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PubMed1993

Pulmonary alveolar macrophages in molecular epidemiology and chemoprevention of cancer.

In addition to possessing an extraordinary sweeping activity, pulmonary alveolar macrophages (PAM) are equipped with the biochemical mechanisms involved in the metabolism of carcinogens, which were found to be inducible in humans by cigarette smoke. Moreover, several defense processes were stimulated in rat PAM after in vivo administration of the anticarcinogen N-acetylcysteine (NAC). Benzo[a]pyrene diol epoxide (BPDE)-DNA adducts, as revealed by synchronous fluorescence spectrophotometry, were selectively detected in PAM of smokers and persisted up to 6 months. The amount of adducts was significantly correlated with the number of currently smoked cigarettes but not with the cigarettes smoked in a lifetime (pack-years). Nevertheless, deviations from the regression line pointed out the role of interindividual variability factors in adduct formation. Probably due to the low mitotic rate of PAM in the respiratory lumen, the frequency of micronuclei was not enhanced in smokers. However, parallel assays in rats showed that micronuclei can be enhanced after massive intratracheal administration of benzo[a]pyrene or whole-body exposure to high amounts of mainstream cigarette smoke, which also induced BPDE-DNA adducts in lung cells and other organs, including the heart. All these adverse effects were markedly inhibited by the oral administration of NAC, which provides the premise and rationale for a future study on the protective effects of oral NAC in heavy smokers.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2001

Staining pattern of the brush border and detection of cytoplasmic granules in the uriniferous tubules of female DBA/2Cr mouse kidney: comparison among various fixations and stains.

The proximal straight tubules of the female mouse kidney exhibit heavy periodic acid Schiff (PAS) staining in their brush borders and numerous cytoplasmic granules. In the present study, the female DBA/2Cr mouse kidney was examined, using various fixatives (formalin, PFA, PLP, Zamboni's, Bouin, or Carnoy solution) and various staining methods (HE, PAS, alcian blue, periodic acid methenamine-silver (PAM), toluidine blue, azan, or Congo red). Under azan and PAM, the staining pattern of the brush border was similar to that of PAS, and few effects of the fixative were observed. Cytoplasmic granules were clearly detected with PAM as well as PAS. However, these granules were not detected with Carnoy solution. Furthermore, distribution of granules differed between PAS and PAM.

Animals↗

PubMed1991

[Perceptions of the head physician concerning educational activities in Municipal Health Services].

The results of a research project carried out along with head-physicians of the Municipal Health Services (PAMs) of the city of S. Paulo in order to survey their knowledge, expectations and willingness to participate in and incentivate educational programs in the various PAMs, are reported on. An open-ended questionnaire was answered by 88.6% of the head-physicians. Results showed that the concept of health of the majority of the PAMs' head-physicians (66.3%) was coincidental with that adopted by the WHO. Only 2.9% considered that health is related to quality of life. Health education was seen as the provision of information by 70.0%; only 6.7% recognized their responsibility for the process of social and health change. According to 68.2% of them, health actions were acknowledged to be useful tools for making the users aware of the importance of having the diseases treated. Health actions, their planning, implementation and evaluation were considered to be the responsibility of all who work at the PAMs, but mainly of nurses, social workers and the health educator. Some difficulties in implementing educational activities were indicated; among them being lack of sufficient material and adequate space for their implementation, lack of professional Public Health Educators and, mainly, a lack of motivation on the part of both staff and population. The majority of the head-physicians recognized that educational activities are important, that they are carried out at least by part of their staffs, although frequently hampered by technical and operational difficulties.

Attitude of Health Personnel↗

PubMed1993

The effect of acupuncture stimulation of the middle latency auditory evoked potential.

The effects of acupuncture stimulation (AS) on the middle latency auditory evoked potentials (MLAEPs) were studied in 19 normal male volunteers. Scalp recordings were made from 21 points (including Cz) and posterior auricular muscle (PAM) electrodes referenced to the linked mastoid. Four components of MLAEPs (Po, Na, Pa and Nb) and two components of PAM reflex (N12 and P17) were statistically analyzed for changes in latency and amplitude. Wave phase of Po and Na reversed to N12 and P17, respectively, and the peak-to-peak amplitude of Po-Na, Na-Pa, Pa-Nb and N12-P17 showed a marked increase during AS to the ipsilateral side whereas no change in latency was detected. Each component's isovoltage topographic maps and dipole locations were calculated to be near both PAM (Po and Na) and temporal positions (Pa and Nb) during AS. These data showed that AS can promote MLAEPs activity and these signals (Po and Na) may originate from increased activity in N12 and P17 of the PAM reflex, respectively, and that the auditory cortex of the temporal gyrus is the generator substrate of Pa and Nb.

Acoustic Stimulation↗

PubMed2003

Activities of therapeutic agents against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis.

Inhalation of water contaminated with Naegleria fowleri may lead to a potentially fatal infection of the central nervous system known as primary amebic meningoencephalitis (PAM). Amphotericin B (AMB), an antifungal drug, is the only agent with established clinical efficacy in the treatment of PAM, though therapy with this drug is not always effective and has been associated with adverse effects on the kidneys and other organs. We investigated the activity of various therapeutic agents against N. fowleri in an attempt to identify other useful agents for treating PAM. Several of these agents exhibited in vitro activity against the Lee (M67) strain of N. fowleri. The minimum inhibitory concentrations of these agents were 0.1 microg/ml (ketoconazole), 1 microg/ml (liposomal AMB), and 10 microg/ml (minocycline, quinupristin-dalfopristin, and trifluoperazine). Other agents had a minimum inhibitory concentration > 10 microg/ml (linezolid) or > 100 microg/ml (rifampin). In a mouse model of PAM, none of the untreated control mice survived, whereas the survival of treated animals was 50% (quinupristin-dalfopristin), 30% (ketoconazole and liposomal AMB), 20% (trifluoperazine), and 10% (linezolid and minocycline). Further studies are needed to ascertain whether these agents have synergistic activity with AMB in vitro and in vivo.

Acetamides↗

PubMed2001

Effects of Anabaena spiroides (Cyanobacteria) aqueous extracts on the acetylcholinesterase activity of aquatic species.

The effects of aqueous extracts from a cyanobacteria species, Anabaena spiroides, on fish (Odontesthes argentinensis), crab (Callinectes sapidus), and purified eel acetylcholinesterase (AChE) activity were studied. In vitro concentrations of A. spiroides aqueous extract that inhibited 50% of enzyme activity (IC50) were 23.0, 17.2, and 45.0 mg/L of lyophilized cyanobacteria for eel, fish, and crab AChE, respectively. Eel AChE inhibition follows pseudo-first-order kinetics, the same expected for organophosphorus pesticides. Inhibition of purified eel AChE using mixtures of bioxidized malathion and aqueous extract of A. spiroides showed a competitive feature (p < 0.05), suggesting that the toxin(s) could be structurally similar to an organophosphorus pesticide and that toxins present in the aqueous extract inhibit the active site of the enzyme. The inhibition recovery assays using 2-PAM (0.3 mM) showed that (1) bioxidized malathion inhibited 27.0 +/- 1.1% of crab and 36.5 +/- 0.1% of eel AChE activities; (2) with bioxidized malathion + 2-PAM the registered inhibition was 13.2 +/- 2.1% and 3.7 +/- 0.5% in crab and eel AChE, respectively; (3) the aqueous extract from A. spiroides inhibited 17.4 +/- 2.2% and 59.9 +/- 0.5% of crab and eel AChE activity, respectively; and (4) aqueous extract + 2-PAM inhibited 22.3 +/- 2.6 and 61.5 +/- 0.2% of crab and eel AChEs. The absence of enzyme activity recovery after 2-PAM exposure could imply that the enzyme aging process was extremely quick.

Acetylcholinesterase↗

PubMedDate not supplied

Enhanced biological phosphorus removal from wastewater by biomass with different phosphorus contents, Part I: Experimental results and comparison with metabolic models.

Enhanced biological phosphorus removal (EBPR) in waste-water treatment involves at least two types of bacterial metabolism: a polyphosphate-accumulating metabolism (PAM) and a glycogen-accumulating metabolism (GAM). Laboratory-scale sequencing batch reactors operated in an anaerobic-aerobic cycle confirmed that low influent phosphorus/chemical oxygen demand (COD) ratio feed favored a GAM-dominated culture and high influent phosphorus/COD ratio feed favored a PAM-dominated culture, as indicated by changes in phosphorus, acetate, glycogen, and polyhydroxyalkanoate (PHA) concentrations during the anaerobic phase. Differential PAM and GAM dominance may explain variance in anaerobic phosphorus release, glycogen degradation, and PHA synthesis per acetate uptake ratios previously reported in EBPR systems and proposed metabolic models. The measurement of the ratios of anaerobic phosphorus release to acetate uptake and glycogen degradation to acetate uptake is suggested as an assay to estimate the relative dominance of PAM and GAM, respectively, in EBPR cultures.

Acetates↗

PubMed2001

Effects of training on resting peripheral blood and BAL-derived leucocyte function in horses.

In this study, the effects of prolonged, high intensity training on aspects of peripheral blood and bronchoalveolar lavage (BAL)-derived leucocyte function were evaluated in 8 horses. All horses undertook a 7 week endurance training programme, followed by 5 weeks of high intensity training (HIT). Thereafter, horses were divided into control (C) and overtraining (OT) groups. The frequency and intensity of training were increased more substantially for horses in the OT group. Training was terminated in week 32 when horses in the OT group demonstrated a significant performance reduction. Peripheral blood and BAL samples were collected from 4 horses in C and OT groups in training weeks 7, 11, 14, 18, 22, 28 and 32. Flow cytometric techniques were used to assess phagocytosis by peripheral blood neutrophils and pulmonary alveolar macrophages (PAM), and oxidative burst activity of neutrophils, PAM, peripheral blood and BAL-derived lymphocytes. Peripheral blood neutrophil phagocytosis (internalisation) increased during the initial HIT period and decreased from week 16 when the training workload was increased for both groups. The oxidative burst activity of peripheral blood neutrophils and lymphocytes similarly increased and then decreased in response to training. The oxidative burst activity of PAM was reduced towards the end of the overtraining phase of the programme. Pulmonary alveolar macrophage phagocytosis and oxidative burst activity of BAL-derived lymphocytes demonstrated no change throughout the course of the study. There was no difference in results obtained from C or OT group horses, suggesting that protracted HIT, rather than overtraining, was associated with impaired cell function. The detrimental effects observed in peripheral blood neitrophil and PAM function may indicate impaired nonspecific immunity which may adversely affect the health and performance of horses undergoing protracted periods of intense training.

Animals↗

PubMedDate not supplied

Neutrophil involvement in the retention and clearance of dust intratracheally instilled into the lungs of F344/N rats.

This study evaluated polymorphonuclear leukocyte (PMN) involvement in translocation of dust to bronchial lymph nodes after deposition of dust in the lungs of control and neutropenic F344/N rats. Rats were rendered neutropenic with an intraperitoneal (IP) injection of anti-rat PMN antiserum (APA); control rats were injected IP with 0.9% saline solution. Eighteen hours after IP injections, control and APA-treated rats were instilled intratracheally with 5 x 10(8) microspheres suspended in 0.9% saline solution, which caused an influx of PMNs into the pulmonary airspaces of control rats, but not of APA-treated rats. One day postinstillation (PI), 77.2% of the microspheres recovered in bronchoalveolar lavage fluid (BALF) from control rats were associated with pulmonary alveolar macrophages (PAMs) and 18.8% with PMNs; 4.0% were free. In BALF from the APA-treated rats, 66.3% of the microspheres were associated with PAMs and 0.3% with PMNs; 36.3% were free. Two days PI, about 95% of the microspheres in BALF from control and APA-treated rats were associated with PAMs; by 4 and 7 days PI, essentially 100% were with PAMs. Amounts of microspheres translocated to bronchial lymph nodes of control rats were four fold less than in the APA-treated rats on days 2, 4, and 7 PI (p < .05). The results suggest that PMNs in pulmonary airspaces of F344/N rats phagocytize dust and thereby interfere with the mechanism(s) involved in dust penetration into the pulmonary interstitium.

Animals↗

PubMed1997

A pilot study of the theoretical and technical competence and appropriate education for the use of nine physical agent modalities in occupational therapy practice.

OBJECTIVE: This study described occupational therapy practitioners' perceptions about the content and method of training or education necessary for gaining theoretical and technical competence in the use of nine physical agent modalities (PAMs). METHOD: A survey was developed and sent to 543 members of the Physical Disabilities Special Interest Section of the American Occupational Therapy Association who had identified their primary area of practice as hand therapy. One hundred and fifty-one completed surveys (28% response rate) were returned. RESULTS: The respondents indicated that theoretical and technical expertise necessary for competent use of PAMs varied according to the type of modality being considered. Continuing education courses were identified as the best method for gaining theoretical and technical competence for the use of deep thermal agents, such as ultrasound and electrical stimulation agents, whereas entry-level professional education and one-the-job training were identified as most appropriate for superficial thermal agents, such as paraffin bath and hot and cold packs. CONCLUSION: The results suggest that considerations regarding the type and amount of education necessary for gaining theoretical and technical competence in the use of PAMs depend on the type of modality being addressed. These differences should be considered in the future development of competency objectives for the use of PAMs.

Adult↗

PubMed1999

High-resolution computed tomography of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease. It has been reported predominantly in Turkey. We report a case of PAM with characteristic high-resolution computed tomography (CT) findings. A 45-year-old Taiwanese woman had progressive difficulty in breathing for 7 years. Her chest radiographs showed diffuse high-density micronodules and reticular lines that obliterated the bronchovascular bundles and the margin of the heart and diaphragm. The micronodules were scattered throughout both lung fields with basal predominance. Examination of a transbronchial lung biopsy specimen showed PAM. High-resolution CT showed a unique and characteristic calcified reticular pattern and thickening of the interlobular septa of the lung parenchyma, with predominant basal and peripheral lung distribution. Reticulonodular changes of the interlobular septa and intralobular interstitial lines associated with subpleural air cysts and paraseptal emphysema were evident. These high-resolution CT findings are pathognomonic for PAM. Thus, lung biopsy may be avoided in the presence of this characteristic finding.

Calcinosis↗

PubMed1999

Norepinephrine-mediated inhibition of antitumor cytotoxic T lymphocyte generation involves a beta-adrenergic receptor mechanism and decreased TNF-alpha gene expression.

We have previously shown that norepinephrine (NE) inhibits the in vitro generation of anti-MOPC-315 CTL activity by spleen cells from BALB/c mice rejecting a large MOPC-315 tumor as a consequence of low-dose melphalan (l -phenylalanine mustard (l -PAM)) treatment (l -PAM TuB spleen cells). Since TNF-alpha plays a key role in the generation of antitumor CTL activity in this system, we determined whether NE mediates this inhibition through inhibition of TNF-alpha production. Here, we show that NE inhibits the production of TNF-alpha protein and mRNA by l -PAM TuB spleen cells stimulated in vitro with mitomycin C-treated tumor cells. Flow cytometric analysis of intracellular expression of TNF-alpha revealed substantial NE-mediated decreases in the percentages of TNF-alpha+ cells among CD4+ and CD8+ T cells and F4/80+ activated macrophages. NE inhibition of CTL generation was largely overcome by addition of TNF-alpha to the stimulation cultures. When the beta-adrenergic antagonist propranolol was added to the stimulation cultures of l -PAM TuB spleen cells at a concentration that prevented NE-induced cAMP elevation, the NE-mediated decrease in TNF-alpha mRNA and NE-mediated inhibition of CTL generation were reversed. Collectively, these results suggest that NE inhibits antitumor CTL generation, at least in part, by inhibiting TNF-alpha synthesis through a mechanism(s) involving beta-adrenergic receptor signaling.

Animals↗

PubMed2001

Expression of adrenomedullin and peptide amidation activity in human prostate cancer and in human prostate cancer cell lines.

After therapeutic hormone deprivation, prostate cancer (CaP) cells often develop androgen-independent growth through not-well-defined mechanisms. The presence of neuroendocrine (NE) cells is often greater in prostate carcinoma than in normal prostate, and the frequency of NE cells correlates with tumor malignancy, loss of androgen sensitivity, increase of autocrine-paracrine activity, and poor prognosis. In some CaPs, neuropeptides have been previously implicated as growth factors. Peptidylglycine alpha-amidating monooxygenase (PAM) is the enzyme producing alpha-amidated bioactive peptides from their inactive glycine-extended precursors. In the present work, we demonstrate that androgen-independent PC-3 and DU145 cell lines, derived from human CaP, express PAM in vitro and in xenografts implanted in athymic nude mice, indicating that they are able to produce alpha-amidated peptides. Contrarily, barely detectable levels of PAM were found in the androgen-sensitive LNCaP cell line. We also show that whereas PC-3 and DU145 cells produce and secrete adrenomedullin (AM), a multifunctional amidated peptide, no expression was found in LNCaP cells. We further demonstrate that AM acts as a growth factor for DU145 cells, which suggests the existence of an autocrine loop mechanism that could potentially drive neoplastic growth. PAM mRNA levels were found to be 3-fold higher in prostate adenocarcinomas compared with that of human benign prostate hyperplasia (BPH) as demonstrated by real-time quantitative reverse transcription-PCR. The analysis of AM message expression in BPH and CaP (Gleason's score, 6-9) shows a clear distinction between benign and CaP. The expression was detected only in adenocarcinomas tissues with a marked increase in samples with a high Gleason's score. Immunocytochemically, AM was localized in the carcinomatous epithelial compartment. NE phenotype, assessed after the immunocytochemical localization of neuron-specific enolase (NSE), was found in both the epithelial and the stromal compartments of cancers; in BPH, only some spare basal cells were NSE-labeled. Cancer progression could be accelerated by peptides secreted by a population of cells capable of inducing androgen-independent tumoral growth via autocrine-paracrine mechanisms.

Adenocarcinoma↗

PubMed2001

Loss of p53 function confers high-level multidrug resistance in neuroblastoma cell lines.

Neuroblastomas can acquire a sustained high-level drug resistance during chemotherapy and especially myeloablative chemoradiotherapy. p53 mutations are rare in primary neuroblastomas, but a loss of p53 function could play a role in multidrug resistance. We determined p53 function by measuring induction of p21 and/or MDM2 proteins in response to melphalan (L-PAM) in seven L-PAM-sensitive and 11 L-PAM-resistant neuroblastoma cell lines. p53 was functional in seven/seven drug-sensitive but in only 4/11 drug-resistant cell lines (P = 0.01). In four of the seven cell lines lacking p53 function, mutations of p53 were detected by the microarray GeneChip p53 Assay and automated sequencing, whereas six cell lines with functional p53 had no evidence of p53 mutations. All of the cell lines with wild-type (wt) p53 showed a strong transactivation of the p53-HBS/CAT reporter gene, whereas the four cell lines with mutant p53 failed to transactivate p53 HBS/CAT. Overexpression of MDM2 protein (relative to p53 functional lines) was seen in two p53-nonfunctional cell lines with wt p53; one showed genomic amplification of MDM2. Nonfunctional and mutated p53 was detected in a resistant cell line, whereas a sensitive cell line derived from the same patient before treatment had functional and wt p53. Loss of p53 function was selectively achieved by transduction of human papillomavirus 16 E6 (which degrades p53) into two drug-sensitive neuroblastoma cell lines with intact p53, causing high-level drug resistance to L-PAM, carboplatin, and etoposide. These data obtained with neuroblastoma cell lines suggest that the high-level drug resistance observed in some recurrent neuroblastomas is attributable to p53 mutations and/or a loss of p53 function acquired during chemotherapy. If confirmed in patient tumor samples, these data support development of p53-independent therapies for consolidation and/or salvage of recurrent neuroblastomas.

Antineoplastic Agents↗

PubMed2003

Evaluating reptile exposure to cholinesterase-inhibiting agrochemicals by serum butyrylcholinesterase activity.

Blood samples from lizards (Gallotia galloti) collected from two agricultural areas (Las Galletas and Punta del Hidalgo) and two reference areas on the Island of Tenerife (Canary Islands, Spain) were analyzed for butyrylcholinesterase (BChE) activity. Serum BChE activity was characterized first by in vitro experiments using selective substrates and inhibitors. Of the total cholinesterase (ChE) activity, 74% could be attributed to BChE activity. This portion of the total ChE activity was inhibited dose dependently by tetraisopropyl pyrophosphoramide and hydrolyzed the substrate butyrylthiocholine iodide. No enzyme inhibition was observed at high substrate concentration. Twenty-one lizards collected from agricultural sampling sites showed significant inhibition (p < 0.001) of BChE activity (mean +/- standard deviation [SD] of 4.66 +/- 2.63 micromol/min/ml for lizards from Las Galletas and 5.13 +/- 1.48 for lizards from Punta del Hidalgo) compared with BChE activity for lizards from the reference sites (6.35 +/- 1.75 micromol/min/ ml). Las Galletas had the highest number of lizards (22%) with significantly inhibited BChE activity. In vitro assays showed that 10(-4) M pyridine-2-aldoxime methochloride (2-PAM) reactivated dichlorvos- or paraoxon-inhibited BChE activity within a 60-min incubation period. Almost all serum samples with depressed BChE activity that were collected from lizards from agricultural areas responded to 2-PAM reactivation of enzyme activity (8-60% increase in enzyme activity). Reactivation by treatment with 2-PAM confirmed that the depression of BChE activity was attributable to organophosphorus (OP) compounds. Evaluation of BChE activity levels and the chemical reactivation of serum BChE activity in G. galloti using 2-PAM was found to be a sensitive indicator of G. galloti exposure to OP compounds.

Animals↗

PubMed1954

Treatment of early infectious syphilis with N,N'-dibenzylethylenediamine dipenicillin G; a second report.

A new penicillin salt-N,N'-dibenzylethylenediamine dipenicillin G (Bicillin)(a)-was given, in single injections of 2,500,000 units, to 196 patients with early infectious syphilis. The seronegativity rates after three months were 65% for primary syphilis cases and 25% for secondary syphilis patients; after six months, the rates were 80% and 60%, respectively. At the end of the 21-month observation period, satisfactory results were recorded in 96.6%-100.0% of the primary syphilis patients, and in 92%-95% of those treated for secondary syphilis. The respective cumulative re-treatment rates were 3.4% and 4.1%.The results of the secondary syphilis treatment were then compared with those obtained with single-injection schedules of 2,400,000 and 4,800,000 units of procaine penicillin G in oil with 2% aluminium monostearate (PAM). The cumulative re-treatment rates 21 months after treatment were: Bicillin, 4.1%; PAM (2.4 million units), 14.2%; and PAM (4.8 million units), 5.1%. It would thus appear that a single injection of 2,500,000 units of Bicillin is as effective as one of 4,800,000 units of PAM.

Communicable Diseases↗

PubMed2003

Improvement of automatic in-gel digestion by in situ alkylation of proteins.

We have recently improved the automation of an in-gel digestion system, DigestPro 96, using in situ alkylation of proteins with acrylamide, conducted during one-dimensional (ID) SDS-PAGE. The improved method included the processes of destaining, dehydration, trypsin digestion, and extraction but excluded the reduction and alkylation steps following staining of proteins with CBB. The extracted peptide mixtures were directly loaded onto a micro C18 LC column of the mass spectrometer. The resultant spectra were processed with "Mascot" search engine to estimate the sequence coverage of the bovine serum albumin (BSA). The original method, designed for Laemmli ID SDS gel applications, consisted of reduction and post-alkylation with iodoacetamide, which produced carboxyamidemethyl (CAM; -S-CH2CONH2) derivatives. The original method also included a desalting step essential for mass spectrometry, especially matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We compared the original and improved methods using BSA (3 pmol loaded to the gel, one third of digested peptide mixture injected into LC-MS). The original method yielded both CAM and propionicamide (PAM;-S-CH2CH2CONH2) derivatives. The source of PAM derivatives is the unpolymerized acrylamide formed during electrophoresis. The sequence coverage of CAM derivatives of BSA by the original method was 10% with desalting and 19% without desalting. The sequence coverage of PAM derivative by the improved method was 32%. Our results clearly show the advantage of our improved automated in-gel digestion method for in situ PAM alkylated protein with respect to peptide recovery, compared with the original method with CAM post-alkylation.

Alkylation↗

PubMed1992

A new in situ hybridization technique for spliced RNA species documents the bone marrow origin of pulmonary macrophages in chronic myelogenous leukemia.

Tissue macrophages derive from monocytes of bone marrow origin. Because monocytes from patients with chronic myelogenous leukemia (CML) contain the Philadelphia chromosome (Ph), it seemed probable that tissue macrophages in CML would originate from the malignant clone. Using powerful molecular techniques, we studied pulmonary alveolar macrophages (PAM) from two patients with CML. PAM from Patient 1, a patient in chronic phase studied before bone marrow transplantation (BMT), contained the Ph by Southern blot analysis. Patient 2, an accelerated phase patient, was studied after post-BMT relapse. PAM from this patient not only contained the Ph, but also expressed the BCR/ABL message documented by a new splice junction in situ hybridization technique. This new technique allows detection of BCR/ABL mRNA and determination of splice useage in individual cells. These data confirm the continued replenishing of PAM from peripheral blood monocytes in non-BMT settings and represent the first direct evidence that tissue macrophages are derived from the malignant clone in patients with CML.

Adult↗