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Quantitative studies on fabrics as disseminators of viruses. 3. Persistence of vaccinia virus on fabrics impregnated with a virucidal agent.

Eight compounds were tested in vitro for virucidal and antiviral activity against poliovirus and vaccinia virus. These compounds included five quaternary ammonium salts, two bromosalicylanilides, and neomycin sulfate, an antibiotic. None of the compounds was active against poliovirus, but virucidal activity was demonstrated against vaccinia virus with three of the quarternary ammonium compounds: n-alkyl (C14, C12, C16) dimethyl benzyl ammonium chloride, di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate, and n-alkyl (60% C14, 30% C16, 5% C12, 5% C18) dimethyl benzyl ammonium chlorides plus n-alkyl (50% C12, 30% C14, 17% C16, 3% C18) dimethyl ethylbenzyl ammonium chlorides. Wool blanketing, wool gabardine, and cotton sheeting materials were impregnated with the first of the above virucidal compounds, and the persistence of vaccinia virus on these fabrics was compared with the persistence of the agent on nonimpregnated fabrics of the same type held at 25 C in 35 and 78% relative humidity. No virus could be recovered from the chemically treated fabrics at any time after virus exposure, whereas the virus persisted as long as 4 weeks on nonimpregnated materials. Viable vaccinia virus was also found to persist less than 1 day on a cotton fabric finished with a wash-and-wear modified triazone resin. Poliovirus persisted less than 5 days on this wash-and-wear fabric.

Anilides↗

Mechanism of Helicobacter pylori-associated gastric mucosal injury.

Helicobacter pylori infection is associated with gastric mucosal damage and the infiltration of neutrophils. Myeloperoxidase from neutrophils produces hypochlorous acid, which yields monochloramine in the presence of ammonia produced by urease enzyme of Helicobacter pylori. The target cells of gastric mucosal damage are gastric mucosal cells and endothelial cells. We therefore tested the hypothesis that ammonium, hypochlorous acid, and monochloramine damage the target cells. We studied the in vitro cytotoxic effects of ammonium chloride, sodium hypochlorite, monochloramine, and activated neutrophils on the target cells. Cytotoxicity was measured by a 51Cr-release assay. Ammonium chloride, sodium hypochlorite, and monochloramine were toxic to labeled cells in a concentration dependent manner. The toxicity of these agents was in the order monochloramine > sodium hypochlorite >> ammonium chloride. Incubation of labeled cells with activated neutrophils, Helicobacter pylori, and urea resulted in cytolysis. These cytotoxicities were significantly inhibited by the scavenger of hypochlorous acid, taurine. Monochloramine is more toxic to the target cells than ammonium chloride. Although ammonium chloride at neutral pH by itself has little direct damaging effect on the gastric mucosa, it is damaging to the gastric mucosa through a reaction with hypochlorous acid, suggesting that it plays a role in Helicobacter pylori-associated gastric damage.

Animals↗

Intracellular pH on adrenergic-stimulated cAMP and cGMP production in rat pinealocytes.

In rat pinealocytes, activation of alpha 1-adrenergic receptors leads to increases in intracellular pH (pHi). In this study, the role of pHi on adrenergic regulation of cyclic nucleotide accumulation was investigated using ammonium chloride, which increased pHi, and sodium propionate, which reduced pHi. Ammonium chloride significantly enhanced the norepinephrine-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) responses, while it selectively potentiated the isoproterenol (ISO)-stimulated cGMP response. Reduction of pHi by sodium propionate reduced the norepinephrine-stimulated cGMP accumulation by 70%, and its effect on the ISO-stimulated cGMP response was stimulatory. Treatment with sodium propionate effectively neutralized the enhancing effects of ammonium chloride on the adrenergic-stimulated cAMP and cGMP responses. These effects of sodium propionate and ammonium chloride on cyclic nucleotides appeared to reflect altered rate of synthesis, and they were also in part secondary to changes in intracellular Ca2+. Our findings indicate that the receptor-mediated changes in pHi may play an integral part in the adrenergic regulation of cAMP and cGMP production in rat pinealocytes.

Ammonium Chloride↗

Pongamia pinnata modulates the oxidant-antioxidant imbalance in ammonium chloride-induced hyperammonemic rats.

The effect of Pongamia pinnata (an indigenous plant used in Ayurvedic Medicine in India) leaf extract (PPEt) on circulatory lipid peroxidation and antioxidant status was evaluated in ammonium chloride-induced hyperammonemic rats. Enhanced lipid peroxidation in the circulation of ammonium chloride-treated rats was accompanied by a significant decrease in the levels of vitamin A, vitamin C, vitamin E, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). PPEt-administered rats experienced a significant reduction in lipid peroxidation with a simultaneous elevation in antioxidant levels. Our results indicate that PPEt modulates these changes by reversing the oxidant-antioxidant imbalance during ammonium chloride-induced hyperammonemia and this could be due to its (i) antihyperammonemic effect by means of detoxifying excess ammonia, urea and creatinine and (ii) antioxidant property. The exact mechanism has to be still investigated and isolation of active constituents is required.

Ammonium Chloride↗

Column preconcentration of gold by adsorbing AuCl4- onto methyltrioctyl ammonium chloride-naphthalene and subsequent atomic absorption spectrometric determination.

A sensitive, selective and simple preconcentration method for ultra-trace gold determination has been developed that uses naphthalene-methyltrioctyl ammonium chloride (Aliquat 336s) as an adsorbent. Gold, in the form of AuCl4-, was retained by the adsorbent in the column at a flow rate of 1 ml min(-1). After filtration, the solid mass consisting of the gold complex and naphthalene was dissolved out of the column with 5 ml of N,N-dimethylformamide (DMF), and the metal was then determined by atomic absorption spectrometry. In the initial solution, the calibration graph of absorbance versus gold concentration was found to be linear in the range 0.5-150 ng ml(-1) Au(III) with r=0.997 (n=9), and the 3 s detection limit was 0.428 ng ml(-1). The relative standard deviation for eight replicate measurements of 20 microg of gold was 2.14%. Preconcentration factors of 390 and 650 were achieved using 5 ml and 3 ml of DMF, respectively. The proposed method was successfully applied to the determination of gold in wastewater, processed pool water, slurry pool water, and raw well-water from the Moteh gold mine, and synthetic samples.

Journal Article↗

Stimulation of tyrosinase activity of cultured melanoma cells by lysosomotropic agents.

The tyrosinase (EC 1.14.18.1) activity of cell-free extracts (TyH) of B16 melanoma cells cultured in the presence of 5 to 10 mM ammonium chloride was considerably higher than that of cells from control cultures. This increase in TyH in the presence of ammonium chloride seemed to be due to de novo synthesis of the enzyme, because it was inhibited by 1 microgram/ml of cycloheximide. In the presence of the latter, however, ammonium chloride did increase the tyrosinase activity of living cells in culture (TyC) resulting in about threefold increase in the TyC/TyH ratio, a measure of the extent of tyrosinase reaction exerted by the enzyme present in living cells. This higher TyC/TyH ratio induced by ammonium chloride was also observed in the absence of cycloheximide. Similar increases in TyH, TyC, and TyC/TyH occurred in the presence of methylamine or ethylamine instead of ammonium chloride, but not in the presence of tetraethylammonium chloride, and also in culture medium of higher pH. The apparently similar effects of lysosomotropic bases and medium of higher pH on the TyC/TyH ratio suggest that there are some mechanisms that control the intramelanosomal pH lower than the cytoplasmic pH.

Ammonium Chloride↗

Interaction of cultured mammalian cells with [125I] diphtheria toxin.

The characteristics of cell adsorption and pinocytotic uptake of diphtheria toxin by several mammalian cell types were studied. Purified toxin iodinated by a solid-state lactoperoxidase method provided preparations of high specific activity and unaltered biological activity. Dephtheria toxin-sensitive HEp-2 cells and guinea pig macrophage cultures were compared with resistant mouse L-929 cells. At 37 C the resistant cells in monolayer adsorbed and internalized [125I] toxin to a greater extent than did the HEp-2 cell cultures; no significant differences were observed at 5 C. Ammonium chloride protection levels did not alter uptake of toxin by either L-929 OR HEp-2 cells. Biological activity of the iodinated toxin, however, was negated provided the presence of ammonium chloride was maintained. The ammonium salt appears to maintain toxin in a state amenable to antitoxin neutralization. Guinea pig macrophages internalized iodinated toxin to a level 10 times greater than the established cell lines. In spite of the increased uptake of toxin by the endocytic cells, ammonium chloride prevented expression of toxicity. In an artificial system, toxin adsorbed to polystyrene latex spheres and internalized by guinea pig macrophages during phagocytosis did express biological activity. Ammonium chloride afforded some but not total protection against toxin present in the phagocytic vacuoles. The data suggest that two mechanisms of toxin uptake by susceptible cells may be operative. Toxin taken into the cell by a pinocytotic process probably is not ordinarily of physiological significance since it is usually degraded by lysosomal enzymes before it can reach cytoplasmic constituents on which it acts. When large quantities of toxin are pinocytized, toxicity may be expressed before enzymatic degradation is complete. A more specific uptake involving direct passage of the toxin through the plasma membrane may be the mechanism leading to cell death in the majority of instances.

Adsorption↗

Binding and degradation of [125I]human growth hormone in rat adipocytes.

Iodinated human GH [( 125I]hGH) binds to both specific and nonspecific sites on the surface of adipocytes isolated from the epididymal fat of normal rats. When adipocytes were incubated at 37 C with 1 nM [125I]hGH, specific binding increased for 30-60 min and thereafter remained approximately constant as long as the hormone was present in the medium. When cells that had bound [125I]hGH were removed from the incubation medium and reincubated in hormone-free medium at 37 C, half of the specifically bound 125I was released into the medium about every 30 min, and about half of the nonspecifically bound 125I was released in about 60 min. These rates were seen regardless of whether the time allowed for hormone binding was 15, 30, or 60 min. About 90% of the 125I released was soluble in 5% trichloroacetic acid and was in the form of iodotyrosine. The rate of 125I release from specific binding sites decreased by a factor of 4 when the temperature was lowered from 37 to 17 C. Replacement of some of the sodium chloride in the buffer with 25 mM ammonium chloride had little or no effect on the amount on 125I that bound to cells when [125I]hGH was present in the medium, but virtually completely blocked the release of 125I from cells transferred to hormone-free medium. Ammonium chloride also significantly reduced both the release of 125I from nonspecific binding sites and the amount of 125I recovered in trichloroacetic acid-soluble form. Cloroquine, leupeptin, or colchicine nearly doubled the specific binding of [125I]hGH after 180 min and markedly slowed the release of 125I when cells were transferred to hormone-free medium. All of these agents also significantly reduced the rate of release of 125I from nonspecific binding sites. Incubation of adipose tissue from hypophysectomized rats with ammonium chloride, leupeptin, or colchicine failed to alter the ability of GH to increase glucose oxidation, induce refractoriness, or promote lipolysis in the presence of theophylline. We conclude that GH binds virtually irreversibly to both specific and nonspecific sites on the adipocyte surface and is then internalized and degraded in the lysosomones. These events appear to be independent of the cellular processes that lead to expression to GH responses.

Adipose Tissue↗

Characterization of N-methyl-D-aspartate receptor subunits involved in acute ammonia toxicity.

Rapid administration of large doses of ammonia leads to death of animals, which is largely prevented by pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists. The present study focuses on a subunit(s) of NMDA receptor involved in ammonia-induced death by use of NMDA receptor GluRepsilon subunit-deficient (GluRepsilon(-/-)) mice and the selective GluRepsilon2 antagonist CP-101,606. Acute ammonia intoxication was induced in mice (eight per group) by a single intraperitoneal (i.p.) injection of ammonium chloride. Appearance of neurological deteriorations depended on the doses of ammonium chloride injected. While wild-type, GluRepsilon1(-/-), GluRepsilon4(-/-), and GluRepsilon1(-/-)/epsilon4(-/-) mice all died by ammonium chloride at 12 mmol/kg during the first tonic convulsions, two of eight GluRepsilon3(-/-) mice survived. Pretreatment of wild-type mice with CP-101,606 prevented two mice from ammonia-induced death. Pretreatment of GluRepsilon3(-/-) mice with CP-101,606 prevented the death of three mice and prolonged the time of death of non-survivors. Similarly, the neuronal form of nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) as well as the nonselective NOS inhibitor L-NMMA, but not the inducible NOS inhibitor 1400W, partially prevented the death of mice and prolonged the period of death. Furthermore, ammonium chloride prolonged the increase in intracellular free Ca2+ concentration ([Ca2+]i) and subsequent NO production induced by NMDA in the cerebellum. These results suggest that activation of NMDA receptor containing GluRepsilon2 and GluRepsilon3 subunits and following activation of neuronal NOS are involved in acute ammonia intoxication which leads to death of animals.

Ammonia↗

Water, acidosis, and experimental pyelonephritis.

The effect of water restriction and ammonium chloride acidosis on the course of Escherichia coli pyelonephritis was determined in the nonobstructed kidney of the rat. To alter the chemical composition of the renal medulla, water intake was reduced in rats to one-half the normal daily intake. Water restriction increased the incidence of coliform pyelonephritis. Systemic acidosis, produced by giving a 300 mM solution of ammonium chloride, increased urinary osmolality to values comparable to water restriction and also predisposed to pyelonephritis. However, when rats were fed the same solution of ammonium chloride but were allowed access to tap water ad lib., urinary osmolality values were comparable to those observed in normal animals, and susceptibility to pyelonephritis was reduced or eliminated despite a degree of systemic acidosis similar to that observed in rats fed ammonium chloride solution without access to tap water. These results suggest that water diuresis may overcome the inactivation of complement produced by ammonium chloride acidosis and that renal medullary hypertonicity, produced by either water restriction or ammonium chloride acidosis, is a major determinant of this tissue's unique susceptibility to infection.

Acidosis↗

Adaptive and cross-adaptive responses of persistent and non-persistent Listeria monocytogenes strains to disinfectants.

Persistent and non-persistent Listeria monocytogenes strains were tested for initial resistance and adaptive and cross-adaptive responses towards two quaternary ammonium compounds, alkyl-benzyl-dimethyl ammonium chloride and n-alkyldimethyl ethylbenzyl ammonium chloride, one tertiary alkylamine, 1,3-propanediamine-N-(3-aminopropyl)N-dodecyl, sodium hypochlorite and potassium persulphate. The initial resistance of two persistent and two non-persistent L. monocytogenes strains was observed to differ. Both types of strains adapted after a 2-h sublethal exposure to the quaternary ammonium compounds and the tertiary alkylamine, the highest increase in the minimum inhibitory concentration (MIC) being 3-fold. Progressively increasing disinfecting concentrations at 10 and 37 degrees C resulted in adaptation of L. monocytogenes to all disinfectants except potassium sulphate. The highest observed increase in MIC was over 15-fold, from 0.63 to 10 microg/ml of n-alkyldimethyl ethylbenzyl ammonium chloride. All strains reached approximately similar MICs. Stability of the increased resistance was tested by measuring MICs every seventh day for 28 days. The increased resistance to sodium hypochlorite disappeared in 1 week, but the quaternary ammonium compounds and the tertiary alkylamine showed increased resistance for 28 days. These results suggest that cellular changes due to adaptive responses continue to have an effect on the resistance some time after the exposure. All disinfectants were shown to cause cross-adaptation of L. monocytogenes, the highest increase in MIC being almost 8-fold. The only agent that L. monocytogenes could not be shown to cross-adapt to was potassium persulphate which did, however, cause cross-adaptation to the other disinfectants. The mechanism behind these adaptive responses seemed to be non-specific as cross-adaptation was observed not only between related but also unrelated disinfectants. These findings suggest that sustaining high disinfectant effectiveness may be unsuccessful by rotation, even when using agents with different mechanisms of action.

Adaptation, Physiological↗

Effect of ammonia on cell-cycle progression of human gastric cancer cells.

AIM: Ammonia is a cytotoxic factor of Helicobacter pylori that is involved in gastric mucosal injury. This study was designed to show whether ammonia has an effect on the cell-cycle progression in human gastric cells in vitro. MATERIALS AND METHODS: We studied the effects of ammonia and ammonium chloride on cell growth and cell-cycle progression of the human gastric cancer cell line HGC-27. We cultured HGC-27 cells and counted viable cells by trypan blue dye exclusion 24 h after the addition of various concentrations of ammonia or ammonium chloride. DNA contents of nuclei were analysed by flow-cytometry. RESULTS: Ammonia and ammonium chloride inhibited the proliferation of HGC-27 cells dose-dependently. Flow-cytometric analysis showed S-phase accumulation of HGC-27 cells treated with ammonia and ammonium chloride at cytostatic doses. CONCLUSIONS: These results suggest that ammonia and ammonium chloride inhibit the growth of gastric cells in S phase. This mechanism may make a significant contribution to the pathogenesis of Helicobacter pylori-associated gastric mucosal atrophy.

Ammonia↗

Influence of hypoosmotic and ammonium chloride-mediated haemolysis on the integrity of human mononuclear blood cells.

Side effects of both hypoosmotic and ammonium chloride-mediated hemolysis were compared looking for cellular integrity of human peripheral blood mononuclear cells. Recovery and viability of mononuclear cells significantly declined only following water treatment. Cell loss by lysis of non-erythrocyte cells (monitored by 51Cr release) preferentially occurred in the lymphocyte population resulting in a relative enrichment of monocytes (identified by peroxidase and esterase staining as well as phagocytosis of fluorescent latex particles). Consequences of this shifted monocyte/lymphocyte ratio for immunological tests are obvious. Necessity of red cell lysis and disadvantages referred especially to NH4Cl-induced white cell functional losses are outlined.

Adolescent↗

[Effect of potassium-hydrogen interaction in the excretory mechanism of the kidneys on the acid-base and other biochemical values of the blood and urine in calves].

The effect of the competitive relationship between potassium and hydrogen in the excretory mechanism of the kidneys on metabolism was studied in calves. The intraruminal exposure of calves to 5.6 meq potassium chloride (KCl) per kg per day has, in itself, only a slight acidotic effect ascribable to a slight reduction of the excretion of acid by the kidney. The same dose of ammonium chloride (NH4Cl) has a strong acidotic effect combined with a negative influence on weight gain. Both basic types of exposure increase the concentration of inorganic phosphorus and reduce the concentration of chlorine in the blood serum. The addition of 2.8 meq of potassium chloride per kg per day to the basic dose of ammonium chloride increases metabolic acidosis, worsens the health condition (being, at times, hazardeous to life) and leads to weight losses. The same amount of ammonium chloride added to the basic dose of ammonium chloride has a relatively small acidotic action on the blood, evoking only a slight and temporary potassium retention in the serum. The negative action on the weight gains and clinical symptoms are generally weaker than in the other group. The results indicate that the acidotic environment creates in ruminants a very dangerous situation if the organism is excessively exposed to the effect of potassium at the same time.

Acid-Base Equilibrium↗

Mechanism of hypercalciuria in experimental metabolic acidosis.

To study the mechanism of hypercalciuria in metabolic acidosis, ammonium chloride loading (long) test was performed in 68 stone formers and 50 controls. Administration of ammonium chloride in both stone formers and controls produced a significant increase in urinary volume, ammonium and calcium excretions, no change in plasma calcium and creatinine clearance and significant decrease in plasma bicarbonate. However, on the third day of ammonium chloride loading test, urinary ammonium excretion and plasma bicarbonate levels were significantly lower while urinary calcium excretion was significantly greater in stone formers than in controls. Thus calciuresis could be correlated with the degree of metabolic acidosis but not with the rate of urinary ammonium excretion.

Acidosis↗

Aberrations of ammonia metabolism in ornithine carbamoyltransferase-deficient spf-ash mice and their prevention by treatment with urea cycle intermediate amino acids and an ornithine aminotransferase inactivator.

Sparse fur with abnormal skin and hair (spf-ash) mice are deficient in ornithine carbamoyltransferase (OCT) activity, but their OCT protein is kinetically normal. We administered ammonium chloride to spf-ash mice, in order to analyze ammonia metabolism and to find a rationale for the therapy of OCT deficiency. Ammonia concentration in the liver of spf-ash mice increased to a level much higher than in the control. Ammonium chloride injection caused an increase in ornithine (Orn) 5 min after injection and an increase in the sum of Orn, citrulline (Cit) and arginine (Arg) for at least 15 min in the liver of control mice, but no increase in Orn, Cit and Arg in the liver of spf-ash mice. Treatment of spf-ash mice with Arg 5-20 min prior to the injection of ammonium chloride kept the hepatic ammonia concentration at a level comparable to that without the load. A significant reciprocal relationship between ammonia and Orn concentrations in the liver of spf-ash mice 5 min after an ammonium chloride load with or without Arg strongly suggests that ammonia disposal is dependent on the supply of Orn. In spf-ash mice loaded with tryptone as a nitrogen source, Arg supplementation showed a dramatic decrease in urinary orotic acid excretion in a dose-dependent manner. Similar effects were observed with Cit and Orn at the same dose, and a long-lasting effect with an ornithine aminotransferase inactivator, 5-(fluoromethyl)ornithine, at a much lower dose. The rate of urea formation in liver perfused with ammonium chloride was lower in spf-ash mice than in controls, but with the addition of Orn to the medium it increased to a similar level in control and spf-ash mice. These results indicate that OCT is not saturated with Orn in vivo under physiological conditions and that the administration or enrichment of the urea cycle intermediate amino acids enhances the OCT reaction so that the ammonia metabolism of OCT-deficient spf-ash mice is at least partially normalized.

Amino Acid Metabolism, Inborn Errors↗

Effect of red cell lysis protocols on the expression of rat peripheral blood lymphocyte subset and activation antigens.

The effect of ammonium chloride and a commercial red cell lysing agent (Erythrolyse) on cell subset (CD4, CD8, B cell common leucocyte antigen) and activation (p55IL-2R [OX39], MHC class II) antigen expression by freshly isolated and in vitro activated rat peripheral blood lymphocytes was compared. Freshly isolated cells treated with the commercial lysing agent Erythrolyse were 42 +/- 12% p55IL-2R+, whereas p55IL-2R expression was not detected following red cell lysis with ammonium chloride. The expression of cell subset and MHC class II antigens was unaffected by either of the treatment protocols. Density gradient separation of freshly isolated cells had variable effects on antigen expression. In some cases up to a two-fold increase in p55IL-2R expression was observed, whilst in others there was a reduced receptor expression. Similarly, MHC class II antigen expression was either increased or reduced following density gradient separation. IL-2R expression on cells activated in vitro with the mitogen concanavalin A (95 +/- 2% IL-2R+) was unaffected by ammonium chloride lysis. Incubation of freshly isolated lymphocytes with p55IL-2R antibody prior to ammonium chloride treatment did not prevent the reduction in receptor expression. These findings suggest that ammonium chloride lysis of freshly isolated rat peripheral blood prior to IL-2R expression analysis should be avoided.

Ammonium Chloride↗

Elimination of clonogenic tumor cells from human bone marrow using a combination of monoclonal antibody:ricin A chain conjugates.

Effective autologous bone marrow transplantation for leukemia and lymphoma is likely to depend upon the selective removal in vitro of malignant cells from normal human bone marrow precursors. Highly specific cytotoxic conjugates formed by coupling ricin A chain to monoclonal antibodies might prove useful for the selective elimination of malignant cells. Consequently, ricin A chain conjugates have been prepared with several different murine monoclonal antibodies and tested for their ability to eliminate clonogenic Burkitt's lymphoma cells from an excess of human bone marrow. The most active reagents included an antibody:A chain conjugate which bound to the nonpolymorphic chain of the la molecule and another which reacted with the mu heavy chain of cell surface immunoglobulin. Conjugates formed with anti-common acute lymphoblastic leukemia antigen, anti-Mr 26,000 glycoprotein, and anti-B1 were much less active on these Burkitt's cells, contrasting with results of complement-dependent tumor cell lysis. Tumor cell kill was partially inhibited by the addition of greater than 2 X 10(6) human bone marrow cells/ml but could be potentiated by increasing the concentration of conjugate or by the addition of 10 mM ammonium chloride. In the presence of ammonium chloride, at least 4 logs of clonogenic tumor cells could be eliminated within 24 h from a 20-fold excess of bone marrow using 10(-7) M ricin A chain linked to one or two different antibodies. Similar treatment of normal human bone marrow temporarily inhibited granulocyte-macrophage colony-forming units (cell) formation but did not compromise establishment of continuous bone marrow cultures. The degree of selective elimination of tumor cells with A chain antibody conjugates was comparable to that achieved with 4-hydroperoxycyclophosphamide or with multiple monoclonal antibodies and complement.

Ammonium Chloride↗