Study of KDM1A and VEGF changes as the responsible genes in the angiogenesis of breast cancer.

BACKGROUND: Recent developments regarding the contribution of microRNAs to tumor angiogenesis and the oncogenic effects of microRNAs point to their potential role in breast cancer angiogenesis. Tumor-derived exosomes are considered a rich source of microRNAs that can regulate the function of other cells in the tumor microenvironment, including vascular endothelial cells. This study analyzes the effect of tamoxifen chemotherapy on the expression of a key microRNA, miR-329, and introduces a regulatory link between this microRNA and the KDM1A gene associated with the vascular endothelial growth factor (VEGF) messaging pathway. MATERIALS AND METHODS: MCF-7 breast cancer cells were purchased and cultured in a complete culture medium. These cells were treated with tamoxifen and then their exosomes were extracted from the culture medium. The RNAs of the exosomes were isolated and the expression of miR-329, VEGF, and KDM1A genes in the exosomes was investigated using the real-time polymerase chain reaction (PCR) method. RESULTS: The results of this study showed that tamoxifen treatment increased the expression of miR-329 in exosomes derived from MCF-7 cancer cells. The expression of KDM1A and VEGF genes in drug-treated cell exosomes is downregulated. CONCLUSION: The results of this experiment demonstrated that the treatment of breast cancer cells with tamoxifen reduces the expression of VEGF and KDM1A by increasing miR-329. The treatment therefore reduces angiogenesis, and thus its anti-tumor effects are applied.

Reconstruction and analysis of circRNA-miRNA-mRNA network in the pathology of lung cancer.

BACKGROUND: The presented study aimed to gain insights into the pathogenesis of lung cancer (LC) and provide novel bio-markers for LC by building a regulatory circular (circ) RNAmicro (mi) RNAmRNA network. MATERIALS AND METHODS: High-throughput sequencing data of circRNAs, miRNAs and mRNAs related to LC originated from GEO (Gene Expression Omnibus) database, and the differential expressions of circRNAs, miRNAs and mRNAs were screened with R language Limma. The circRNA-miRNA and miRNA-mRNA pairs were used to build the ceRNA network. The functions of differential expression circRNAs were elucidated by performing the functional enrichment analysis on GO and KEGG. Furthermore, the selected LC prognostic genes were verified by tissue chips and immunohistochemistry (IHC). RESULTS: On the whole, 20 downregulated circRNAs, 55 upregulated miRNAs and 243 downregulated mRNAs were identified in LC. Lastly, a circRNA-miRNA-mRNA ceRNA network was built, which was composed of 2 circRNAs, 2 miRNAs, and 2 mRNAs. As indicated from the analysis based on public databases and IHC, the differential genes (i.e., FXYD1 and SEMA5A) in this network acted as LC prognostic factors. As confirmed by performing IHC and survival analyses, FXYD1 and SEMA5A expressions in LC were downregulated, and their expressions displayed a relationship to the overall survival (OS) of LC cases. CONCLUSIONS: This study presents novel insights into the role of circRNAs in the development of LC via the ceRNA mechanism. The identified FXYD1 and SEMA5A gene could act as novel and vital LC prognostic indicators.

Development of a conversion model between mechanical and electrical vestibular stimuli.

The vestibular end-organs encode for linear and angular head accelerations in space contributing to our internal representation of self-motion. Activation of the vestibular system with transmastoid electrical current has recently grown in popularity; however, a direct relationship between electrically evoked and mechanically evoked vestibular responses remains elusive in humans. We have developed and tested a mechanical-to-electrical vestibular stimulus conversion model incorporating physiological activation of primary vestibular afferents identified in nonhuman primates. We compared ocular torsional responses between mechanical (chair rotation) and model-derived electrical (binaural-bipolar) stimuli in separate experiments for an angular velocity step change (±10 deg/s over 1 s, ±4-mA peak amplitude; n = 10) and multisine angular velocities (±10 deg/s, 9.7 mA peak to peak, 0.05-1 Hz; n = 5), respectively. Perception of whole body rotation (n = 18) to our step-change stimuli was also evaluated. Ocular torsional slow-phase velocity responses between stimulation types were similar (paired two one-sided tests of equivalence: multiple P < 0.002; one-sample t test: P = 0.178) and correlated (Pearson's coefficient: multiple P < 0.001). Bootstrap analysis of perceived angular velocity likewise showed similarity in perceptual decay dynamics. These data suggest that central processing between stimuli was similar, and our vestibular stimulus conversion model with a conversion factor of ∼0.4 mA per deg/s for an angular velocity step change can generate electrical stimuli that replicates dynamic vestibular activation elicited by mechanical whole body rotations. This proposed vestibular conversion model represents an initial framework for using electrical stimuli to generate mechanically equivalent activation of primary vestibular afferents for use in biomedical applications and immersive reality technologies.NEW & NOTEWORTHY With the growing popularity of electrical vestibular stimulation in biomedical and immersive reality applications, a direct conversion model between electrical and mechanical vestibular stimuli is needed. We developed a model to generate electrical stimuli mimicking the physiological activation of vestibular afferents evoked by mechanical rotations. Ocular and perceptual responses evoked by mechanical and model-derived electrical stimuli were similar, thus providing a critical first step toward generation of electrically induced vestibular responses that have a realistic mechanical equivalent.

The relationship between cultural capital and lifestyle health behaviours in young people: a systematic review.

OBJECTIVES: While the universal prevalence of unhealthy lifestyle behaviours is high, cultural capital as a non-material resource shaping individuals' tastes can provide a substantial insight into different lifestyle behaviour choices. The aim of the present systematic review was to examine the evidence on the association between the three forms of cultural capital and lifestyle health behaviours. STUDY DESIGN: This is a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality appraisal was carried out using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (QAT-OCCSS). METHODS: The review included searches of 13 electronic databases with no restriction on the year of publication. Data were extracted using inclusion criteria and analysed using a narrative format. Eighteen studies were eligible for inclusion. RESULTS: The relationship between cultural capital and lifestyle behaviours was confirmed in the studies measuring institutionalised cultural capital, and mostly supported in the studies that measured objectified and embodied cultural capital. While cultural capital had a significant relationship with some lifestyle behaviours, it was not significantly related to others. The important methodological weaknesses in the literature preclude the ability to state the associations as unequivocal. CONCLUSION: While the association between cultural capital and lifestyle behaviours was supported in most of the included studies, more rigorous research methods are required to effectively assess the causality between cultural capital and lifestyle behaviours. More precise findings may lead to new entry points for the development of interventions to promote healthy lifestyle behaviours.

Analysis of the cox1 gene in Echinococcus granulosus from sheep in northeast Iran using PCR high-resolution melting (qPCR-HRM) curve analysis.

Echinococcus granulosus, the etiologic agent of echinococcosis, is one of the most important zoonotic helminthes worldwide. Knowledge of E. granulosus species and genotypes has important implications for epidemiology, control, and prevention of diseases as well as future vaccine and drug designs. There are many molecular methods developed to define genotypes of E. granulosus, among them high resolution melting (HRM) analysis, as a new approach, is a single step and closed tube method. It is appropriate for fast screening of large number of isolates. This technique is an accurate, user friendly, cost-effective, fast and simple method, which does not need post-PCR processes. Between March and lst august 2016, of 726 sheep examined in abattoirs in Razavi Khorasan province, Northeast Iran, 109 harboured cystic echincoccosis lesions (liver samples= 65 and lung samples= 44) which were collected for analysis. Total genomic DNA was extracted from each sample and amplified for the presence of polymorphism in the mitochondrial cox1 gene of Echinococcus granulosus using a high resolution melting curve (HRM) method. A total of 109 hydatid cyst samples analyzed by PCR high-resolution melting (qPCR-HRM) curve of the cox1 gene, all isolates were identified as G1 genotype (sheep strain). G1 is the predominant genotype in sheep in northeast of Iran. The high incidence of the G1 genotype (known to be the predominant E. granulosus genotype infecting humans globally) in sheep has considerable implications for hydatid disease control programs in this area.

Evaluation of a novel lentiviral vaccine expressing KMP11-HASPB fusion protein against Leishmania infantum in BALB/c mice.

Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania protein against which antibodies are produced in the sera of cutaneous and visceral Leishmaniasis (VL) patients. Kinetoplastid membrane protein 11 (KMP11) is another protein antigen of Leishmania which is reported as a promising candidate for vaccination of VL. It is a highly conserved surface protein present in all members of kinetoplastid family and is expressed in both promastigotes and amastigotes. In this study, the coding sequence of KMP11 and HASPB was cloned into a pCDH-cGFP lentiviral vector as a fusion protein. The gene expression was confirmed using RT-PCR and Western blot methods. After injection of the recombinant KMP11-HASPB-expressing lentiviruses to BALB/c mice, using ELISA technique, a significant increase in IFN-γ and IL-4 as well as IgG1 and IgG2a was observed compared to the control group. Furthermore, the number of parasites in the liver and spleen of vaccinated mice decreased significantly compared with the control group.

PCR-RFLP diagnosis and characterization of Leishmania species causing human cutaneous leishmaniasis and evaluation of treatment times with glucantime in these patients.

Antimony compounds are first line treatments for cutaneous leishmaniasis. The prognosis of the disease varies depending on the type of medicine and species. We aimed to determine the species responsible for cutaneous leishmaniasis in patients referred to Skin Diseases and Leishmaniasis Research Center in Isfahan and Bam Health Center (Kerman) in order to follow and assess the complete healing of the lesions. A total of 40 skin lesions samples were collected from patients with cutaneous leishmaniasis (CL) form January 2014 to 2015. Dermal scrapings were analyzed by examination of Giemsa-stained smears. Parasites were cultured and isolated in NNN and RPMI 1640 medium and DNA was extracted. We used PCR-RFLP assays of ITS1 genes for direct identification of Leishmania species. Treatment process was assessed after a treatment period with glucantime and healing of the studied cases was followed up. All the samples from Isfahan and Bam regions were L. major and L. tropica species respectively. In patients infected with L. major and L. tropica treated with glucantime, the shortest healing period was 40 days in 5(25%) and 60 days in 3(15.8%) patients, respectively and the longest healing period was 100 days in 1 (5%) and 160 days in 1 (5.3%) patient, respectively. The mean complete healing periods in patients with L. tropica and L. major were 100 and 58 days, respectively (P<0.001). Average recovery period for people with dry cutaneous leishmaniasis is longer than average recovery period for people with wet cutaeous leishmaniasis.

Reform in medical and health sciences educational system: a Delphi study of faculty members' views at Shiraz University of Medical Sciences.

Despite the strengths in the Iranian medical and health sciences educational system, areas in need of improvement have been noted. The purpose of this study was to understand the views of faculty members at Shiraz University of Medical Sciences about current and future needs for medical and health sciences education, with the goal of improving the quality of the educational system. The data were collected using a Delphi consensus method. Analysis of the findings identified the following key themes among the factors likely to contribute to medical and health sciences education and training: adding and/or increasing student numbers in higher degrees in preference to associate degrees; providing more interactive, student-centred teaching methods; improving the educational content with more practical and research-based courses tailored to society's needs; and an emphasis on outcome-based student evaluation techniques. These changes aim to respond to health trends in society and enhance the close relationship between medical education and the needs of the Iranian society.

Reform in medical and health sciences educational system:a Delphi study of faculty members' views at Shiraz University of Medical Sciences

Despite the strengths in the Iranian medical and health sciences educational system, areas in need of improvement have been noted.The purpose of this study was to understand the views of faculty members at Shiraz University of Medical Sciences about current and future needs for medical and health sciences education, with the goal of improving the quality of the educational system.The data were collected using a Delphi consensus method.Analysis of the findings identified the following key themes among the factors likely to contribute to medical and health sciences education and training:adding and/or increasing student numbers in higher degrees in preference to associate degrees; providing more interactive, student-centred teaching methods; improving the educational content with more practical and research-based courses tailored to society's needs; and an emphasis on outcome-based student evaluation techniques.These changes aim to respond to health trends in society and enhance the close relationship between medical education and the needs of the Iranian society

على الرغم من مواطن القوة في النظام التعليمي الإيراني للعلوم الصحية والطبية، فإن هناك مجالات يتعين تحسينها.وتهدف هذه الدراسة إلى فهم وجهات نظر أعضاء هيئة التدريس في جامعة شيراز للعلوم الطبية حول الاحتياجات الحالية والمستقبلية في التعليم الصحي والطبي، بهدف تحسين جودة النظام التعليمي. وقد جمع الباحثون البيانات بطريقة الإجماع دلفي. وحددت النتائج أن المواضيع الرئيسية التالية هي من بين العوامل التي يغلب أن تساهم في التعليم والتدريب في العلوم الصحية والطبية: إضافة أو زيادة أعداد الطلاب في الدرجات العالية لصالح الدرجات الإضافية، تقديم المزيد من طرق التعليم التفاعلية والمتمحورة حول الطلاب، تحسين المضمون التعليمي بإضافة دورات عملية تستند على البحوث ومصممة لتلبية احتياجات المجتمع، والتأكيد على تقنيات تقييم التلاميذ استنادا إلى النتائج. وتهدف هذه التغيرات للاستجابة للاتجاه الصحي السائد في المجتمع ولتعزيز العلاقة الصميمية بين التعليم الطبي وبين احتياجات المجتمع الإيراني

Malgré les aspects positifs du système iranien d'enseignement de la médecine et des sciences de la santé, certains domaines nécessitant une amélioration ont été identifiés.La présente étude visait à comprendre les points de vue des membres du corps enseignant de l'Université des Sciences médicales de Chiraz sur les besoins présents et à venir de l'enseignement de la médecine et des sciences de la santé, avec pour objectif d'améliorer la qualité du système d'enseignement.Les données ont été recueillies à l'aide de la méthode de consensus Delphi.L'analyse des résultats a permis de dégager les thèmes clés suivants parmi les facteurs susceptibles de contribuer à l'enseignement de la médecine et des sciences de la santé ainsi qu'à la formation en la matière:augmenter le nombre d'étudiants dans les années d'études supérieures plutôt dans que celles des diplômes d'études générales; proposer davantage de méthodes d'enseignement interactives et axées sur l'étudiant; améliorer le contenu de l'enseignement par des cours davantage centres sur la pratique et la recherche et adaptés aux besoins de la société; et privilégier les techniques d'évaluation de l'étudiant reposant sur les résultats.Ces changements visent à répondre aux tendances en matière de santé dans la société et à renforcer le lien étroit entre l'enseignement de la médecine et les besoins de la société iranienne

Cerebrospinal fluid ferritin in children with viral and bacterial meningitis.

Despite the fact that the prognosis of bacterial meningitis has been improved by the influence of antibiotics, this disease is still one of the significant causes of morbidity and mortality in children. Rapid differentiation between bacterial and aseptic meningitis, and the need for immediate antibiotic treatment in the former, is crucial in the prognosis of these patients. Ferritin is one of the most sensitive biochemical markers investigated in cerebrospinal fluid (CSF) for the early diagnosis of bacterial meningitis. The present study aims to evaluate the diagnostic capability of CSF ferritin in differentiating bacterial and viral meningitis in the paediatric setting. A cross-sectional study was carried out in the referral Children's Medical Center Hospital, Tehran, during 2008 and 2009. According to the inclusion criteria, CSF samples from 42 patients with suspected meningitis were obtained and divided into two meningitis groups, bacterial (n = 18) and viral (n = 24). Ferritin and other routine determinants (i.e., leucocytes, protein and glucose) were compared between the two groups. Ferritin concentration in the bacterial meningitis group was 106.39 +/- 86.96 ng/dL, which was considerably higher than in the viral meningitis group (10.17 +/- 14.09, P < 0.001). Mean CSF protein concentration and cell count were significantly higher in the bacterial meningitis group and showed a positive correlation with CSF ferritin. In conclusion, this study suggests that CSF ferritin concentration is an accurate test for the early differentiation of bacterial and aseptic meningitis; however, further investigation on a larger cohort of patients is required to confirm this finding.

Study of a nanoscale water cluster by atomic force microscopy.

We present a novel method for investigating a nanometric cluster of water molecules, which includes the formation and manipulation of nanometric water, and the measurement of its mechanical properties. The atomic force microscope based on the quartz tuning-fork sensor is employed to form and manipulate the nanometric water, and the theoretical tool of amplitude-modulation atomic force microscopy is used to obtain the elasticity, viscosity and dissipation energy of it. With high vertical resolution less than approximately 0.1 nm and high force sensitivity of approximately 0.01 N m(-1), this tool facilitates the stable formation and manipulation of a nano-water cluster (approximately 10(4) molecules) in air without 'jump-to-contact' instability, as well as quantitative measurements of its physico-chemical properties. PACS numbers: 47.55.nk, 62.10.+s, 68.37.Ps

Comparison of the effect of amniotic membrane suspension and autologous serum on alkaline corneal epithelial wound healing in the rabbit model.

PURPOSE: Alkaline corneal epithelial wound closure rates in rabbit eyes were compared after topical applications of amniotic membrane suspension, autologous serum, or preservative-free artificial tears. METHODS: Thirty rabbits were divided into 3 randomization groups of 10 rabbits each. Central corneal alkali wound was produced in both eyes of the rabbits by applying a 5-mm round filter paper, soaked in 1 N NaOH, for 60 seconds. Group 1 animals received preservative-free artificial tears in 1 eye and amniotic membrane suspension in the other eye; group 2 animals received preservative-free artificial tears in 1 eye and autologous serum in the other eye; and group 3 animals received autologous serum in 1 eye and amniotic membrane suspension in the other eye. The treatment was dosed 4 times a day with the eyedrops, and epithelial wound closure was recorded using slit lamp. The data were analyzed to determine the rate of wound closure. RESULTS: The mean wound radius closure rate was 67.8 +/- 5.2 microm/h for autologous serum-treated eyes, 74.5 +/- 5.4 microm/h for amniotic membrane suspension-treated eyes, and 66.8 +/- 5.0 microm/h for preservative-free artificial tear-treated eyes. CONCLUSIONS: This study shows that alkali-injured corneal epithelial wounds heal faster when treated with amniotic membrane suspension than with autologous serum or preservative-free artificial tears.

Restoration of morphine-induced alterations in rat submandibular gland function by N-methyl-D-aspartate agonist.

The effects of morphine, 1-aminocyclobutane-cis-1,3-dicarboxylic (ACBD; NMDA agonist) and 3-((R)2-carboxypiperazin-4-yl)-propyl-l-phosphoric acid (CPP; NMDA antagonist) and their concurrent therapy on rat submandibular secretory function were studied. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Intraperitoneal injection of morphine (6 mg/kg) induced significant inhibition of salivary flow rate, total protein, calcium, and TGF-beta1 concentrations. Administration of ACBD (10 mg/kg) and CPP (10 mg/kg) alone did not influence secretion of submandibular glands. In combination therapy, coadministration of CPP with morphine did not influence morphine-induced changes in salivary function while ABCD could restore all morphine-induced changes. In combination treatment, ACBD prevented morphine-induced reduction of flow rate, total protein, calcium, and TGF-beta1 and reached control levels. It is concluded that morphine-induced alterations in submandibular gland function are mediated through NMDA receptors.

Prevalence of work-related respiratory symptoms in Iranian farmers.

BACKGROUND: Animal exposure may be an important trigger for work-related symptoms among farmers. OBJECTIVE: To estimate the prevalence of work-related respiratory symptoms (WRS) in sheep breeders and agricultural farmers and to determine work-related risk factors. METHODS: A family doctor used a questionnaire to interview a cohort of 173 farmers comprised of 127 sheep breeders and 46 agricultural farmers in the rural area of Rokh (northeast Iran). The questionnaire pertained to recurrent wheezing, cough, breathlessness or chronic phlegm while at work (these symptoms define WRS), flu-like illness and physician-diagnosed asthma. RESULTS: There were 71 subjects (41%) with WRS: 10 of 46 agricultural farmers (21.7%) and 61 of 127 sheep breeders (48.0%). The proportions of sheep breeders with wheezing (16.5%), asthma (14%), cough (29%), breathlessness (31.5%) and flu-like illness (38%) were higher than in agricultural farmers. A significant dose-response relationship among the daily hours worked with animals, the number of animals and the prevalence of symptoms was established for sheep farmers. Sheep shearing and the use of pesticide were associated with an increased risk of wheezing and phlegm. CONCLUSIONS: The results suggest that sheep farmers in general have higher rates of work-related symptoms than agricultural farmers. The severity of work-related symptoms will increase with an increase in frequency of animal contact; therefore, these results may underestimate the impact of this exposure.

Manometric evaluation of achalasia in the elderly.

BACKGROUND: The effect of ageing on oesophageal motility in patients with achalasia is not well described. Oesophageal contraction amplitude is decreased in otherwise healthy elderly subjects. AIM: To evaluate whether ageing influences the motor function of the oesophagus in achalasia. METHODS: Initial manometry studies of patients with achalasia were reviewed and findings (lower oesophageal sphincter basal and residual pressures and oesophageal body contraction amplitudes) were compared between two groups of patients, those 65 years of age or older (49 patients) and those younger than 65 years (68 patients). The older group was further divided into those > or =70 years and those <70 years. RESULTS: Patients 65 years and older had significantly higher lower oesophageal sphincter basal pressures compared with younger patients (65.6 +/- 4.9 vs. 52.3 +/- 2.7, P = 0.02). At an age cut-off of 70 years, older patients had significantly higher basal (70.7 +/- 1.6 vs. 53.0 +/- 2.4, P = 0.02) and residual (19.7 +/- 1.6 vs. 15.9 +/- 0.7, P = 0.03) lower oesophageal sphincter pressures compared with younger patients. Amplitude of oesophageal contractions was not different between the groups. Across all age groups, there was no linear correlation between age and basal or residual lower oesophageal sphincter pressures (r = 0.28 and 0.12, respectively). CONCLUSIONS: Older patients with achalasia have higher lower oesophageal sphincter pressures, however there is no linear correlation between age and lower oesophageal sphincter pressures. Unlike healthy subjects, advanced age is not associated with a decrease in oesophageal contraction amplitude in patients with achalasia.

Supplementation of urban home visitation with a series of group meetings for parents and infants: results of a "real-world" randomized, controlled trial.

OBJECTIVE: Home visitation has been shown to be effective in reducing rates of child maltreatment and in enhancing psychosocial outcomes in children and their parents. Even when available, however, it is underutilized by parents in some urban settings. We tested a supplemental 10-session group intervention for its ability to increase active participation in home visitation, enhance the quality of caregiving behavior of parents, and improve social developmental outcome in children. METHOD: A randomized controlled design was utilized, involving two separate cohorts of parents of 3- to 18-month old infants, totaling 148 parent-child dyads. The intervention focused on practical experience in promoting parent-infant attachment relationships. RESULTS: At 6 months follow-up, there was a substantial increase in the proportion of intervention group parents participating in home visitation, compared to parents in the control group (Fisher's exact p = .008). Parents in the intervention group exhibited a trend for improvement in their capacity to appropriately interpret infants' emotional cues (p = .08), independent of the effects of home visitation itself. Attrition in both the treatment and control groups was inversely associated with income and level of education. CONCLUSIONS: Group meetings may constitute an effective means of engaging stressed urban families in home visitation.

Comparison of glucocorticoid-induced effects in prolactin-dependent and autonomous rat Nb2 lymphoma cells.

Cultured Nb2 node rat lymphoma cells require lactogenic hormone for their proliferation. We reported previously that dexamethasone (Dex) inhibits prolactin (PRL)-induced mitogenesis and, in the absence of mitogen, induces apoptosis of Nb2 cells. Both antiproliferative and cytolytic effects of Dex on Nb2 cells appear to involve glucocorticoid (Type II) receptor mediation. In this study, we compared Dex effects in PRL-dependent Nb2 cells (Nb2) with SFJCD1 (SF), a clone of Nb2 cells that proliferates independently of exogenous PRL. Proliferative assays involved a 72-hr incubation in a chemically defined, serum-free medium where ovine PRL (1 ng/ml) was added to Nb2 cells but not to SF cells. Both cell lines were responsive to the antiproliferative effects of Dex in a dose (6.25-200 nM)-dependent fashion of comparable sensitivity and magnitude. Co-incubation with the glucocorticoid receptor antagonist, RU 486, prevented the antiproliferative effect of Dex in both cell lines. In the same medium devoid of PRL, Dex was cytolytic to Nb2 cells and fragmented DNA in a fashion reflective of apoptosis, but was ineffective in SF cells. A dual chamber incubation system revealed no evidence that SF cells produced cytokines that were mitogenic or anticytolytic to Nb2 cells. Both Nb2 and SF cells fragmented DNA in a fashion indicative of apoptosis in the presence of the Ca2+ ionophore, A23187 (1 microM). These studies reveal a basic difference in glucocorticoid responsiveness between the PRL-dependent Nb2 cell line and its PRL-independent subclone, SF. While both cell lines exhibit functional glucocorticoid receptors and the necessary intranuclear machinery for apoptosis, the pathway mediating the latter is inhibited or dysfunctional in SF cells.