400 mg/kg BW (K3), an amount of 600 mg/kg BW (K4). Administration of therapy for 14 days orally. Results. The effects of the mangosteen rind extract had a lower TNF- positive cell count of 3.83 compared to the group that was not treated with the mangosteen rind extract 19.33. All treatment groups showed a significant difference (P<0.001) in the number of TNF- protein-expressing cells. This research can inform the public that mangosteen peel’s benefits can be developed as prevention and alternative treatment in humans caused by inflammation. Conclusions. This research affects the administration of ethanol extract of mangosteen peel to decrease the number of TNFpositive cells with an effective dose of 600 mg/kg BW.

Body composition in sarcopenia in middle-aged individuals

to evaluate the parameters of body composition in the early diagnosis of sarcopenia in middle-aged people. The participants were divided into two groups - the main one with sarcopenia - 146 people and the control group - 75 people. The complex of examinations included: neuropsychological testing (Hospital Anxiety and Depression Scale (HADS), quality of life questionnaire for patients with sarcopenia (SarQoL), short health assessment form (SF-36)), 4-meter walking speed test, dynamometry and bioimpedancemetry. The results of neuropsychological examination did not differ in the main and control groups. Patients with sarcopenia showed a decrease in muscle strength according to dynamometry. The scores of the walking speed assessment test in the study group were significantly higher than in the control group. The main and control groups had excessive body weight. According to the results of bioimpedanceometry, the main group had increased fat mass, percentage of fat mass, visceral fat area, and fat mass index compared with the control group. Skeletal muscle mass was less in the main group, probable sarcopenia was confirmed by decreased appendicular mass, decreased protein and mineral content was also recorded. There was a more pronounced decrease in cell mass in the main group. In patients with sarcopenia the volume of intracellular and extracellular fluid was less than in the control group. Significant differences were considered at p<0.05. the introduction of bioimpedancemetry and dynamometry into early screening for muscle mass reduction will allow timely start of therapeutic and preventive measures even in middle age, which will lead to a decrease in the progression of sarcopenia in the elderly, as well as improve the quality of life.

Screening-level evaluation of marine benthic dinoflagellates toxicity using mammalian cell lines.

Complementary studies at different levels of the biological organization are fundamental to fully link environmental exposure to marine benthic dinoflagellate toxins and their effects. In order to contribute to this transdisciplinary evaluation, and for the first time, the present study aims to study the effects of Gambierdiscus excentricus, Ostreopsis cf. ovata, Prorocentrum hoffmannianum and Prorocentrum lima extracts on seven functionally different mammalian cell lines: HEK 293, HepG2, HNDF, H9c2(2-1), MC3T3-E1, Raw 264.7 and SH-SY5Y. All the cell lines presented cell mass decrease in a concentration-dependence of dinoflagellate extracts, exhibiting marked differences in cell toxicity. Gambierdiscus excentricus presented the highest effect, at very low concentrations with EC50,24h (i.e., the concentration that gives half-maximal response after a 24-h exposure) between 1.3 and 13cells mL-1, followed by O. cf. ovata (EC50,24h between 3.3 and 40cells mL-1), and Prorocentrum species (P. lima: EC50,24h between 191 and 1027cells mL-1 and P. hoffmannianum: EC50,24h between 152 and 783cells mL-1). Cellular specificities were also detected and rat cardiomyoblast H9c2(2-1) cells were in general the most sensitive to dinoflagellate toxic compounds, suggesting that this cell line is an animal-free potential model for dinoflagellate toxin testing. Finally, the sensitivity of cells expressing distinct phenotypes to each dinoflagellate extract exhibited low relation to human poisoning symptoms.

Osmotolerance in Escherichia coli Is Improved by Activation of Copper Efflux Genes or Supplementation with Sulfur-Containing Amino Acids

Improvement in the osmotolerance of Escherichia coli is essential for the production of high titers of various bioproducts. In this work, a cusS mutation that was identified in the previously constructed high-succinate-producing E. coli strain HX024 was investigated for its effect on osmotolerance. CusS is part of the two-component system CusSR that protects cells from Ag(I) and Cu(I) toxicity. Changing cusS from strain HX024 back to its original sequence led to a 24% decrease in cell mass and succinate titer under osmotic stress (12% glucose). When cultivated with a high initial glucose concentration (12%), introduction of the cusS mutation into parental strain Suc-T110 led to a 21% increase in cell mass and a 40% increase in succinate titer. When the medium was supplemented with 30 g/liter disodium succinate, the cusS mutation led to a 120% increase in cell mass and a 492% increase in succinate titer. Introducing the cusS mutation into the wild-type strain ATCC 8739 led to increases in cell mass of 87% with 20% glucose and 36% using 30 g/liter disodium succinate. The cusS mutation increased the expression of cusCFBA, and gene expression levels were found to be positively related to osmotolerance abilities. Because high osmotic stress has been associated with deleterious accumulation of Cu(I) in the periplasm, activation of CusCFBA may alleviate this effect by transporting Cu(I) out of the cells. This hypothesis was confirmed by supplementing sulfur-containing amino acids that can chelate Cu(I). Adding methionine or cysteine to the medium increased the osmotolerance of E. coli under anaerobic conditions.IMPORTANCE In this work, an activating Cus copper efflux system was found to increase the osmotolerance of E. coli In addition, new osmoprotectants were identified. Supplementation with methionine or cysteine led to an increase in osmotolerance of E. coli under anaerobic conditions. These new strategies for improving osmotolerance will be useful for improving the production of chemicals in industrial bioprocesses.

Quantifying Cellular Elasticity using Quantitative Phase Microscopy Measurements of Electromagnetically Actuated Magnetic Microsphere Indentation

Metastasis is responsible for 90% of cancer cell deaths, and mechanical properties of cancer cells are an important and emerging indicator of cancer cell metastatic potential. Therefore, screening the mechanical properties of cancer cells, alone and in response to chemotherapy, provides an important indicator of disease progression and drug effectiveness. There are many existing approaches to measuring cell mechanical properties, however the mechanical constraints of these systems cannot be readily combined with measurements of cell growth or death to quantify the full response of cancer cells to potential therapies. Quantitative phase microscopy (QPM) is an established approach for determining the growth response of cancer cells to a variety of chemotherapies, from small-molecule inhibitors to adoptive immunotherapies, by quantifying the rate of increase or decrease in cell mass over time. In this work we describe a system based on QPM that quantifies cell mechanical properties using an Arudino microcontroller to control electromagnet-driven oscillation and indentation of magnetic nickel microspheres distributed on top of adherent cells in vitro. QPM measures cell mass as well as magnetic microsphere indentation and relaxation over time, and can therefore simultaneously quantify cell growth, stiffness, and viscosity. Electromagnet actuation allows for rapid modulation of the indentation force applied to cells for simultaneous, high-throughput measurements of mechanical responses at up to several hundred locations within each field of view. In combination with the ability of QPM to rapidly determine the effects of chemotherapeutics on cancer cell growth, this system will enable selection of treatments to better target both the growth and mechanical properties of cancer cells, in an effort to select and design optimal chemotherapeutic strategies to combat metastasis.

Quantifying Biomass Changes of Single CD8+ T Cells during Antigen Specific Cytotoxicity

Existing approaches that quantify cytotoxic T cell responses rely on bulk or surrogate measurements which impede the direct identification of single activated T cells of interest. Single cell microscopy or flow cytometry methodologies typically rely on fluorescent labeling, which limits applicability to primary cells such as human derived T lymphocytes. Here, we introduce a quantitative method to track single T lymphocyte mediated cytotoxic events within a mixed population of cells using live cell interferometry (LCI), a label-free microscopy technique that maintains cell viability. LCI quantifies the mass distribution within individual cells by measuring the phase shift caused by the interaction of light with intracellular biomass. Using LCI, we imaged cytotoxic T cells killing cognate target cells. In addition to a characteristic target cell mass decrease of 20–60% over 1–4 h following attack by a T cell, there was a significant 4-fold increase in T cell mass accumulation rate at the start of the cytotoxic event and a 2–3 fold increase in T cell mass relative to the mass of unresponsive T cells. Direct, label-free measurement of CD8+ T and target cell mass changes provides a kinetic, quantitative assessment of T cell activation and a relatively rapid approach to identify specific, activated patient-derived T cells for applications in cancer immunotherapy.

Valosin-containing Protein (VCP) in Novel Feedback Machinery between Abnormal Protein Accumulation and Transcriptional Suppression

Abnormal protein accumulation is often observed in human neurodegenerative disorders such as polyglutamine diseases and Parkinson disease. Genetic and biochemical analyses indicate that valosin-containing protein (VCP) is a crucial molecule in the pathogenesis of human neurodegenerative disorders. We report here that VCP was specifically modified in neuronal cells with abnormal protein accumulation; this modification caused the translocation of VCP into the nucleus. Modification-mimic forms of VCP induced transcriptional suppression with deacetylation of core histones, leading to cell atrophy and the decrease of de novo protein synthesis. Preventing VCP nuclear translocation in polyglutamine-expressing neuronal cells and Drosophila eyes mitigated neurite retraction and eye degenerations, respectively, concomitant with the recovery of core histone acetylation. This represents a novel feedback mechanism that regulates abnormal protein levels in the cytoplasm during physiological processes, as well as in pathological conditions such as abnormal protein accumulation in neurodegenerations.

Bioethanol Production from Uncooked Raw Starch by Immobilized Surface-engineered Yeast Cells

Surface-engineered yeast Saccharomyces cerevisiae codisplaying Rhizopus oryzae glucoamylase and Streptococcus bovis alpha-amylase on the cell surface was used for direct production of ethanol from uncooked raw starch. By using 50 g/L cells during batch fermentation, ethanol concentration could reach 53 g/L in 7 days. During repeated batch fermentation, the production of ethanol could be maintained for seven consecutive cycles. For cells immobilized in loofa sponge, the concentration of ethanol could reach 42 g/L in 3 days in a circulating packed-bed bioreactor. However, the production of ethanol stopped thereafter because of limited contact between cells and starch. The bioreactor could be operated for repeated batch production of ethanol, but ethanol concentration dropped to 55% of its initial value after five cycles because of a decrease in cell mass and cell viability in the bioreactor. Adding cells to the bioreactor could partially restore ethanol production to 75% of its initial value.

Thermal sensitization through ROS modulation: A strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy

The purpose of this study was to investigate whether modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. HT-29 colon cancer cells were exposed to heat (43 degrees C) in the presence of the ROS-generating drug, 2-2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37 degrees C (42% vs 20%, P < .05). ROS levels were increased modestly with AAPH at 37 degrees C, whereas they increased significantly in a dose-dependent manner with AAPH at 43 degrees C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43 degrees C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43 degrees C was abrogated with AAPH exposure. Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

Effect of methotrexate on cell proliferation in developing hamster molar tooth germs in vitro.

Amongst the most frequently used drugs for the treatment of acute lymphoblastic leukaemia (ALL) belongs methotrexate (MTX), an inhibitor of pyrimidine (thymidine) synthesis. We examined effects of MTX on cell proliferation during tooth morphogenesis in organ culture by exposing hamster molar tooth germs to 10(-7) to 10(-3) M MTX for 24 h. In the presence of serum, only the highest concentration of MTX (10(-3) M) induced a small, nonsignificant decrease in cell mass without histological changes but, unexpectedly, increased uptake of [3H]thymidine. In serumless conditions increase in cell mass (dry weight) and incorporation of [3H]thymidine was lower than in serum-supplemented conditions. Exposure to MTX in serumless conditions reduced the increase in cell mass even further without histological changes and, again, strongly enhanced incorporation of [3H]thymidine to the same proportion as measured in the serum-supplemented cultures exposed to MTX. The data suggest that only exposure to high levels of MTX reduces proliferation activity, shown by reduction in cell mass. The enhanced [3H]thymidine uptake under MTX exposure was explained by blockage of the internal biosynthesis of thymidine, by which action more radiolabel was taken up from the medium. The data also suggest that serum contains (growth) factors that stimulate cell proliferation, thereby increasing cell mass and [3H]thymidine incorporation.

Effects of bacitracin and excess Mg 2+ on submerged mycelial growth of Streptomyces azureus

Effects of bacitracin (BC) and excess Mg 2+ on pellet formation and mycelial growth of Streptomyces azureus were studied in a liquid culture using Bennett medium. The addition of Mg 2+ at concentrations above 0.2 mM to the medium resulted in the promotion of pellet formation, a distinct inhibition of growth and decrease in cell mass. BC changed the growth type of mycelia from the compact pellet-type to the dispersed-type, and stimulated mycelial growth after a long lag period, accompanied by an increase in cell mass. In the presence of less than 0.2 mM Mg 2+, BC completely inhibited mycelial growth. Ca 2+ showed an effect similar to Mg 2+. EDTA inhibited pellet formation, but never stimulated growth. Furthermore, EDTA suppressed the growth inhibitory and stimulatory actions of BC. From these results, we speculated that: (i) excess Mg 2+ induced pellet formation; (ii) BC, similar to EDTA chelated with excess Mg 2+ in the medium, leading to the inhibition of pellet formation; and (iii) BC-induced stimulation of growth might be due to its chelating and antimicrobial activities. It was also said that the growth inhibitory action of BC on S. azureus was antagonized by excess Mg 2+ or Ca 2+ and EDTA.

Effects of patient age on muscle relaxant

HE AGING process has a profound effect on the actions of many drugs including the nondepolarizing muscle relaxants. This fact has long been appreciated by anesthesiologists. As early as 1957, Foldes stated that adequate operating conditions in the elderly can be achieved with smaller milligrams per kilogram doses of relaxants than in young adults of corresponding weight.l He further recommended that the initial dose of the relaxant should be reduced by two thirds to one half of the usual adult dose. Although Foldes' clinical observations concerning the use of relaxants in the elderly were widely accepted, there were no careful clinical studies to support these observations. The lack of such studies was appreciated. Bender, in a 1964 review of the pharmacological effects of aging on drug activity, stated that one of the most important reasons for writing the review was attempt to stimulate further interest in the study of the role of aging [on drug activity]--and to stress the lack of studies in man. ''z A breakthrough came in the 1970s with the development of numerous analytical methods to accurately measure concentration of the relaxants in man. There followed an efflorescence of studies on the distribution, elimination, and actions of muscle relaxants in man. Once pharmacokinetic and pharmacodynamic values had been established for the normal human, investigators' attention was directed to studies of both pathological and physical states, in which the pharmacokinetics and pharmacodynamics of muscle relaxants might vary from the normal state. The effects of increasing age on the pharmacology of muscle relaxants attracted wide attention for several reasons. First, a number of review articles were published focusing on alteration in body composition and function with age and their possible effect on drug therapy in the elderly. 3-8 Secondly, we are an aging population. This is especially appreciated by one of the authors (RSM) of this review, who will soon become a senior citizen. At the present time, approximately 12% of the United States population is over the age of 65, and one third of all hospital beds in this country are occupied by the elderly. The elderly have become such a large segment of our population that gerontologists have subdivided the elderly (persons over age 65) into subgroups. One of the subgroups, the very elderly (over age 85), is in fact the fastest growing segment of our population. The changes are reflected in the type of patients we as anesthesiologists see in our practice. In our own clinic, Columbia Presbyterian Medical Center, a decade ago, 15% of patients undergoing anesthesia were age 70 or older. Today this figure approaches 20%. This review examines the pathophysiological changes that normally accompany advancing age (Table 1), and then examine how these changes affect the distribution, elimination (pharmacokinetics), and actions (pharmacodynamics) of the nondepolarizing muscle relaxants. DISTRIBUTION Two changes that may have a profound effect on drug distribution are the decrease in lean body mass (20% to 25%) and the increase in body fat (50% to 75%) seen with advancing years. 9'~~ There is a sex difference between these two tissues in that women have more fat and less lean body mass than men at any age, but the trend toward an increase in body fat with aging is the same in both sexes. These changes could cause a decrease in the distribution of water-soluble drugs (such as the muscle relaxants) and an increase in the distribution of fat-soluble drugs. Total body water has also been shown to increase significantly with age TM (up to 15%). This is accompanied by a decrease in cell mass. 9 Ritschel 4 has pointed out

The Dictyostelium cell cycle and its relationship to differentiation

The dictyostelium vegetative cell cycle is characterized by a short mitotic period followed immediately by a short S-phase (less than 30 min) and a long and variable G2 phase. The cell cycle continues during differentiation despite a decrease in cell mass: DNA replication and mitosis occur early in development and also at the tipped aggregate stage. Cells that are in mitosis, S-phase or early G2, when starved differentiate into prestalk cells and cells that are in the middle of G2 differentiate into prespore cells. We postulate that there is a restriction point late in the G2 phase, about 1-2 h before mitosis, where the cells can be arrested either by starvation and the initiation of development, by growing into stationary phase, or by prolonged incubation at low temperature. During development, this block persists to the tipped aggregate stage, where it is specifically released in prespore cells, and these cells then go through one more round of cell division. Genes encoding components of the cell cycle machinery have recently been isolated and attempts to specifically block the cell cycle by reverse genetics to study the effects on differentiation have been initiated.

The Dictyostelium cell cycle and its relationship to differentiation.

The dictyostelium vegetative cell cycle is characterized by a short mitotic period followed immediately by a short S-phase (less than 30 min) and a long and variable G2 phase. The cell cycle continues during differentiation despite a decrease in cell mass: DNA replication and mitosis occur early in development and also at the tipped aggregate stage. Cells that are in mitosis, S-phase or early G2, when starved differentiate into prestalk cells and cells that are in the middle of G2 differentiate into prespore cells. We postulate that there is a restriction point late in the G2 phase, about 1-2 h before mitosis, where the cells can be arrested either by starvation and the initiation of development, by growing into stationary phase, or by prolonged incubation at low temperature. During development, this block persists to the tipped aggregate stage, where it is specifically released in prespore cells, and these cells then go through one more round of cell division. Genes encoding components of the cell cycle machinery have recently been isolated and attempts to specifically block the cell cycle by reverse genetics to study the effects on differentiation have been initiated.

Alterations in Body Composition after Gastroplasty for Morbid Obesity

Body compositional changes during rapid weight loss and after weight stabilization were prospectively studied in morbidly obese patients undergoing gastroplasty operations. Body composition was studied preoperatively and 6 and 24 months postoperatively in 23 patients by use of a total body counter (40K) and an isotope dilution technique. The mean fat mass, cell mass, and intracellular water (ICW) decreased during the first 6 months (p less than 0.001) and remained unchanged at the 24-month test. However, the mean liters of extracellular water (ECW) did not change. Consequently, the ECW/ICW ratio, high in states of malnutrition, rose above postoperative levels. A strong correlation was found between decreases in cell mass and increases in the ECW/ICW ratio.

Localization of cholesterol synthesis along villus-crypt axis in diabetic rats

In diabetic animals cholesterol synthesis is increased in the small intestine, and this increase occurs in all segments along the duodenal-ileal axis. In the present study we have determined the sites along the villus-crypt axis in which cholesterol synthesis is increased. In diabetic animals cholesterol synthesis is increased in the proximal small intestine, and this is chiefly due to an increased synthesis in the crypt cells. In the midintestine cholesterol synthesis is increased in all cell fractions, but again the crypt cells are the major site accounting for the increase. In the distal small intestine synthesis is increased in all cell fractions, but the increase is greatest in the upper villus cells. Thus the basis for the increase in intestinal cholesterol synthesis in diabetic animals is dependent on location. Additionally, in the proximal small intestine the increase in synthesis is due to an increased mass of cells, whereas in the distal small intestine the increase is due to an increased synthesis per unit of tissue. In cholesterol-fed diabetic animals we observed a decrease in cholesterol synthesis in the proximal and midintestine that was due to a decrease in synthesis in all cell fractions. This decrease in synthesis is accounted for by a decrease in synthesis per unit of tissue. Restricting food intake in the diabetic animals decreased cholesterol synthesis in all cell layers, and this decrease is due to a decrease in cell mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased erythropoiesis: the origin of the BCG induced anaemia in mice.

Transient anaemia follows a high dose of viable BCG given intravenously to mice. The anaemia was dependent upon the dose, viability and the route of injection of the BCG. The evidence of an absolute anemia was based on red cell mass decrease. Serum iron concentration and red cell life span were unchanged in the first 14 d after BCG infection. The erythropoietin level increased 20-fold. Despite the high level of this hormone and the appearance of increased erythropoiesis in the spleen, the production of erythrocytes was decreased presumably because of a decrease in numbers of erythropoietin-responsive cells.

The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy

A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2′-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2′-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration.