Depression and anxiety symptoms remained elevated after 10 months of the COVID-19 pandemic in southern Brazil: findings from the PAMPA cohort.

OBJECTIVES: This study aimed to examine the changes in depression and anxiety symptoms among Brazilian adults over 10 months of the COVID-19 pandemic. STUDY DESIGN/METHODS: The present study used data from wave 1 (June/July 2020) and wave 2 (December 2020/January 2021) of the Prospective Study About Mental and Physical Health (PAMPA) Cohort, a state-level, ambispective longitudinal study with adults from southern Brazil. The frequency of anxiety and depressive symptoms was assessed using the Hospital Anxiety and Depression Scale. Anxiety and depressive symptoms before social distancing were retrospectively assessed during wave 1. RESULTS: Most of the 674 participants were classified as non-symptomatic for depressive (85.0%) and anxiety symptoms (73.2%) before the COVID-19 pandemic. At wave 1, there were increases in symptoms of depression (7.6% [95% confidence interval [CI]: 7.2%, 8.1%]) and anxiety (9.1% [95% CI: 8.6%, 9.5%]). These decreased at wave 2 (depression: 6.9% [95% CI: 6.5%, 7.2%]; anxiety: 7.4% [95% CI: 7.1%, 7.8%]) although they were still elevated compared with pre-COVID (depression: 4.5% [95% CI: 4.2%, 4.8%]; anxiety: 5.8% [95% CI: 5.5%, 6.1%]). Adults living alone (b = 0.44 [95% CI: 0.07, 0.82]) had a faster trajectory in anxiety symptoms than their counterparts. Cohort members who were living alone (b = 0.24 [95% CI: 0.06, 0.42]) and with diagnosed chronic disease (0.32 [95% CI: 0.18, 0.46]) had a faster increase in depressive symptoms than their respective counterparts. Participants aged ≥60 years showed a slower trajectory of depressive (b = -0.46 [95% CI: -0.73, -0.18]) and anxiety (b = -0.61 [95% CI: -1.20, -0.02) symptoms. CONCLUSIONS: During 10 months of COVID-19, anxiety and depression symptoms improved but were still higher than before COVID-19.

Prevalence and Severity of Ratoon Stunt in Commercial Brazilian Sugarcane Fields.

Brazil has 9 million ha of sugarcane, 85% of which are located in the Center-South area of the country. Field trials and surveys around the globe have shown that ratoon stunt disease (RSD), caused by Leifsonia xyli subsp. xyli, can severely reduce tonnage yield. Previous small-scale studies in Brazil have demonstrated RSD infection in all varieties, with values varying from 25 to 68%. Nevertheless, the prevalence and severity of RSD in commercial fields had not previously been assessed. To address this issue, we surveyed 13,173 ha in 1,154 fields of the eight main sugarcane varieties of the Center-South area, taking 92,114 samples from 50 mills in five different states. Our data showed that 10% of fields were infected, and that 58% of mills had at least one RSD-infected field. The variety RB92579 had the highest proportion of infected fields (17%) and, on average, the prevalence and severity in these fields was high compared with other varieties. RB867515, the most cultivated in Brazil, showed infection in 6.2% of sampled fields (5.5% of sampled area) causing an estimated annual economic loss of over US$1 million. This was the first time the economic importance of RSD on Brazilian commercial sugarcane production was estimated. The Cerrado region had the highest prevalence of RSD: 16% of fields, 17% of the cultivated area, and 82% of mills. The use of diseased planting material was identified in 9% of plant cane fields, representing 10% of the cultivated area. Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Rosiglitazone modulates pigeon atherosclerotic lipid accumulation and gene expression in vitro.

Atherosclerosis is a major contributor to the overall United States mortality rate, primarily in the form of heart attacks and stroke. Unlike the human disease, which is believed to be multifactorial, pigeon atherosclerosis is due to a single gene autosomal recessive trait. The White Carneau (WC-As) strain develops atherosclerotic plaques without the presence of known environmental risk factors such as diet and classic predictors such as blood pressure or blood cholesterol levels. With similar parameters, the Show Racer (SR-Ar) is resistant to plaque development. Thiazolidinediones, including rosiglitazone, activate the peroxisome proliferator-activated receptor gamma (PPARγ) raising cellular sensitivity to insulin. The effect of rosiglitazone was evaluated in aortic smooth muscle cells (SMC) from these 2 pigeon breeds. Primary SMC cultures were prepared from WC-As and SR-Ar squabs. Cell monolayers, which achieved confluence in 7 d, were treated with 0 or 4 µM rosiglitazone for 24 h. Cellular lipid accumulation was evaluated by oil red O staining. Control WC-As cells had significantly higher vacuole scores and lipid content than did the SR-Ar control cells. Rosiglitazone treatment decreased WC-As lipid vacuoles significantly compared with the control cells. On the other hand, lipid vacuoles in the treated and untreated SR-Ar cells did not differ significantly. The effect of rosiglitazone on WC-As SMC gene expression was compared with control SMC using representational difference analysis. Significant transcript increases were found for caveolin and RNA binding motif in the control cells compared with the rosiglitazone-treated cells as well as cytochrome p450 family 17 subfamily A polypeptide 1 (CYP171A) in the rosiglitazone-treated cells compared with the control cells. Although rosiglitazone was selected for these experiments because of its role as a PPARγ agonist, it appears that the drug also tempers c-myc expression, as genes related to this second transcription factor were differentially expressed. Both PPARγ and c-myc appear to affect WC-As SMC gene expression, which may relate to disease development, progression, or both.

Objectively measured patterns of physical activity in primary school children in Coventry: the influence of ethnicity.

AIMS: The aetiology of increased metabolic risk in South Asians is incompletely understood, but may include modifiable factors such as physical activity. This study assessed patterns of physical activity in UK primary school children and examined the influence of ethnicity. METHODS: We studied a community sample of children aged 8-9 years attending primary schools in Coventry, UK. One hundred and sixty-one children wore combined physical activity and heart rate monitors for 7 days. Levels of activity and energy expenditure were compared between White European (n = 96) and South Asian children (n = 65). Patterns of physical activity during the school week were also described. RESULTS: Seventy-three per cent of White Europeans compared with only 35% of South Asians achieved international recommendations of 60 minutes of moderate to vigorous physical activity daily (P < 0.0000). South Asians were less active during the week (106 ± 28 vs. 120 ± 32 counts/min, respectively, P = 0.0054) and at weekends (92 ± 34 vs. 108 ± 54 counts/min, P = 0.0118) compared with White Europeans. There were differences in energy expenditure with lower physical activity levels in South Asians (daily average 1.68 ± 0.13 vs. 1.76 ± 0.17, P < 0.0001). Differences were attributable to less activity after school in South Asians (97 ± 29 vs. 120 ± 43 counts/min, P < 0.0000) as daytime activity was comparable between groups (120 ± 41 vs. 124 ± 39 counts/min, P > 0.05). CONCLUSION: South Asian children in Coventry do significantly less physical activity than White Europeans, mainly attributable to differences in after-school activity. Ethnically tailored interventions should explore whether physical activity can be increased in South Asian children and, if so, whether this increased physical activity improves metabolic health.

Feedback or biofeedback to augment pelvic floor muscle training for urinary incontinence in women: shortened version of a Cochrane systematic review.

BACKGROUND: Feedback and biofeedback (BF) are common adjuncts to pelvic floor muscle training (PFMT) for women with stress, urgency, and mixed urinary incontinence (UI). An up to date systematic review of adjunctive feedback or BF was needed to guide practice and further research. OBJECTIVES: To determine whether feedback or BF add benefit to PFMT for women with UI. METHODS: The Cochrane Incontinence Group Specialised Trials Register was searched (May 2010) for randomised or quasi-randomized trials in women with stress, urgency or mixed UI regardless of cause, which compared PFMT versus PFMT augmented with feedback or BF. Two reviewers independently undertook eligibility screening, risk of bias assessment and data extraction. Analysis was in accordance with the Cochrane Handbook for Systematic Reviews of Intervention (version 5.0.2). RESULTS: Twenty-four trials were included, and many were at moderate to high risk of bias. Women who received BF were less likely to report they were not improved (RR 0.75, 95% CI: 0.66-0.86), although there was no statistically significant difference for cure (RR 0.92, 95% CI: 0.81-1.05) and marginal statistical significance for leakage episodes (mean difference: -0.12 leaks/day, 95% CI: -0.22 to -0.01). It is possible the results are confounded because women in the BF group commonly had more contact with the health professional than those in the PFMT only arm. CONCLUSION: BF may add benefit to PFMT but the observed effect could well be related to another variable, such as the amount of health professional contact rather than the BF per se.

Investigation of contact acoustic nonlinearities on metal and composite airframe structures via intensity based health monitoring.

Nonlinear structural intensity (NSI) and nonlinear structural surface intensity (NSSI) based damage detection techniques were improved and extended to metal and composite airframe structures. In this study, the measurement of NSI maps at sub-harmonic frequencies was completed to provide enhanced understanding of the energy flow characteristics associated with the damage induced contact acoustic nonlinearity mechanism. Important results include NSI source localization visualization at ultra-subharmonic (nf/2) frequencies, and damage detection results utilizing structural surface intensity in the nonlinear domain. A detection metric relying on modulated wave spectroscopy was developed and implemented using the NSSI feature. The data fusion of the intensity formulation provided a distinct advantage, as both the single interrogation frequency NSSI and its modulated wave extension (NSSI-MW) exhibited considerably higher sensitivities to damage than using single-sensor (strain or acceleration) nonlinear detection metrics. The active intensity based techniques were also extended to composite materials, and results show both NSSI and NSSI-MW can be used to detect damage in the bond line of an integrally stiffened composite plate structure with high sensitivity. Initial damage detection measurements made on an OH-58 tailboom (Penn State Applied Research Laboratory, State College, PA) indicate the techniques can be transitioned to complex airframe structures achieving high detection sensitivities with minimal sensors and actuators.

Atherosclerosis-susceptible and atherosclerosis-resistant pigeon aortic cells express different genes in vivo.

Spontaneous atherosclerosis in the White Carneau (WC-As) pigeon is inherited as a single gene disorder, and its progression closely mirrors the human disease. Representational difference analysis and microarray were used to identify genes that were differentially expressed between the susceptible WC-As and resistant Show Racer (SR-Ar) aortic tissue. The RNA extracted from 1-d-old squab aortas was used to make cDNA for each experiment. Fifty-six unique genes were found using representational difference analysis, with 25 exclusively expressed in the WC-As, 15 exclusive to the SR-Ar, and 16 nonexclusive genes having copy number variation between breeds. Caveolin and ß-actin were expressed in the WC-As, whereas the proteasome maturation protein and the transcription complex CCR4-NOT were exclusive to the SR-Ar. Microarray analysis revealed 48 genes with differential expression. Vascular endothelial growth factor and p53 binding protein were among the 17 genes upregulated in the WC-As. Thirty-one genes were upregulated in the SR-Ar including the transforming growth factor-ß signaling factor SMAD2 and heat shock protein 90. Genes representing several biochemical pathways were distinctly different between breeds. The most striking divergences were in cytoskeletal remodeling, proteasome activity, cellular respiration, and immune response. Actin cytoskeletal remodeling appears to be one of the first differences between susceptible and resistant breeds, lending support to the smooth muscle cell phenotypic reversion hypothesis of human atherogenesis.

Differentially expressed genes in aortic smooth muscle cells from atherosclerosis-susceptible and atherosclerosis-resistant pigeons.

Susceptibility to spontaneous atherosclerosis in the White Carneau (WC-As) pigeon shows autosomal recessive inheritance. Aortic smooth muscle cells (SMC) cultured from susceptible WC-As and resistant Show Racer (SR-Ar) pigeons exhibit developmental and degenerative features corresponding to the respective SMC at atherosclerosis-prone sites in vivo. We used representational difference analysis to identify differentially expressed genes between WC-As and SR-Ar aortic SMC. Total RNA was extracted from cultured primary SMC of each breed, converted to double-stranded cDNA, followed by direct comparison in reciprocal representational difference analysis experiments. Difference products were cloned, sequenced, and identified by BLAST against the chicken genome. Six putative biochemical pathways were distinctly different between breeds with genes involved in energy metabolism and contractility exhibiting the most striking disparity. Genes associated with glycolysis and a synthetic SMC phenotype were expressed in WC-As cells. In contrast, SR-Ar cells expressed genes indicative of oxidative phosphorylation and a contractile SMC phenotype. In WC-As cells, the alternatives of insufficient ATP production limiting contractile function or the lack of functional contractile elements downregulating ATP synthesis cannot be distinguished due to the compressed in vitro versus in vivo developmental time frame. However, the genetic potential for effectively coupling energy production to muscle contraction present in the resistant SR-Ar was lacking in the susceptible WC-As.

Erector spinae plane block with catheter infusion for analgesia in a patient undergoing transaxillary first rib resection.

Analgesia for first rib resection can be challenging with short- and long-term consequences for patients such as acute distress, difficulty participating in physiotherapy and chronic pain. We report utilising an erector spinae plane block with a continuous infusion catheter as analgesia for a transaxillary first rib removal in a patient with venous thoracic outlet syndrome (Paget-Schroetter syndrome). We could find no reports of erector spinae plane block in transaxillary rib resection, and a limited number of reports using a paravertebral approach to analgesia for this procedure. In our case, an erector spinae plane block provided effective analgesia, allowing the patient to participate freely in postoperative physiotherapy; no complications of erector spinae plane block were encountered. Further research into the safety and efficacy of erector spinae plane block for first rib resection is warranted.

Neurocognition and the Suicidal Process.

Early thinking about cognitive process and suicidal behaviors tended to focus on the immediate situation surrounding the individual - typically the underlying psychiatric condition that was seen as leading to his or her distress. However, we now know that the cognitive processes involved in a range of suicidal thoughts and behaviors can exert a significant impact on the expression or development of these behaviors, even without an environmental stressor or psychiatric condition. In this chapter, we summarize theoretical perspectives that led to this realization and explore the current understanding of the link between cognition and suicide from recent research and clinical findings. We present these findings first by psychiatric disorder, then by cognitive domains, and finally by specific suicidal construct in order to highlight the importance of these factors in determining the role of cognition in the suicidal process.Within and across psychiatric disorders, certain cognitive processes - negativistic thinking, impulsivity, cognitive rigidity, and altered emotional processing - are frequently found to be linked to suicidal thoughts and behaviors. Overall cognitive performance, decreased processing speed, executive dysfunction, and negative biases in memory and attention have also been linked to suicidal thoughts and behaviors. However, these findings do not hold true for all populations. There seems to be a role both for cognitive distortions (such as hopelessness) and neurocognitive deficits (such as poor overall cognitive performance, slower processing speed, and executive dysfunction) in the suicidal process, which warrant further exploration both separately and together.

Differentially expressed soluble proteins in aortic cells from atherosclerosis-susceptible and resistant pigeons.

Soluble proteins in aortic smooth muscle cells cultured from atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were extracted and separated on 2-dimensional electrophoresis gels. Spots were analyzed with Phoretix software and compared between the 2 breeds. Proteins differentially expressed were arrayed on a map, plotting molecular weight against isoelectric point. Eight discrete zones were identified, 5 that included only proteins unique to susceptible cells and 3 that included proteins unique to resistant cells. Of the 88 differentially expressed proteins from susceptible cells, 41 were located in unique zones, whereas 29 of 82 differentially expressed proteins from resistant cells were in unique zones. Selected proteins from susceptibility, and resistance zones were annotated by peptide mass fragments, molecular weights, isoelectric points, and correspondence with genes differentially expressed between cells from the 2 breeds. Some of the annotated proteins (such as smooth muscle myosin phosphatase, myosin heavy chain, fatty acid-binding protein, ribophorin, heat shock protein, and tumor necrosis factor alpha-inducing factor) corresponded to the current hypotheses to explain atherogenesis. In addition, the unique electrophoretic migration zones of proteins associated with susceptibility or resistance should prove useful as a diagnostic tool in clinical settings where species or phenotypes, or both, susceptible or resistant to atherosclerosis can be identified.

Lack of clinical efficacy of rituximab in the treatment of autoimmune neutropenia and pure red cell aplasia: implications for their pathophysiology.

We describe 11 patients with severe refractory autoimmune cytopenias treated with the anti-CD20 monoclonal antibody rituximab. Six patients had autoimmune neutropenia (AIN), two had pure red cell aplasia (PRCA), one had AIN and autoimmune haemolytic anaemia, one had AIN and immune thrombocytopaenia purpura (ITP) and one had PRCA and ITP. Rituximab was administered at a dose of 375 mg/m(2) as an intravenous infusion weekly for 4 weeks. Six of eight patients with AIN and all three patients with PRCA did not respond. Two patients died: one with resistant AIN and autoimmune haemolytic anaemia died of pneumocytis pneumonia infection, and one with PRCA and ITP died of an acute exacerbation of bronchiectasis. Rituximab in AIN and PRCA appears to be less effective than Campath-1H when compared to historical data from our group. This supports the hypothesis that T cells may be important in the pathophysiology of AIN and PRCA.

Marrow transplants from matched unrelated donors for aplastic anaemia using alemtuzumab, fludarabine and cyclophosphamide based conditioning.

Graft failure, regimen-related toxicity and graft-versus-host disease (GVHD) are the critical barriers to unrelated donor transplants for aplastic anaemia (AA). We investigated the use of a novel conditioning regimen consisting of alemtuzumab (humanized CD52 antibody), fludarabine and cyclophosphamide in seven patients with AA, who underwent bone marrow transplant procedure using matched unrelated donors. The aetiology of AA was acquired (n=3), Fanconi's (n=3) and congenital (n=1). Median age was 13 years (range 8-35). All the donors were fully matched for HLA class I and II antigens using high-resolution typing. All the patients engrafted at a median of 18 days (range 13-35). Two patients died of transplant-related complications: one of adenovirus disease and the other developed extensive chronic GVHD of skin followed by cytomegalovirus (CMV) disease. Three patients developed Grade II acute GVHD disease (GVHD); none had Grade III-IV acute GVHD. Of the six evaluable patients, only one developed chronic GVHD. We conclude that this conditioning regimen for unrelated donor transplants for AA is sufficiently immunosuppressive to allow stable engraftment and appears to have a favourable impact on the incidence and severity of GVHD, warranting further investigation.

Interaction of granulocyte-macrophage colony-stimulating factor and interleukin 3 in human long-term bone marrow culture.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), or a combination of both growth factors were added weekly to normal human long-term bone marrow cultures (LTBMC). GM-CSF had a greater effect on the total nonadherent cell population than the committed progenitor cells (granulocyte-macrophage colony-forming units, CFUgm), whereas IL-3 had the opposite effect and stimulated the expansion of greater numbers of CFUgm than GM-CSF. The combination of both factors had an additive effect on CFUgm. The longevity of the growth factor-treated cultures was not reduced. These data indicate that IL-3 stimulates an earlier progenitor cell population than GM-CSF and that a combination of the two factors should be more effective in vivo and could be applied to the expansion of bone marrow progenitor cells in culture before bone marrow transplantation.

c-kit protein (stem cell factor receptor) expression on cells with erythroid characteristics and on normal human bone marrow without the use of monoclonal antibodies.

Stem cell factor (SCF) is a determining and crucial element in the development of early hematopoietic cells. The SCF receptor protein has been identified as the product of the protooncogene c-kit and has been detected using monoclonal antibodies (MAbs) on a broad selection of erythroid, myeloid, and lymphoid cell lines as well as on bone marrow mononuclear cells (BMMNC). SCF is known to increase both the number and size of burst-forming unit-erythroid (BFU-E) colonies in normal human BM culture in a dose-dependent fashion. A detailed study of the involvement of SCF and its receptor c-kit in normal erythropoiesis will help elucidate intrinsic irregularities of anemias such as Diamond Blackfan Anemia, an aregenerative congenital anemia. Abnormalities of this heterogeneous disorder are confined to the red cell lineage and are thought to arise through a defect at the stem/progenitor cell level. Our in vitro studies suggest that SCF therapy will influence BFU-E production in at least a portion of these patients, although in another group, SCF response is limited or absent. Additionally, further investigations have shown a possible c-kit signaling defect that clearly necessitates further c-kit characterization. To parallel this, we, therefore, attempted to study the relationship of c-kit with its ligand. This report describes a nonradioactive method for detecting SCF receptors that varies from conventional assays in that the fluorescent label conjugated to the SCF/c-kit complex is connected via an extended-ester linkage that reduces steric influence and promotes full normal structural ligand binding of the SCF to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

The novel monoclonal antibody By114 helps detect the early emergence of a paroxysmal nocturnal hemoglobinuria clone in aplastic anemia.

The newly described monoclonal antibody By114 has been used with flow cytometry to investigate the status of the 90-kD glycosylphosphatidyl-inositol (GPI)-anchored component of CD66 (CD66c) on neutrophils from nine patients with paroxysmal nocturnal hemoglobinuria (PNH), seven with aplastic anemia/PNH, and 63 with aplastic anemia (AA) and a negative Ham's test. We have found that By114 is a sensitive indicator for recognizing patients with PNH and has helped delineate a group of nine patients with aplastic anemia and a negative Ham's test who have evidence of a larger PNH clone than indicated by other monoclonal antibodies (mAbs). By114 is a valuable marker for detecting the emergence of a PNH clone before the Ham's test becomes positive and is a more sensitive detector of deficient GPI-anchored proteins than other mAbs.

Increased apoptosis in aplastic anemia bone marrow progenitor cells: possible pathophysiologic significance.

We have quantitated apoptotic cells by flow cytometry in human bone marrow (BM) and peripheral blood (PB) from normal donors and aplastic anemia (AA) patients, using the fluorescent DNA-binding dye 7-amino actinomycin D (7AAD). No significant difference was found in baseline percent apoptosis between normal and AA samples. Serum deprivation induced cell death to a greater degree in AA samples than in normal samples, but this was not significant. Using dual staining with anti CD34 antibody and 7AAD, we have shown that CD34+ progenitors in normal PB are significantly more apoptotic than those in normal BM. AA BM CD34+ cells contain a significantly greater proportion of apoptotic cells than normal BM CD34+ cells. Those AA patients with the lowest absolute number of CD34+ cells showed the highest proportion of apoptotic CD34+ cells. This appears to be related to clinical severity (transfusion dependence) at the time of study. We conclude that apoptosis is accelerated in AA BM progenitors and that this may contribute to the stem cell deficiency characteristic of this disorder.

In vitro response of normal and aplastic anemia bone marrow to mast cell growth factor and in combination with granulocyte-macrophage colony-stimulating factor and interleukin-3.

We have examined the effect of mast cell growth factor (MGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3), singly or in combination, on the growth of normal and aplastic anemia (AA) bone marrow in clonogenic assay and long-term bone marrow culture (LTBMC). MGF stimulated colony-forming unit-granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and mixed colony-forming unit (consisting of granulocyte-macrophage and erythroid elements) (CFU-GEM) colony formation from both normal and AA marrow. The three-factor combination stimulated the greatest number of colonies. Marrow from less severely affected AA patients was stimulated to produce the highest number of colonies, and a normal response was possible if progenitors were present. When added to LTBMC, MGF alone had little effect. GM-CSF and IL-3 stimulated increased numbers of progenitor cells harvested each week from normal and AA LTBMC. This resulted in normal colony numbers in some patients, the majority of whom were less severely affected than the patients who did not respond in LTBMC. The three-factor combination was additive for normal CFU-GM production. However, no further increases in AA LTBMC resulted from the addition of MGF to GM-CSF and IL-3. The partial correction in clonogenic assay with MGF in some AA patients raises the possibility of therapeutic benefit. We failed to demonstrate increased progenitor cell numbers in AA LTBMC, however. Further studies may overcome possible limitations to progenitor cell proliferation.

Mechanism of suppression of normal hemopoietic activity by lymphokine-activated killer cells and their products.

Interleukin 2 (IL-2)-activated lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to inhibit the formation of autologous human granulocyte-macrophage hemopoietic progenitors (granulocyte-macrophage colony-forming units, CFU-GM) in vitro. Effects of LAK cells on these progenitors may include a number of different mechanisms. LAK cells are potent cytotoxic lymphocytes capable of lysing certain normal autologous cells. They also produce cytokines known to inhibit hemopoiesis (interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]) or enhance it (granulocyte-macrophage colony-stimulating factor, GM-CSF). In our current study we analyzed the mechanism of suppression of autologous CFU-GM by LAK cells. Our results suggest that LAK cells are not directly cytotoxic to normal CFU-GM. We show that it is possible to abolish the hemopoiesis-inhibiting activity of LAK cells without abrogating their cytotoxicity against tumor cell lines using inhibitors of DNA synthesis, namely hydroxyurea or irradiation.

Separation of human blast progenitors from granulocytic, erythroid, megakaryocytic, and mixed colony-forming cells by "panning" on cultured marrow-derived stromal layers.

Primitive myeloid progenitor cells will adhere to stromal feeder layers of human bone-marrow-derived adherent cells grown in the presence of methylprednisolone (MP+ layers). These progenitors form colonies of blast cells on the MP+ stromal layers, but not on stromal layers grown in the absence of MP (MP- layers). The present study was designed to determine whether this failure of colony formation was caused by inability of the progenitors to adhere to the MP- layers or inability to proliferate in their presence. We also compared the capacities of the blast progenitors to adhere to MP+ and MP- stromal cells with those of mixed (GEMM-CFC), erythroid (BFU-E), megakaryocytic (Mk-CFC), and granulocyte-macrophage (GM-CFC) colony-forming cells. Incubation of bone marrow mononuclear cells with MP+ stromal layers removed 90% of the blast progenitors, but did not remove the majority of the GEMM-CFC, BFU-E, Mk-CFC, and GM-CFC; incubation of bone marrow mononuclear cells with MP- stromal layers did not remove the blast progenitors or the GEMM-CFC, BFU-E, Mk-CFC, and GM-CFC. Thus, the blast progenitors adhere to MP+ stromal feeder layers, but not to MP- stromal layers. In this respect they differ from the other more mature colony-forming cells that do not show any marked tendency to adhere to either type of stromal layer.