The impact of cattle dung pats on earthworm distribution in grazed pastures.

BACKGROUND: Grazed grassland management regimes can have various effects on soil fauna. For example, effects on earthworms can be negative through compaction induced by grazing animals, or positive mediated by increases in sward productivity and cattle dung pats providing a food source. Knowledge gaps exist in relation to the behaviour of different earthworm species i.e. their movement towards and aggregation under dung pats, the legacy effects of pats and the spatial area of recruitment. The present study addressed these knowledge gaps in field experiments, over 2 years, using natural and simulated dung pats on two permanent, intensively grazed pastures in Ireland. RESULTS: Dung pats strongly affected spatial earthworm distribution, with up to four times more earthworms aggregating beneath pats, than in the control locations away from pats. In these earthworm communities comprising 11 species, temporally different aggregation and dispersal patterns were observed, including absence of individual species from control locations, but no clear successional responses. Epigeic species in general, but also certain species of the anecic and endogeic groups were aggregating under dung. Sampling after complete dung pat disappearance (27 weeks after application) suggested an absence of a dung pat legacy effect on earthworm communities. Based on species distributions, the maximum size of the recruitment area from which earthworms moved to pats was estimated to be 3.8 m2 per dung pat. Since actual grazing over 6 weeks would result in the deposition of about 300 dung pats per ha, it is estimated that a surface area of 1140 m2 or about 11% of the total grazing area can be influenced by dung pats in a given grazing period. CONCLUSIONS: This study showed that the presence of dung pats in pastures creates temporary hot spots in spatial earthworm species distribution, which changes over time. The findings highlight the importance of considering dung pats, temporally and spatially, when sampling earthworms in grazed pastures. Published comparisons of grazed and cut grasslands probably reached incorrect conclusions by ignoring or deliberately avoiding dung pats. Furthermore, the observed intense aggregation of earthworms beneath dung pats suggests that earthworm functions need to be assessed separately at these hot spots.

[Pierre Robin Sequence: interdisciplinary treatment after prenatal diagnosis]. / Pierre Robin Sequenz: Pränatale Diagnostik und interdisziplinäre Therapie.

BACKGROUND: Pierre Robin Sequence (PRS) is characterised by mandibular micrognathia and/or retrognathia, glossoptosis and upper airway obstruction (UAO). In severe cases, UAO and cyanosis occur immediately after birth and endoscopic intubation may become necessary. Therefore, prenatal diagnosis with referral to a specialized department is important. METHOD: A non-invasive interdisciplinary treatment protocol is presented. The postnatal adjustment of the preepiglottic baton plate (PEBP) as early as possible is essential in this concept. EVIDENCE: In a randomised cross-over trial with 11 patients with isolated PRS, the PEBP was found to reduce the apnoea index significantly and to be superior to a conventional palatal plate. An uncontrolled longitudinal study indicated that the UAO had normalised 3 months after discharge; all infants showed adequate weight gain with bottle feeding. In a comparative study with 34 healthy children and 34 children with isolated PRS, no significant differences in cognitive outcome was found. CONCLUSIONS: Interdisciplinary co-operation between prenatal care, neonatology and orthodontics is a pre-requisite for optimal postnatal therapy. Complications of UAO can be avoided by early and adequate treatment, resulting in good results for feeding, speech and facial profile. Invasive surgical treatment options like tongue-lip-adhesion, mandibular extension or distraction should be obsolete.

An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.

30 years ago, investigations into the molecular basis of the delayed-type hypersensitivity reaction (DTH) provided evidence for the first lymphokine activity: a lymphocyte-derived mediator called macrophage migration inhibitory factor (MIF), which inhibited the random migration of peritoneal macrophages. Despite the long-standing association of MIF with the DTH reaction and the cloning of a human protein with macrophage migration inhibitory activity, the precise role of MIF in this classic cell-mediated immune response has remained undefined. This situation has been further complicated by the fact that two other cytokines, interferon gamma and IL-4, similarly inhibit macrophage migration and by the identification of mitogenic contaminants in some preparations of cloned human MIF. Using recently developed molecular probes for mouse MIF, we have examined the role of this protein in a classical model of DTH, the tuberculin reaction in mice. Both MIF messenger RNA and protein were expressed prominently in DTH lesions, as assessed by reverse transcription polymerase chain reaction, in situ hybridization, and immunostaining with anti-MIF antibody. The predominant cellular origin of MIF appeared to be the monocyte/macrophage, a cell type identified recently to be a major source of MIF release in vivo. The administration of neutralizing anti-MIF antibodies to mice inhibited significantly the development of DTH, thus affirming the central role of MIF in this classic immunological response.

The pathogenic role of macrophage migration inhibitory factor in immunologically induced kidney disease in the rat.

Macrophage migration inhibitory factor (MIF) plays a pivotal role in the inflammatory response in endotoxemia and in the delayed-type hypersensitivity response, but its potential as a regulator of immunologically induced disease is unknown. We have addressed this issue by administering a neutralizing anti-MIF antibody in a rat model of immunologically induced crescentic anti-glomerular basement membrane (GBM) glomerulonephritis. Six individual experiments using paired inbred littermates were performed. Rats were primed with rabbit immunoglobulin on day -5 and then injection with rabbit anti-rat GBM serum on day 0. Pairs of animals were treated with anti-MIF or a control monoclonal antibody from the time of anti-GBM serum administration until being killed 14 d later. Control antibody-treated animals developed severe proteinuria and renal function impairment with severe histological damage due to marked leukocytic infiltration and activation within the kidney. In contrast, anti-MIF treatment substantially reduced proteinuria, prevented the loss of renal function, significantly reduced histological damage including glomerular crescent formation, and substantially inhibited renal leukocytic infiltration and activation (all P <0.001 compared with control treatment). Inhibition of renal disease by anti-MIF treatment was attributed to preventing the marked upregulation of interleukin-1beta, leukocyte adhesion molecules including intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and inducible nitric oxide synthase expression seen in the control antibody-treated animals. This inhibition of progressive renal injury was mirrored by the complete suppression of the skin delayed-type hypersensitivity response to the challenge antigen (rabbit IgG). Interestingly, anti-MIF treatment did not effect the secondary antibody response or immune deposition within the kidney, indicating that MIF participates in cellular-based immunity in this primed macrophage-dependent anti-GBM glomerulonephritis. In conclusion, this study has demonstrated a key regulatory role for MIF in the pathogenesis of immunologically induced kidney disease. These results argue that blocking MIF activity may be of benefit in the treatment of human rapidly progressive glomerulonephritis, and suggest that MIF may be important in immune-mediated disease generally.

[Treatment of infants with Pierre Robin sequence]. / Therapeutisches Vorgehen bei Pierre-Robin-Sequenz.

The Pierre Robin sequence (PRS) characterized by mandibular micro- or retrognathia and glossoptosis with or without cleft palate, presents clinically with intermittent upper airway obstruction (UAO). It is associated with other malformations in about half the cases. The incidence is about 1:8,500. Isolated PRS without other malformations does not, by itself, appear to affect neurodevelopment. Active intervention may therefore be required to reduce the risk for neurocognitive impairment resulting from UAO. Current treatment options for UAO range from prone positioning, use of a nasopharyngeal tube, glossopexy via tongue lip adhesion, mandibular distraction to tracheostomy. An effective, non-invasive treatment protocol which includes implementation of an intraoral orthodontic appliance with velar extension (the pre-epiglottic baton plate; PEBP) is presented in this article.

Pushing the limits: Quantification of chromophores in real-world paper samples by GC-ECD and EI-GC-MS.

Widening the methodology of chromophore analysis in pulp and paper science, a sensitive gas-chromatographic approach with electron-capture detection is presented and applied to model samples and real-world historic paper material. Trifluoroacetic anhydride was used for derivatization of the chromophore target compounds. The derivative formation was confirmed by NMR and accurate mass analysis. The method successfully detects and quantifies hydroxyquinones which are key chromophores in cellulosic matrices. The analytical figures of merit appeared to be in an acceptable range with an LOD down to approx. 60ng/g for each key chromophore, which allows for their successful detection in historic sample material.

Age-dependence of urinary normal and modified nucleosides in childhood as determined by reversed-phase high-performance liquid chromatography.

Modified nucleosides have been characterized as tumor markers for a number of malignant diseases. In order to use these markers in children, the age-dependence of the nucleoside levels in healthy children has to be established and taken into account in diagnostic decisions. In this study, the levels of 12 normal and modified nucleosides in urine of 166 healthy children and adolescents with an age between 1 day and 19 years are determined by reversed-phase HPLC, and age-dependent reference ranges are defined. The urinary nucleoside concentrations are related to the creatinine concentrations, which allows the use of randomly collected urine samples. All nucleoside levels in urine of children decrease with age, most pronounced during the first 4 years of life, and the age-dependence of the reference values of the individual nucleosides can be approximated by a mathematical function y = b(0) + b(1) (1/x) with the regression coefficients b(0) and b(1,) the nucleoside levels y and the age x between 1 year and 19 years. In the very young children, the shifts in the nucleoside concentrations are more differentiated. Starting with low levels on the first day of life, the concentrations of all studied nucleosides rise up to an age of 1-2 months, when they reach their absolute maximum for all age periods, and then decrease.

Macrophage migration inhibitory factor production by Leydig cells: evidence for a role in the regulation of testicular function.

Macrophage migration inhibitory factor (MIF), described originally as a product of activated T lymphocytes, recently has been found to be released by monocytes/macrophages and the anterior pituitary gland. Immunohistochemical studies of the adult rat testis using an affinity-purified polyclonal antimurine MIF antibody demonstrated strong staining for MIF in Leydig cells and their putative precursors. Peritubular myoid cells and the seminiferous epithelium were negative for MIF staining; however, a weak reaction around the heads of elongated spermatids also was observed. The expression of MIF messenger RNA and protein in whole rat testis was demonstrated by Northern blot and Western blot analyses, respectively. Both MIF messenger RNA and protein immunoreactivity in Leydig cells was observed in testes obtained from long term hypophysectomized rats. Significant concentrations of intracellular MIF were detected in lysates of the TM3 Leydig cell line (7.23 +/- 2.6 pg/microgram protein), and testicular interstitial fluid contained 14.7 +/- 1.6 ng/ml MIF protein, as measured by MIF-specific enzyme-linked immunosorbent assay. To gain insight into the possible biological role of MIF in the testis, cultures of adult rat seminiferous tubules and purified Leydig cells were incubated together with recombinant murine MIF (rMIF). Neither rMIF (50 ng/ml) nor a neutralizing anti-MIF antiserum was found to affect basal or LH-stimulated Leydig cell steroidogenesis in vitro. However, a dose-dependent decrease in the secretion of inhibin by the seminiferous tubules was observed at rMIF concentrations ranging from 10-100 ng/ml. Taken together, these data indicate that Leydig cells produce MIF in vivo and suggest an important regulatory role for this newly discovered mediator of testicular function.

T-lymphocyte subsets in the duodenal lamina propria of patients infected with the human immunodeficiency virus type 1 and influence of high-dose immunoglobulin therapy.

T-lymphocyte subsets in duodenal biopsies of human immunodeficiency virus type 1 (HIV-1)-infected patients were studied by immunocytochemical staining to determine the alterations of CD4- and CD8-cell subsets in comparison with HIV-1 antibody-negative controls and to examine the association with stage, gastrointestinal symptoms, and peripheral lymphocyte subsets and the influence of high-dose intravenous immunoglobulins. A significant decrease in duodenal CD4 cells (p less than 0.001) and CD4/CD8 ratio (p less than 0.001) follows HIV-1 infection when compared to HIV-1-negative controls, more accentuated both in patients of stage WR6 and suffering from diarrhea than in those of stages WR1-5 or without diarrhea. In addition, a significant increase in CD8 cells (p less than 0.01) could be found in HIV-1-infected patients, again with lower levels in patients of stages WR6 than WR1-5. A strong correlation was found between the intestinal and peripheral CD4/CD8 ratio (R = 0.80), but the correlation was weak if HIV-1-negative persons were excluded from analysis (R = 0.29). Treatment with high-dose intravenous immunoglobulins improved diarrhea in four of five patients; two patients gained weight. Diffuse lymphocytic infiltration of the lamina propria, villous atrophy, CD4- and CD8-cell percentage, and CD4/CD8 ratio were not influenced.

Macrophage migration inhibitory factor expression in human renal allograft rejection.

BACKGROUND: Macrophage migration inhibitory factor (MIF) plays a pivotal role in immune-mediated diseases. Despite the long-standing association of MIF with the delayed-type hypersensitivity response, the potential role of MIF in allograft rejection is unknown. METHODS: MIF expression was assessed by in situ hybridization and immunohistochemistry staining in 62 biopsies of human renal allograft rejection and in normal human kidney. RESULTS: MIF mRNA and protein is constitutively expressed in normal kidney, being largely restricted to tubular epithelial cells, some glomerular epithelial cells, and vascular smooth muscle cells. In both acute and chronic renal allograft rejection, there was marked up-regulation of MIF mRNA and protein expression by intrinsic kidney cells such as tubular epithelial cells and vascular endothelial and smooth muscle cells. There was also MIF expression by infiltrating macrophages and T cells. Of note, macrophage and T cell infiltrates were largely restricted to areas with marked up-regulation of MIF expression, potentially contributing to the development of severe tubulitis and intimal or transmural arteritis. Quantitative analysis found that increased MIF expression in allograft rejection gave a highly significant correlation with macrophage and T cell accumulation in both the glomerulus and interstitium (P<0.001). In addition, the number of MIF+ tubules and interstitial MIF+ cells correlated significantly with the severity of allograft rejection (P<0.01), and the loss of renal function (P<0.01). In contrast, no up-regulation of renal MIF expression and no leukocyte accumulation was seen in allograft biopsies without evidence of rejection. CONCLUSIONS: This is the first study to demonstrate that local MIF expression is up-regulated during allograft rejection. The association between up-regulation of MIF expression, macrophage and T cell infiltration and the severity of renal allograft rejection suggests that MIF may be an important mediator in the process of allograft rejection.

Effect of forty-eight-hour glucose infusion into rats on islet ion fluxes, ATP/ADP ratio and redox ratios of pyridine nucleotides.

Glucose infusion into rats has been shown to sensitize/desensitize insulin secretion in response to glucose. In pancreatic islets from glucose-infused rats (GIR) (48 h, 50%, 2 ml/h) basal insulin release (2.8 mmol/l glucose) was more than fourfold compared with islets from saline-infused controls and the concentration-response curve for glucose was shifted to the left with a maximum at 11.1 mmol/l. The concentration-response curve for 45Ca2+ uptake was also shifted to the left in islets from GIR with a maximum at 11.1 mmol/l glucose. Starting from a high basal level at 2.8 mmol/l glucose KCl produced no insulin release or 45Ca2+ uptake in islets from GIR. Islets from GIR exhibited a higher ATP/ADP ratio in the presence of 2.8 mmol/l glucose and marked inhibition of 86Rb+ efflux occurred even at 3 mmol/l glucose. Moreover, in islets from GIR the redox ratios of pyridine nucleotides were increased. On the other hand insulin content was reduced to about 20%. The data suggest that a 48-h glucose infusion sensitizes glucose-induced insulin release in vitro in concentrations below 11.1 mmol/l. This may, at least in part, be due to enhanced glucose metabolism providing increased availability of critical metabolic factors including ATP which, in turn, decrease the threshold for depolarization and therefore calcium uptake. Calcium uptake may then be further augmented by elevation of the redox state of pyridine nucleotides.

Programmed cell death (apoptosis) in human monocytes infected by influenza A virus.

Although infection of monocytes by influenza A virus primes for a high cytokine release, it also leads to cell death within 20-30 hours. In this brief report, we demonstrate that influenza A virus-induced monocyte killing was due to programmed cell death (apoptosis) and not to necrosis. Morphologically, chromatin condensation and margination occurred and biochemically, an apoptosis-specific internucleosomal DNA fragmentation into multimers of 180 bp ("DNA ladder") was found. Induction of apoptosis and not necrosis in influenza A virus-infected monocytes may serve three purposes: 1. Virus replication is limited, 2. a priming for a high cytokine response is initiated and 3. damaging and inflammation-inducing lysosomal enzymes are held back from monocytes undergoing controlled cell death.

Expression of transcription factor genes after influenza A virus infection.

Infection of human monocytes with influenza A virus induces a broad range of proinflammatory cytokines and mononuclear cell attracting chemokines before the infected cells undergo apoptosis. The underlying mechanisms by which the corresponding genes are transcriptionally initiated after virus infection are still poorly understood. Activation of NF-kappa B seems to play an important role in the regulation of many proinflammatory cytokine genes, but cannot be the only mechanism, since several cytokine genes lack respective binding sites in their promoter regions. Therefore, we additionally investigated other transcription factors of possible importance such as CREB, CTF, OTF-1, and OTF-2. To explore long-term regulatory mechanisms, we investigated the induction of transcription factors on the gene expression level which may be important to substitute for metabolized transcription factor proteins after their activation. We identified a cell-type-specific differential response: CREB, CTF, OTF-1, OFT-2, and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6, while in freshly prepared human monocytes no significant changes were detected. In infected monocytes, which die by apoptosis, the expression of CREB, CTF, and OTF-2 was rather suppressed 8 hours after infection. In conclusion, the long-term regulation of transcription factor gene expression in non-proliferating cells seems to be of minor importance after influenza infection since in apoptosisprone cells an immediate availability of transcription factor proteins is required.

Disturbances of motor preparation in basal ganglia and cerebellar disorders.

Movements of the arms (execution) in standing human subjects are preceded (preparation), accompanied, and followed (compensation) by muscular activity in postural trunk and leg muscles. Postural muscular activity compensates inertial forces acting on the body at the beginning and during arm movements and keeps the centre of gravity within the limits of stable upright standing. Standing normal subjects and patients performed bilateral arm elevations in response to an acoustic trigger. The beginning of EMG activity in the anterior deltoid muscle reflects the reaction time. Postural activity prior to the arm movement was observed in anterior tibialis, paraspinalis, and hamstring muscles. Compensatory muscular action occurred in the triceps surae. Motor preparation and compensation thus are an integral part of a motor programme. Muscles involved, latencies, and amount of EMG activity change with variations in the motor task (e.g. range of arm movement, changes in inertia of the arm, changes in initial body position). Reaction times and the pattern of preparatory and compensatory postural EMG activity were normal in most of the patients with Parkinson's disease. Reaction times were significantly increased in patients with cerebellar atrophy. The most prominent pathological feature in cerebellar patients was the inadequate temporal sequence of motor preparation and execution. Our results indicate that the basal ganglia play a minor role in motor preparation, whereas the cerebellum seems to coordinate the relative timing between motor preparation and execution.

Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines.

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.

Expression and glucocorticoid regulation of macrophage migration inhibitory factor (MIF) in hippocampal and neocortical rat brain cells in culture.

The biosynthesis of macrophage-migration inhibitory factor (MIF) and its regulation by the glucocorticoid dexamethasone was examined in cultured hippocampal and neocortical embryonic rat cells. Using immunohistochemical methods, MIF was found to be localized in neuronal as well as in non-neuronal cells. During the whole 12 day culture period, levels of MIF transcripts were detectable in both hippocampal and neocortical cells with an apparent increase in extracellular MIF protein at the later time points examined. Treatment with even very low concentrations (10(-11) M) of dexamethasone did not alter MIF mRNA levels but resulted in a rapid release of intracellular MIF protein within 1 and 4 h and a subsequent replenishment after 24 h. These data suggest that glucocorticoids do not affect the transcriptional activity of the MIF gene but induce the secretion of the protein, which suggests a close functional relationship of both mediators in the CNS.

Twenty-four-hour tremor recordings in the evaluation of the treatment of Parkinson's disease.

A new method of prolonged recording of EMG provides a good estimate of spontaneous and induced diurnal variations in resting tremor in Parkinson's disease. It provides a record and a measure of the effects of treatment. Tremor intensity shows considerable variations even over short periods of time. Therefore short-term measurements of tremor are unhelpful. Long-term recordings agree better with the patient's assessment than with the clinical rating score. Repeated recordings over a similar 10-h period on 3 consecutive days in one patients showed fairly constant measures of occurrence and intensity of tremor. In contrast to accelerometer measurements of tremor, artefacts caused by movements and general activity of the patient do not materially interfere with tremor evaluation using surface EMG.

The coordination of posture and voluntary movement in patients with hemiparesis.

Postural adjustments associated with the task of raising oneself on tiptoes were investigated in a reaction time paradigm in six normal subjects and six patients with hemiparesis due to stroke. Body and ankle position in space were measured by means of a movement analysis system (ELITE). The findings indicate that the task of going up on tiptoes is performed in two steps. First, the centre of gravity is shifted forward to a position perpendicular to the forefoot. This movement is initiated by a phasic burst of EMG activity in the tibialis anterior (TA). The activity of the quadriceps femoris (QUA) aids the forward shift and together with the biceps femoris (BF) stabilizes the knee. Following these postural adjustments, the action of going up on tip-toes is performed mainly by the gastrocnemius medialis (MG). The basic pattern of preparatory (TA, QUA, BF) and focal (MG) activity was disturbed in its temporal sequence in patients with hemiparesis. The analysis of the biomechanical data showed smaller movement velocities for leaning forward and going up on tiptoes in patients, with increased movement amplitude on the paretic side. In addition, the correlation between the start of horizontal (leaning forward) and vertical (going up on tiptoes) hip movement was lost in patients. The preserved correlation between the latency of MG activity and the onset of the vertical hip movement on the paretic side in patients and the loss of correlation on the non-paretic side indicates that the EMG activity on the healthy side is adapted to the functional requirements of the affected side.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of ataxia in alcoholic cerebellar atrophy through alcohol abstinence.

Postural instability was measured and short, medium and long latency EMG responses to angular displacement of the ankle were recorded from leg muscles in a group of 17 alcoholics who presented with clinical signs of cerebellar atrophy of the anterior lobe. Recordings were performed twice (average interval 18.5 months) to determine the effects of continued drinking versus abstinence on the signs of the cerebellar damage. Patients who were abstinent (n = 11) exhibited a significant, sometimes dramatic decrease of body sway whereas patients who continued drinking (n = 6) showed increased body sway when the eyes were closed. Short and medium latency EMG responses were unaltered in both groups of patients. The integral of the long latency response of the antagonist tended to increase with continued abuse and to decrease in abstinent patients.

Relationship of calcitonin mRNA expression to the differentiation state of HL 60 cells.

Raised plasma levels of immunoreactive human calcitonin (ihCT) can be found in patients with myeloid leukemia and seem to indicate a poor prognosis. High levels were found in acute undifferentiated and acute myeloblastic leukemia. To test whether CT expression could be a marker of myeloid differentiation, we used the promyelocytic leukemia cell line HL 60 which also expresses ihCT as a model system for myeloid differentiation. Exponentially growing HL 60 cells as well as differentiation induced HL 60 cells expressed a single 1.0 Kb CT transcript. The induction of HL 60 cell differentiation along the granulocytic lineage by DMSO or HMBA had no effect on the level of CT transcripts. Induction of monocytic/macrophagic differentiation by TPA resulted in a transient, about 10-fold elevated expression of CT steady state mRNA after 24 h. In contrast to TPA, induction of HL 60 cell differentiation along the monocytic pathway by Vit D3 had no detectable effect on the level of the CT in RNA expression at corresponding time points. These findings suggest that the transient induction of CT steady state mRNA expression by TPA is rather a direct effect of the phorbol ester than commitment along the monocytic line of differentiation.