SEARCH · PubMed Health

Results for “PAM”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources

PubMed2005

Synthetic- and bio-polymer use for runoff water quality management in irrigated agriculture.

Low concentrations of synthetic- or bio-polymers in irrigation water can nearly eliminate sediment, N, ortho- and total-P, DOM, pesticides, micro-organisms, and weed seed from runoff. These environmentally safe polymers are employed in various sensitive uses including food processing, animal feeds, and potable water purification. The most common synthetic polymer is anionic, high purity polyacrylamide (PAM), which typically provides 70-90% contaminant elimination. Excellent results are achieved adding only 10 ppm PAM to irrigation water, applying 1-2 kg ha(-1) per irrigation, costing 4 dollars - 12 dollars kg(-1). Biopolymers are less effective. Using twice or higher concentrations, existing biopolymers are approximately 60% effective as PAM, at 2-3 times the cost. A half million ha of US irrigated land use PAM for erosion control and runoff protection. The practice is spreading rapidly in the US and worldwide. Interest in development of biopolymer surrogates for PAM is high. If the supply of cheap natural gas (raw material for PAM synthesis) diminishes, industries may seek alternative polymers. Also "green" perceptions and preferences favor biopolymers for certain applications.

Acrylic Resins↗

PubMed1991

[The defensive role of human pulmonary alveolar macrophages and polymorphonuclear leukocytes against a strongly or weakly virulent strains of Cryptococcus neoformans].

The phagocytic and killing activities of human pulmonary alveolar macrophages (PAM) and polymorphonuclear leukocytes (PMN), and superoxide (O2-) production in phagocytizing PAM and PMN were studied by using a strongly and weakly virulent strains of Cryptococcus neoformans (C. neoformans) in mice. The strongly virulent strain was encapsulated with a thick capsule while the other had a thin one. The phagocytic and killing activities of PAM and PMN against the strongly virulent strain were lower than against the weakly virulent one. There was no significant difference between PAM and PMN in terms of phagocytic or killing activities and O2- production. It seems likely that O2- plays no defensive role in the intracellular killing of C. neoformans by PAM and PMN because no correlation was found between the killing activity and O2- production. These results indicate that human PAM and PMN play an effective role in host defense against the weakly virulent strain of C. neoformans encapsulated with a thin capsule but are not effective against the strongly virulent strain encapsulated with a thick capsule.

Adolescent↗

PubMed1991

The membrane-bound bifunctional peptidylglycine alpha-amidating monooxygenase protein. Exploration of its domain structure through limited proteolysis.

The biosynthesis of alpha-amidated peptides from their glycine-extended precursors is catalyzed by the sequential action of peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). The two enzymes are part of a bifunctional, integral membrane protein precursor, peptidylglycine alpha-amidating monooxygenase (PAM). The major forms of PAM mRNA in the adult rat atrium differ by the presence or absence of optional exon A, a 315-nucleotide segment separating the PHM and PAL domains. Using antipeptide antibodies specific to the PHM, exon A, PAL, and cytoplasmic domains of rat PAM, carbonate-washed atrial membranes were found to contain proteins corresponding to rPAM-1 and rPAM-2. Digestion of atrial membranes with a variety of endoproteinases released PHM and PAL catalytic activities. Dose-response curves indicated that both catalytic activities were extremely resistant to inactivation by trypsin. Endoproteolytic digestion of atrial membranes with trypsin, chymotrypsin, elastase, thermolysin, or endoproteinase Lys-C generated a 35-kDa PHM fragment. Digestion with trypsin, elastase, thermolysin, or endoproteinase Lys-C generated a 42-kDa PAL fragment. In contrast to the stability exhibited by the PHM and PAL domains, the cytoplasmic domain of PAM was destroyed by most of the enzymes; only digestion with endoproteinase Lys-C generated a stable fragment. Digestion with endoproteinase Arg-C removed the carboxyl-terminal tail from PAM but failed to release the PHM or PAL domains from the membranes. The PHM fragments generated by some of the endoproteinases showed a tendency to adhere to the membranes. Thus the bifunctional PAM protein consists of independent catalytic domains separated from each other and from the putative transmembrane domain by flexible regions accessible to attack by a wide variety of endoproteinases.

Amidine-Lyases↗

PubMed1991

Specificity of isozymes of murine hepatic glutathione S-transferase for the conjugation of glutathione with L-phenylalanine mustard.

Glutathione S-transferase (GST) isozymes play a central role in the protection of cells from cytotoxic chemicals and have a putative role in the intrinsic and acquired resistance of tumors to cytotoxic drugs. We have isolated and purified GST isozymes from mouse liver (M. Warholm et al., Biochemistry, 25: 4119-4125, 1986) and analyzed the metabolic products of the reaction of L-phenylalanine mustard (L-PAM) with glutathione in the presence of GST isozymes, using reverse phase high performance liquid chromatography. At pH 6.5, the spontaneous conjugation of L-PAM and glutathione is suppressed and the major product at 60 min is the monochloro, monohydroxyl derivative of L-PAM. Addition of neither class mu nor class pi isozymes to the reaction has any effect on the metabolism of L-PAM. Only isozymes of the alpha GST class catalyze the conjugation of L-PAM with glutathione. In this case, the major metabolite at 1 h is the monochloro, monoglutathionyl conjugate. Increasing the amount of mu or pi isozyme in the reaction mixture has no effect on the metabolism of L-PAM, whereas increasing the amount of alpha isozyme completely supplants hydrolysis with conjugation. Thus, increased levels of class alpha GST isozyme may represent a specific mechanism whereby cells can acquire resistance to nitrogen mustards.

Animals↗

PubMed1990

Effects of L-phenylalanine mustard and L-buthionine sulfoximine on murine and human hematopoietic progenitor cells in vitro.

The effects of L-buthionine sulfoximine (L-BSO) and L-phenylalanine mustard (L-PAM), alone and in combination, on human and murine marrow were explored using in vitro clonogenic assays to establish whether enhanced myelotoxicity might limit the clinical utility of this potent chemotherapeutic combination. One-h exposure to L-PAM produced significant concentration-dependent colony inhibition, with 70% inhibitory concentration (IC70) values ranging from 4.5 to 7.2 microM for all hematopoietic progenitors assayed. The combination of L-PAM plus 4500 microM L-BSO for 1 h did not effectively alter the IC70 values derived for L-PAM alone. In studies where marrow cells were pretreated with L-BSO for 4 h and then L-PAM for 1 additional h, the IC70 values were decreased in both murine and human marrow progenitors compared to the L-PAM control, suggesting modest potentiation of myelotoxicity. The potentiation is not so significant as to preclude human studies with this combination. One- to 5-h exposure of marrow cells from both species to 4500 microM L-BSO was only mildly myelotoxic, producing colony reductions of 22-49%. However, continuous exposure to L-BSO produced concentration-dependent colony inhibition, with IC70 values of 70, 84, and 43 microM for murine colony-forming units-granulocyte/macrophage, blast-forming units-erythroid, and colony-forming unit-erythroid, respectively.

Animals↗

PubMed1989

Lysis of antigenically unrelated tumor cells mediated by Lyt 2+ splenic T-cells from melphalan-cured MOPC-315 tumor bearers.

We have previously shown that mice cured of a large MOPC-315 tumor following low-dose melphalan (L-phenylalanine mustard, L-PAM) therapy can exert, upon challenge with MOPC-315 tumor cells, an antitumor effect against innocent bystander tumor cells present within the same tumor site (Barker, E., and Mokyr, M.B. Cancer Immunol. Immunother., 25: 215-224, 1987). Here we show that T-cells are important for the MOPC-315-induced rejection of MOPC-104E tumor cells present within the same site. To further characterize the innocent bystander killing activity exerted by L-PAM-cured MOPC-315 tumor bearers upon stimulation with MOPC-315 tumor cells, we established the in vitro conditions under which lymphoid cells from L-PAM-cured MOPC-315 tumor bearers can exert an antitumor effect against innocent bystanders. Specifically, we established that spleen cells from mice that just completed the rejection of a large MOPC-315 tumor following low-dose L-PAM therapy can, upon stimulation with MOPC-315 tumor cells, bring about the killing of antigenically unrelated tumor cells in a 12-h 51Cr release assay. The magnitude of lysis of EL4 and WEHI 22.1 tumor cells by MOPC-315 in vitro-immunized (IVI) spleen cells from L-PAM-cured MOPC-315 tumor bearers can be substantially enhanced upon reexposure of the spleen cells to MOPC-315-associated antigens during the 12-h 51Cr release assay. The lysis of innocent bystander tumor cells by these MOPC-315-IVI spleen cells was found to be mediated by T-cells of the Lyt 2 and not the L3T4 phenotype. These Lyt 2+ T-cells did not appear to mediate their lytic activity for innocent bystander tumor cells via effector macrophages, since a drastic reduction in macrophage frequency among the MOPC-315-IVI spleen cells just prior to assessing the lytic activity of the spleen cells did not reduce, but actually enhanced, the magnitude of EL4 lysis. In addition, a Lyt 2+ T-cell clone derived from mice cured of a large MOPC-315 tumor by a low dose of drug was capable, upon stimulation with MOPC-315 tumor cells, of exerting a potent lytic effect against EL4 and WEHI 22.1 tumor cells in the 12-h 51Cr release assay. Thus, Lyt 2+ T-cells independent of effector macrophages are responsible for lysis of innocent bystander tumor cells by MOPC-315-IVI spleen cells from L-PAM-cured MOPC-315 tumor bearers.

Animals↗

PubMedDate not supplied

Classification of anticancer chemotherapeutic drugs according to their immunopotentiating activity.

Both melphalan (L-PAM: L phenylalanine mustard) and 5-fluorouracil (5-FU) expressed a cytotoxic effect in vitro on MOPC-315 plasmacytoma tumour cells. However, they differed in their chemotherapeutic effectiveness in BALB/c mice bearing large MOPC-315 plasmacytoma tumours. Therapy with L-PAM, 7.5 mg/kg induced permanent regression of tumours, whereas regression induced by 5-FU, 200 mg/kg, was only transient and the mice dies finally with tumours. Moreover, spleen cells of tumour bearing mice treated with L-PAM exhibited high specific cytotoxic potential in vitro whereas spleen cells from tumour bearing 5-FU treated mice were devoid of cytotoxic potential. Effectiveness of chemotherapy with L-PAM was antagonized by treatment in combination with 5-FU. L-PAM, but not 5-FU potentiated cell mediated contact sensitivity response in vivo and impaired induction of T-suppressor cells by ConA. The parameters mentioned above indicate that L-PAM behaves as an "immunopromoting" drug and 5-FU as a "nonimmunopromoting" drug.

Adjuvants, Immunologic↗

PubMed1987

Melphalan-induced enhancement of antitumor immune reactivity in thymocytes of adult BALB/c mice bearing a large MOPC-315 tumor.

At no stage of tumor growth are thymocytes from MOPC-315 tumor bearers capable of bringing about the generation of enhanced antitumor cytotoxicity when added to immunization cultures of syngeneic normal spleen cells and "autochthonous" tumor cells. However, by Day 7 after low-dose melphalan [L-PAM (L-phenylalanine mustard)] therapy of mice bearing a large (greater than or equal to 20 mm) s.c. MOPC-315 tumor, their thymocytes exhibit such activity and it persists for at least 17 additional days. The ability of thymocytes from L-PAM-treated MOPC-315 tumor bearers to bring about the generation of enhanced antitumor cytotoxicity when added to immunization cultures of normal spleen cells and MOPC-315 tumor cells is evident over a 10-fold range of responder/stimulator cell ratios, and requires the presence of the thymocytes within the first day after initiation of the 5-day immunization cultures. In addition, immunization cultures containing normal spleen cells and thymocytes from L-PAM-treated MOPC-315 tumor bearers exhibit enhanced antitumor cytotoxicity by Day 4 after culture initiation that persists for at least 3 additional days. Thymocytes from L-PAM-treated MOPC-315 tumor bearers are able to bring about the generation of enhanced antitumor cytotoxicity only in response to stimulation with autochthonous tumor cells but not in response to stimulation with unrelated allogeneic EL4 tumor cells. The apparent specificity of the enhanced antitumor immune reactivity of thymocytes from L-PAM-treated MOPC-315 tumor bearers is not the result of extensive metastasis of tumor cells to the thymus. In fact, no tumor cells were found in the thymuses of MOPC-315 tumor bearers with methods that can detect 1 X 10(3) tumor cells, indicating that if MOPC-315 tumor cells metastasize at all into the thymus, the thymuses of mice bearing a large MOPC-315 tumor contain fewer than 1 X 10(3) tumor cells. Thus, thymocytes from mice which are engaged in the eradication of a large MOPC-315 tumor display enhanced antitumor immunity in response to stimulation with the autochthonous tumor cells. Such thymocytes may prove important to the outcome of low-dose L-PAM therapy for mice bearing a large MOPC-315 tumor, since the low-dose chemotherapy requires the contribution of T-cell-dependent antitumor immunity for its therapeutic effectiveness.

Animals↗

PubMed1986

Adjuvant therapy of breast cancer: Southwest Oncology Group studies.

The Southwest Oncology Group has conducted a series of randomized studies of adjuvant therapy in patients with primary breast cancer and positive axillary nodes. The first study, during which combined chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) administered for 1 year was compared with single agent therapy with melphalan (L-PAM) for 2 years, was activated in 1975 and closed in 1978. Of the 366 patients who were eligible, 191 received L-PAM and 175 were given CMFVP. The 2 groups were comparable with regard to known prognostic factors. At a median follow-up of 8 years, CMFVP continues to be superior to L-PAM in disease-free (P = .005) and overall survival (P = .01). Thirty-five percent of patients on CMFVP have died compared with 46% on L-PAM. The greatest survival benefit is apparent in premenopausal women and women with 4 or more positive axillary nodes. Acute toxicity was more frequent with CMFVP than with L-PAM, but it was acceptable and reversible with both regimens. Long-term toxicity was limited to myeloproliferative disease in 2 patients on L-PAM and 1 on CMFVP. The second-generation series of studies, activated in 1979, were designed according to nodal status, estrogen receptor (ER) status, and menopausal status. We randomized ER-negative, node-negative patients to 6 months of combination chemotherapy or to no treatment. Because of slow accrual, the study was closed and patients are now being entered onto a similar intergroup study with the Eastern Cooperative Oncology Group. We randomized ER-negative, node-positive patients to either 1 or 2 years of CMFVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Effect of in vitro inoculation of bovine respiratory syncytial virus on bovine pulmonary alveolar macrophage function.

Viruses may predispose the respiratory tract to the development of secondary bacterial pneumonia by impairing functions of alveolar macrophages. The effects of bovine respiratory syncytial virus (BRSV) on selected functions of bovine pulmonary alveolar macrophages (PAM) were examined in vitro. Alveolar macrophages were obtained from nonsedated cattle, using a polypropylene tube passed intranasally into the lung. The PAM lavaged from the lung were allowed to adhere to glass coverslips or plastic tissue culture plates, and were exposed to BRSV for 2 hours. Control and BRSV-inoculated PAM were compared at intervals over a 72-hour period for their abilities to phagocytize and kill Staphylococcus epidermidis, rosette with and phagocytize antibody-coated sheep RBC (SRBC), phagocytize latex particles, and influence lysosomal enzyme activity. Challenge exposure with BRSV did not affect the ability of PAM to adhere and did not affect cell viability. There were numerical differences between control and BRSV-inoculated cell populations in phagocytosis and killing of S epidermidis, but these were not significant (P greater than 0.05). There was less than 5% difference in the abilities of control and BRSV-challenged PAM to phagocytize latex beads. When Fc-receptor-mediated phagocytosis of antibody-coated SRBC was compared with controls, BRSV-challenged PAM had significantly (P less than 0.05) impaired phagocytic function, which was maximal 72 hours after BRSV inoculation; the phagocytic impairment occurred in spite of normal Fc-receptor function, as determined by rosetting with antibody-coated SRBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

PubMed1985

Biologic effects of prolonged melphalan treatment of murine long-term bone marrow cultures and interleukin 3-dependent hematopoietic progenitor cell lines.

The mechanism of alkylating agent-induced leukemia is unknown. For the determination of whether chronic alkylating agent treatment of hematopoietic stem cells in vitro was detectably leukemogenic, murine long-term bone marrow cultures (LTBMC) and clonal interleukin 3 (IL-3)-dependent multipotential hematopoietic progenitor cell lines [B6SUtA clone (cl) 27 and Ro cl 3-1] derived from LTBMC were chronically pulse treated in vitro with the alkylating agent melphalan [L-phenylalanine mustard (L-PAM)]. Weekly treatment of C3H/HeJ or CD-1 Swiss mouse LTBMC with 3 X 10(-6)M L-PAM significantly decreased cumulative production of nonadherent granulocytes and granulocyte-macrophage progenitor cells responsive to L-cell or WEH1-3 cell colony-stimulating factor compared to the production seen in untreated control cultures; it also significantly reduced the hematopoietic longevity (13 wk compared to greater than 20 wk for untreated control cultures). Weekly, twice weekly, or daily (3 X 10(-6)M) L-PAM treatment of IL-3-dependent cell lines induced gradual L-PAM adaptation in the absence of a detectable change in the maximum binding capacity of 125I-labeled IL-3. No leukemogenic variants of line B6SUtA cl 27 were detectably induced. However, 3 stably expressed marker chromosomes were induced after 12 months of L-PAM treatment of line B6SUtA cl 27. Thus IL-3-dependent hematopoietic progenitor cells slowly adapt to L-PAM when in suspension culture in vitro. Physiologic expression of drug toxicity in LTBMC may prevent this hematopoietic cell gradual adaptation.

Animals↗

PubMed1979

Hypersensitivity reactions to iv melphalan during treatment of multiple myeloma: Cancer and Leukemia Group B experience.

Ten patients developed allergic reactions to iv melphalan (L-PAM) during therapy for multiple myeloma. The incidence of such reactions was 2.4% among 425 patients receiving iv L-PAM with or without other drugs and 3.9% among 255 patients receiving iv L-PAM alone. Only one such reaction was demonstrated in 294 patients who initially received oral L-PAM. The median day of first reaction to iv L-PAM was Day 222 (range, Days 44-909) and the median total dose prior to a reaction was 185 mg (range, 51-250 mg). Of five patients who subsequently received oral L-PAM, four developed a reaction similar to that experienced with the iv drug.

Administration, Oral↗

PubMed1978

Pulmonary alveolar macrophage response to hyperbaric carbon monoxide exposure.

The sublethal effects of carbon monoxide (CO) in hyperbaric environments have not been adequately characterized. A physiologically sensitive indicator of sublethal effects of a contaminant is the pulmonary alveolar macrophage (PAM). The guinea pig PAM and its reaction to various CO concentrations at 8 atmospheres absolute (ATA) and the surface-equivalent concentrations at 1 ATA were studied in this experiment. In the absence of CO, PAM counts and viabilites from guinea pigs exposed to a helium-oxygen environment at either 1 or 8 ATA were not significantly different from one another. Mean PAM viability for guinea pigs exposed to CO concentrations at 2250--4200 mg/m3 at 8 ATA was 68.4 +/- 7.3% and was not significantly different from the 1-ATA viability value of 72.0 +/- 4.5% for the 1600--4200 mg/m3 CO range. The data show that at 1 to 8 ATA and CO concentrations of 1600--4200 mg/m3, the decrease in PAM viability was accompanied by dramatic five- to sixfold increases in PAM counts.

Animals↗

PubMed1983

Language development in a group of very low-birth-weight children whose postauricular myogenic response was tested in infancy.

A new instrument for the detection of the postauricular myogenic (PAM) response was used to test the hearing of 106 infants weighing less than or equal to 1,500 g when they were aged 1 to 21 months. Eighty-eight infants showed a positive response at 60 dB hearing level (HL) (normal). The other 18 did not respond; four were found to have sensory neural hearing loss and another six had conductive loss due to secretory otitis media. Of the 106 children, 90 aged 2 years or more (mean 27 months) were living in the United Kingdom, and their language development was assessed. It was normal in 67/75 children whose PAM response had been normal in infancy. The remaining eight children with normal PAM responses in infancy, had language delay. All eight children had problems that were thought to account for the delay, including three with mental retardation, three with cerebral palsy, and two whose families did not speak English. Language development was normal in 11/15 children tested whose PAM responses had been found to be abnormal, including all six whose secretory otitis media had been diagnosed and treated at the time of the PAM test. Delay in language development was found in 3/4 children with sensory neural hearing loss who were available for testing and in one child with overall developmental delay. It is concluded that a positive PAM response at 60 dB HL in infancy indicated hearing adequate for the development of normal speech in otherwise normal children among a group of infants at high risk of hearing loss.

Child, Preschool↗

PubMed1977

Lymphoproliferative responses to antigens mediated by human pulmonary alveolar macrophages.

We evaluated the ability of human pulmonary alveolar macrophages (PAMs) to mediate (3H)-thymidine incorporation by blood lymphocytes severely depleted of monocytes when stimulated with soluble microbial and allogeneic lymphocyte antigens. Low (less than 2%) concentrations of PAM's from nonsmokers or blood monocytes did not support optimal responses. Over all, at greater than or equal to 10% concentrations, PAM's from nonsmokers supported higher responses than monocytes. At less than or equal to 10% concentrations, PAM's from heavy cigarette smokers mediated significantly less incorporation than did similar concentrations of PAM's from nonsmokers (p less than 0.05). The findings indicate that PAM's from healthy nonsmokers are functionally competent macrophages in terms of mediating lymphoproliferation in cultures stimulated with antigens. This classical macrophage function is impaired with cigarette smoking.

Adult↗

PubMed1997

Neuropeptide amidation in Drosophila: separate genes encode the two enzymes catalyzing amidation.

In vertebrates, the two-step peptide alpha-amidation reaction is catalyzed sequentially by two enzymatic activities contained within one bifunctional enzyme called PAM (peptidylglycine alpha-amidating mono-oxygenase). Drosophila head extracts contained both of these PAM-related enzyme activities: a mono-oxygenase (PHM) and a lyase (PAL). However, no bifunctional PAM protein was detected. We identified cDNAs encoding an active mono-oxygenase that is highly homologous to mammalian PHM. PHM-like immunoreactivity was found within diverse larval tissues, including the CNS, endocrine glands, and gut epithelium. Northern and Western blot analyses demonstrate RNA and protein species corresponding to the cloned PHM, but not to a bifunctional PAM, leading us to predict the existence of separate PHM and PAL genes in Drosophila. The Drosophila PHM gene displays an organization of exons that is highly similar to the PHM-encoding portion of the rat PAM gene. Genetic analysis was consistent with the prediction of separate PHM and PAL gene functions in Drosophila: a P element insertion line containing a transposon within the PHM transcription unit displayed strikingly lower PHM enzyme levels, whereas PAL levels were increased slightly. The lethal phenotype displayed by the dPHM P element insertion indicates a widespread essential function. Reversion analysis indicated that the lethality associated with the insertion chromosome likely is attributable to the P element insertion. These combined data indicate a fundamental evolutionary divergence in the genes coding for critical neurotransmitter biosynthetic enzymes: in Drosophila, the two enzyme activities of PAM are encoded by separate genes.

Amides↗

PubMed1977

Acid-base status in dietary treatment of phenylketonuria.

Blood acid-base status, serum electrolytes, and urine pH were examined in 64 infants and children with phenylketonuria (PKU) treated with three different low phenylalanine protein hydrolyzates (Aponti, Cymogran, AlbumaidXP) and two synthetic amino acid mixtures (Aminogran, PAM). The formulas caused significant differences in acid-base status, serum potassium, and chloride, and in urine pH. In acid-base balance studies in two patients with PKU, Aponti, PAM, and two modifications of PAM (P2 + P3) were given. We observed a change from mild alkalosis to increasing metabolic acidosis from Aponti (serum bicarbonate 25,8 mval/liter) to P3 (24,0Y, P2 (19, 3) and PAM (17,0). Urine pH decreased and renal net acid excretion increased. In the formulas PAM, P2 and P3 differences in renal net acid excretion correlated with differences in chloride and sulfur contents of the diets and of the urines. New modifications of AlbumaidXP and of PAM, prepared according to our recommendations, showed normal renal net acid excretion (1 mEq/kg/24 hr) in a balance study performed in one patient with PKU and normal acid base status in 20 further patients.

Acid-Base Equilibrium↗

PubMed1998

Importance of the B7-2 molecule for low dose melphalan-induced acquisition of tumor-eradicating immunity by mice bearing a large MOPC-315 tumor.

We have previously shown that low dose melphalan (L-phenylalanine mustard; L-PAM) therapy of hitherto immunosuppressed mice bearing a large (20-mm) s.c. MOPC-315 tumor leads to the acquisition of potent CD8+ T cell-mediated antitumor immunity which in turn eradicates the large tumor burden not eradicated by the direct antitumor effects of the drug. Here we show the preferential importance of the B7-2 costimulatory molecule for the curative effectiveness of low dose L-PAM for mice bearing a large MOPC-315 tumor by demonstrating that treatment with anti-B7-2 mAb, but not anti-B7-1 mAb, reduced the percentage of mice cured by the low dose L-PAM. In addition, we show the preferential importance of the B7-2 molecule for the low dose L-PAM-induced acquisition of the ability of tumor-infiltrating lymphocytes from MOPC-315 tumor bearers to secrete IL-2 and IFN-gamma as well as to exert an anti-MOPC-315 CTL effect. The preferential importance of the B7-2 molecule may be due to the higher level of B7-2 than of B7-1 expression on B220+ cells and on tumor cells from the s.c. tumor nodule of low dose L-PAM-treated MOPC-315 tumor bearers and the selective up-regulation of the B7-2 molecule in the draining of these mice. Thus, the B7-2 molecule plays a dominant role in the acquisition of T cell-dependent tumor-eradicating immunity in low dose L-PAM-treated mice bearing a large MOPC-315 tumor, suggesting that one of the mechanisms by which chemotherapy may enhance antitumor immunity is through up-regulation of critical costimulatory molecules that enhance antitumor responses.

Animals↗