Sinonasal involvement in sarcoidosis: a report of seven cases and review of literature.

Sarcoidosis is a chronic systemic disease of unknown etiology characterized by non-caseating inflammation involving one or more organs with predilection for pulmonary and upper respiratory tract involvement. It presents with a variety of signs and symptoms which can be generalized or focused on a single organ. Sinonasal involvement is reported in about 1% of cases of sarcoidosis. Sarcoidosis can involve both the mucosa as well as bony structures in the nose and the paranasal sinuses. We present seven cases of sarcoidosis with sinonasal involvement. Four cases presented with nasal and sinus symptoms, and the other three cases developed or presented with nasal and sinus symptoms after the diagnosis of sarcoidosis was confirmed. The nasal and sinus symptoms in these patients were managed by local and systemic steroids. In four patients, endoscopic sinus surgery was performed with good outcome. Nasal and sinus symptoms, differential diagnosis and the treatment are discussed.

Health-related quality of life scores in long-term head and neck cancer survivors predict subsequent survival: a prospective cohort study.

OBJECTIVE: To examine the survival prediction of long-term health-related quality of life in patients with head and neck squamous cell carcinoma. DESIGN: Patients with head and neck squamous cell carcinoma diagnosed in the period between July 1992 and October 2001, who had been disease free for a minimum of 1 year following therapy, responded to structured interviews including several validated questionnaires in the period from October 2002 to March 2004. The study ended in June 2009 with a mean observation time of 75 ± 4 months among the survivors. Twenty-four deaths were observed. SETTING: University hospital, referral centre of the Western Norway. PARTICIPANTS: One hundred and thirty-nine cognitive functioning patients. MAIN OUTCOME MEASUREMENTS: Overall survival as of June 2009. This was correlated with various clinical factors and the EORTC QLQ-C30 questionnaire, the Eysenck Personality Inventory and the Coping inventory completed between October 2001 and March 2004. RESULTS: A general symptom sum score was significantly predictive of survival directly and after sequential adjustment for self-reported levels of neuroticism, avoidance focused coping, coping by suppression of competing activity, alcohol consumption, smoking status and heart/lung disease, as well as gender, age, time between diagnosis and inclusion, tumour node metastasis (TNM) stage and tumour site. Similar results were found for the health-related quality of life indices 'fatigue', 'dyspnoea' and 'sleep disturbance'. A dichotomised variable based on the general symptom sum score was calculated, and a high risk group, as to mortality, including less than a quintile of the total patient population was established. A hazard ratio of 5.15 was found for the dichotomised general symptom sum score. CONCLUSION: We have shown a unique and independent survival prediction from long-term EORTC QLQ-C30 scores in successfully treated and cognitive functioning head and neck squamous cell carcinoma patients.

MAPKs ERK and p38, but not JNK phosphorylation, modulate IL-6 and TNF-α secretion following OK-432 in vitro stimulation of purified human monocytes.

Interaction between the immune system and cancer allows for the use of biological response modifiers, e.g. OK-432, in cancer therapy. OK-432, penicillin-killed Streptococcus pyogenes, is used in treating carcinomas, but also lymphangiomas. We have studied the role of monocytes (MOs) in the immune response to OK-432 by examining IL-6 and tumour necrosis factor (TNF)-α secretion after in vitro MO stimulation with OK-432, to some extent in comparison with lipoteichoic acid (LTA) and lipopolysaccharide (LPS). LTA stimulation of whole blood gave IL-6 but not TNF-α secretion, as previously shown with OK-432 stimulation, whereas both cytokines were secreted following LPS stimulation. Addition of the MAPK kinase (MAPKK) MEK inhibitor U0126 inhibited IL-6/TNF-α secretion in a dose-dependent manner. Flow cytometry and to some extent Western blot (Wb) analyses showed that MAPK ERK, located downstream of MEK1/2, is predominantly phosphorylated at isolation from peripheral blood. Addition of the p38 MAP kinase inhibitor SB202190 decreased MO IL-6/TNF-α production upon OK-432 stimulation in a dose-dependent manner. Addition of the MAPK JNK inhibitor SP600125 did not systematically change the MO IL-6/TNF-α OK-432 response. Flow cytometry showed that when stimulating the MOs before isolation from blood, LPS yielded ERK phosphorylation and LPS/LTA p38 phosphorylation, whereas OK-432 had no effects on phosphorylation levels. In conclusion, we have shown that OK-432 resembles TLR2 more than TLR4 stimulation of MOs and depends on MAPKK MEK and MAPK p38, but not on JNK phosphorylation. The MEK and p38 MO OK-432 stimulation dependence is possibly related to the differentiation of cells of the MO lineage.

Co-culture of head and neck squamous cell carcinoma spheroids with autologous monocytes predicts prognosis.

Co-culture of monocytes with autologous fragment (F) spheroids originating from malignant (M) tumour or benign (B) control mucosa of head and neck squamous cell carcinoma (HNSCC) yields interleukin (IL)-6 and monocyte chemo-attractant protein (MCP)-1 secretion. This study investigates the association between this cytokine co-culture response and prognosis. Analysis of IL-6 and MCP-1 content of supernatants from monocytes in vitro co-culture with autologous MF- or BF-spheroids was investigated in a cohort of HNSCC patients (n = 65) diagnosed between 1998 and 2005, all of whom were treated with curative intent by primary surgery. The IL-6 response was expressed as a fraction of the lipopolysaccharid response of the same batch of monocytes. Recurrence, survival and causes of death were then established following the second part of 2005. MCP-1 levels did not predict prognosis. We found that increased levels of IL-6 from autologous monocytes in co-culture with MF-spheroids predicted recurrence with a hazard ratio (HR) of 1.5 [confidence interval (CI): 1.01-2.60; P = 0.05] and co-culture with BF-spheroids and monocytes predicted recurrence (HR = 4.17; CI: 1.54-11.29; P = 0.005). The same results where obtained in addition with TNM stage of the patients. Simultaneous analysis of BF- and MF-spheroid co-culture IL-6 responses as well as adjustment for age and TNM stage of the patients allowed prediction of total survival (HR = 3.1; CI: 1.11-8.56; P = 0.03) based on BF co-culture levels. IL-6 secreted upon in vitro co-culture with monocytes and BF-spheroids predicts recurrence and prognosis, whereas co-culture with monocytes and MF-spheroids predicts recurrence.

TNF-alpha is secreted by monocytes in transit to become macrophages, but not by peripheral blood monocytes, following OK-432 (lyophilized S. pyogenes) stimulation.

OK-432, penicillin-killed Streptococcus pyogenes, is used in treating lymphangiomas and carcinomas. We have studied proinflammatory interleukin (IL) secretion following OK-432 stimulation of total blood, peripheral blood mononuclear cell (PBMC) and purified monocytes in vitro. OK-432 stimulation of purified monocytes gave IL-1beta, IL-1RA, IL-6, IL-12p40 and tumour necrosis factor (TNF)-alpha response. OK-432 stimulation of cells within blood did, however, not yield TNF-alpha secretion. When PBMC or monocytes were cultured in low-attachment wells a decreased IL secretion was observed compared to adherent cells. Inhibition of Syk kinase with piceatannol, only at high, non-specific doses, but not PI3 kinase inhibition with LY294002 or Wortmannin, decreased monocyte IL response to OK-432. This shows that beta(1-3)-integrin receptor function is not necessary for monocyte OK-432-stimulated TNF-alpha secretion. Direct blockage of the beta(2)-integrin (CD18) receptor by anti-CD18 antibody was also unable to prevent the stimulating effects of OK-432 in human monocytes. On the other hand, Syk phosphorylation is elevated upon adherence of monocytes and this is further increased by OK-432 stimulation, as shown by Western blot. The Fc-receptor was also ruled out as a main receptor of the OK-432 monocyte response. In conclusion, TNF-alpha secretion is only found in monocytes removed from blood. This TNF-alpha secretion is not mediated through the beta(1-3)-integrin receptors. OK-432 may act as a target-seeking substance whereby only monocytes adhered, e.g. to a tumour cell, become cytotoxic in part explaining why OK-432 is well suited as a cancer treatment drug.

Modelling lateral beam quality variations in pencil kernel based photon dose calculations.

Standard treatment machines for external radiotherapy are designed to yield flat dose distributions at a representative treatment depth. The common method to reach this goal is to use a flattening filter to decrease the fluence in the centre of the beam. A side effect of this filtering is that the average energy of the beam is generally lower at a distance from the central axis, a phenomenon commonly referred to as off-axis softening. The off-axis softening results in a relative change in beam quality that is almost independent of machine brand and model. Central axis dose calculations using pencil beam kernels show no drastic loss in accuracy when the off-axis beam quality variations are neglected. However, for dose calculated at off-axis positions the effect should be considered, otherwise errors of several per cent can be introduced. This work proposes a method to explicitly include the effect of off-axis softening in pencil kernel based photon dose calculations for arbitrary positions in a radiation field. Variations of pencil kernel values are modelled through a generic relation between half value layer (HVL) thickness and off-axis position for standard treatment machines. The pencil kernel integration for dose calculation is performed through sampling of energy fluence and beam quality in sectors of concentric circles around the calculation point. The method is fully based on generic data and therefore does not require any specific measurements for characterization of the off-axis softening effect, provided that the machine performance is in agreement with the assumed HVL variations. The model is verified versus profile measurements at different depths and through a model self-consistency check, using the dose calculation model to estimate HVL values at off-axis positions. A comparison between calculated and measured profiles at different depths showed a maximum relative error of 4% without explicit modelling of off-axis softening. The maximum relative error was reduced to 1% when the off-axis softening was accounted for in the calculations.

Obstructive jaundice due to isolated tuberculosis of the pancreas: endoscopic treatment instead of surgery?

The optimal treatment for relieving biliary obstruction due to isolated pancreatic tuberculosis has not so far been defined, and most previously reported patients were treated surgically. We describe a 17-year-old, immunocompetent girl who was admitted with obstructive jaundice caused by a tuberculous mass in the head of the pancreas. Antituberculous therapy alone failed to alleviate the jaundice, and she was therefore treated by stent insertion and, subsequently, balloon dilation of the common bile duct stricture. At follow-up 5 years later, magnetic resonance cholangiopancreatography showed no evidence of stricture in the common bile duct.

The amount of treatment versus quality of life in patients formerly treated for head and neck squamous cell carcinomas.

The aim of the present study was to investigate the association between the self-reported quality of life (QoL) versus the initial TNM stage and amount of primary and recurrent tumor therapy given in a population of formerly treated head and neck squamous cell carcinoma (HNSCC) patients. We determined QoL by the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ) C30/H&N35 by structured interview. One hundred and twenty-two patients less than 80 years old, who had been diagnosed with HNSCC in western Norway in the period from 1992 to1997, and who had survived until 2000, were identified. Of these patients, 106 were eligible to be included. Ninety-six of these patients agreed to be interviewed. For TNM stage as well as the type of therapy given (local surgery, neck dissection or radiation therapy), T stage predicted the general QoL scores. Both increased TNM stage and all given tumor therapy seemingly caused lower H&N symptom QoL scores. Of the various tumor treatments employed, neck radiation therapy and neck dissection were indicated to be the most closely associated with the H&N QoL scores. Having neck dissection performed seemingly caused impairment beyond what was explained by the initial TNM stage. In conclusion, tumor therapy to HNSCC should not be restricted due to general QoL considerations. Further study of how and when to perform neck treatment is suggested in order to avoid unnecessary reduced H&N QoL.

Psychological coping style versus disease extent, tumour treatment and quality of life in successfully treated head and neck squamous cell carcinoma patients.

OBJECTIVES: To study self-reported coping style by the COPE questionnaire and the association to tumour node distant metastasis (TNM) stage, received treatment and health-related quality of life (HRQoL) in a population of successfully treated head and neck squamous cell carcinoma (HNSCC) patients. DESIGN: Disease free HNSCC patients were interviewed during a regular outpatient visit to the Department. SETTING: All patients <80 years who had been diagnosed with HNSCC, in Western Norway, in the period from 1992 to 1997 and who were disease free in the year 2000 were included. MAIN OUTCOME MEASURES: The HNSCC patients were studied by the European organization for research and treatment of cancer quality of life (QoL) questionnaire and by the COPE questionnaire from which coping styles profiles were extracted. Clinical and socio-demographic variables were also gathered. RESULTS: Level of problem focused coping style was associated with the T stage and whether or not the patient was given neck radiotherapy. An avoidance-focused coping style was generally associated with lowered HRQoL. Employment of emotional focused coping was associated with low HRQoL among the patients treated with surgery only, and associated with increased HRQoL among patients treated with radiation therapy only. The associations between HRQoL and coping style levels were stronger for HRQoL indexes reflecting cognitive/emotional function than for HRQoL indexes reflecting physical function. CONCLUSIONS: In former HNSCC patients, level of problem focused coping style was associated with the T stage and if given neck radiotherapy. Level of avoidance coping was inversely associated with the HRQoL, and level of emotional coping was associated with HRQoL in a complex manner.

p53, Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma.

The prognosis in patients suffering from head and neck squamous cell carcinomas depends on many factors. However, regional lymph node metastases are the most important parameter in determining the cure and survival of patients with head and neck cancers. The evaluation of cancer cell biology enables differentiation of their proliferation and tendency of metastases. Immunohistochemical examinations complement the well-established routine histological examination. The aim of this study was to evaluate the prognostic importance of the level of immunoproliferating proteins such as cyclin D1, nuclear antigen Ki67 and suppressor gene p53 for regional lymph node metastases in laryngeal carcinoma. The research was carried out on 73 patients treated for squamous cancer of the larynx in the Department of Otolaryngology University School of Medical Sciences in Poznan in the years 1994-1999. The group was comprised of 4 female and 69 male patients. Their ages ranged from 37 to 79 years, with a mean of 59 years. Clinical data included sex, age, localization and local and regional extent of the tumor, presence or lack of distant metastases, treatment, histological examination as well as immunohistochemical evaluation of suppressor gene p53, proliferative proteins Ki67 and cyclin D1. No statistically significant correlation was found between staining intensity of suppressor gene p53, cyclin D1 and the degree of local advancement (T). There was no correlation between the level of immunoproliferative markers and regional lymph node metastases. Statistically significant correlation was found between T stage and staining for Ki67 (P=0.017) as well as between cyclin D1 level and Ki67 (P<0.05). In conclusion, (1) no significant correlation was found between Ki67 and cyclin D1, p53 and TNM classification; (2) lack of correlation was confirmed between N+, p53, Ki67, cyclin D1 and Jacobsson classification; (3) the degree of histological grading correlated, however, with Jacobsson classification and cyclin D1 expression.

The personality and quality of life in HNSCC patients following treatment.

The aim of the present study was to investigate the association between self-reported quality of life (QoL) and personality in successfully treated primary head and neck squamous cell carcinoma (HNSCC) patients. We determined QoL using the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ) C30/H and N35, and personality by the Eysenck Personality Inventory (EPI). All patients younger than 80 years who had been diagnosed with HNSCC in Western Norway in the period from 1992 to 1997, and who had survived until 1999, were sampled. 96 patients (a 90% response rate) were included. Questionnaires were also mailed to all Norwegian laryngectomised patients; 104 patients returned the questionnaires (a 50% response rate). The neuroticism scores were test re-test reliable as determined by the neuroticism scores measured at the primary HNSCC diagnosis for a sub-sample (N=22) of the included patients. High neuroticism was associated with a low QoL in both patient samples. The neuroticism score was associated with the QLQ-C30 scales (common variance: 17-25%) and all QoL scores in the laryngectomised group (common variance: 11-25%), and the H and N35 symptom scores in the laryngectomised sample. The associations could still be shown when adjustments were made for gender, age, marital status, educational level, number of children and level of treatment. Extraversion was associated with general QoL, physical and emotional scores in the HNSCC patient sample. Radiation therapy in the HNSCC sample was associated with the H and N35 symptom scores, but different ones to those associated with neuroticism. In conclusion, high neuroticism, but not extraversion, is associated with a lowered QoL.

Mechanisms for monocyte activation in co-culture with autologous tumor spheroids.

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro secrete interleukin (IL)-6 upon 24h in co-culture. Presently, the aim was to study the mechanisms of this monocyte secretion. Paraformaldehyde (0.1% for 2min) or actinomycin-D (1 microg/ml for 24h) pre-treatment of the F-spheroids abolished the monocyte IL-6 co-culture response. Addition of glucose (100mM) or mannose (100mM), and to some extent galactose (100mM), but not fructose (100mM) to the co-cultures, partly inhibited the monocyte IL-6 co-culture response, but such addition did not inhibit the in vitro monocyte lipopolysaccharide (LPS)-generated IL-6 secretion. When mannose was added to the co-cultures, monocyte IL-6 mRNA expression was eradicated in malignant co-cultures and reduced to a low level in benign co-cultures. Addition of mouse anti-human beta(1)-integrin (anti-CD29) antibody (2 microg/ml) diminished the IL-6 co-culture response but not the monocyte LPS-generated IL-6 response. In conclusion, the monocyte IL-6 co-culture response is dependent on live spheroids and to some extent on direct contact with the F-spheroids, possibly via lectin-like receptor(s), the mannose receptor and beta(1)-integrin.

The pattern of estradiol and progesterone differs in serum and tissue of benign and malignant ovarian tumors.

Epidemiological studies have indicated a relationship between gonadal steroid hormones and ovarian cancer. A production of both estradiol and progesterone by ovarian cancers has been demonstrated. The local steroid concentrations and the putative relation to histopathological and clinical condition were investigated herein. Ovarian tissue, ovarian tumor cyst fluid, ovarian vein samples and peripheral serum concentrations of estradiol and progesterone in pre- and post-menopausal women, subdivided into groups with normal ovaries, benign, borderline and malignant ovarian tumors, were quantitatively assessed. Both ovarian tissue concentrations of estradiol and progesterone were more than 100-fold higher than in serum. Based on differences in concentrations between different ovarian tumor groups, the data is not coherent with the previously suggested increased production of estradiol and progesterone in ovarian cancer tissue, since post-menopausal women with ovarian cancer presented lower median tissue hormone levels, most pronounced between malignant and benign tumors; median (25 and 75 percentile) estradiol; 9.40 (6.67-15.50) vs 16.44 (12.49-23.20), p=0.02 and progesterone; 308 (240-575) vs 957 (553-1143) pmol/g wet weight, p<0.01, n=81. Lower concentrations of estradiol, but not progesterone, were found in ovarian cancer tissue, ovarian cyst fluid and peripheral serum in patients with FIGO stages 3 and 4 than in stages 1 and 2. The novel finding of a large ovarian tissue to serum difference of both estradiol and progesterone indicates an important role of ovarian tissue concentrations in tumor biology and raises the question of adequate doses of anti-hormonal therapy in women with ovarian cancer.

Relation between mood, social support and the quality of life in patients with laryngectomies.

Two hundred laryngectomized members of the Norwegian Society of Laryngectomies (NSL), a subsidiary of the Norwegian Cancer Society, were invited to answer the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 QOL questionnaires to assess their quality of life (QOL). The Beck Depression Inventory (BDI) scores, their levels of social support and their marital and educational statuses were also determined. In addition, the activity levels of each patient within the NSL were assessed. The questionnaires were returned anonymously by 104 patients. The results of this sample were compared with the responses to the EORTC QLQ C30/H&N35 by all of the survivors of treatment for head and neck squamous cell carcinoma (HNSCC) in western Norway between 1992 and 1997. This sample included 96 of 106 eligible patients. The QLQ-C30 symptom scores include, e.g., dyspnea, smell and taste. However, neither the QLQ-C30 functional scores nor the disease-specific scores of the people with laryngectomies differed from the general HNSCC-treated population. The level of social support by family, friends and neighbors was not associated with the QOL, whereas high BDI scores were associated with reduced QOL by most measured indexes. Furthermore, a positive association was determined between the level of activity within the NSL and QOL. This relation was to some extent secondary to differential BDI scores. In conclusion, the QOL of people with laryngectomies is relatively similar to a general population of patients treated because of HNSCC, is related to the activity level within a patient interest organization and is associated with a lower mood level.

The Fas/FasL system and T cell apoptosis in HIV-1-infected lymphoid tissue during highly active antiretroviral therapy.

Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. In the present study we have phenotyped apoptotic T cells in tonsillar lymphoid tissue from 11 HIV-1-infected patients by flow cytometry light-scatter characteristics during 48 weeks of highly active antiretroviral therapy (HAART). We found that the decline in tonsillar viral load was associated with a decrease in the proportion of apoptotic CD4+ and CD8+ T cells. CD4 cell apoptosis was predominantly seen within the memory CD28+ Fas+ FasL+ population. The increased level of apoptotic CD8+ T cells was found among activated Fas+ memory cells irrespective of CD28 and FasL expression. These T cell subsets were expanded in untreated infection, but normalized with therapy. We conclude that HIV-1 triggers FasL-mediated apoptosis of uninfected CD4+ T cells, whereas CD8+ T cell apoptosis is driven by chronic immune activation. Virus suppression reverses both of these mechanisms, contributing to immune reconstitution during HAART.

Clinical and pregnancy outcome following ectopic pregnancy; a prospective study comparing expectancy, surgery and systemic methotrexate treatment.

BACKGROUND: The improved possibility of an early diagnosis of ectopic pregnancy by use of serial quantitative beta-subunit human chorionic gonadotropin hormone levels together with transvaginal ultrasound has opened up options for conservative treatment. Systemic methotrexate treatment of unruptured ectopic pregnancy has emerged as a safe and effective alternative to surgical procedures. The aim of the present study was to investigate the effectiveness of methotrexate treatment in routine clinical practice, but also to assess pregnancy outcome during a 2.5-year follow-up period. METHODS: All patients presenting to the Department of Obstetrics and Gynecology, Umeå University Hospital, with signs and symptoms of ectopic pregnancy between January 1, 1995 and December 31, 1997 were included in this prospective study. Patients with ectopic pregnancy were either managed expectantly, treated with methotrexate or by laparoscopic or open surgery (salpingostomy/salpingectomy). Systemic methotrexate (Pharmacia & Upjohn, Stockholm, Sweden) was administered as an intramuscular injection of 50 mg/m(2). RESULTS: One hundred and seven patients presented with signs and symptoms of a possible ectopic pregnancy, of these 89 patients eventually were diagnosed as having an ectopic pregnancy. Twenty-six (29%) patients were treated with methotrexate, 46 (52%) patients with laparoscopy or laparotomy, and 17 (19%) patients by expectant management. Success rate in the methotrexate group, after one or more injections, was 77% (20 patients out of 26). The mean time to resolution was 24+/-9 days. There was no difference in pregnancy rate following methotrexate treatment compared to surgical treatment. CONCLUSIONS: Systemic single-dose methotrexate treatment is a safe treatment option with a reasonably high success rate, with similar probability of a later intrauterine pregnancy as conventional surgical treatment.

Monocyte and monocyte-derived macrophage secretion of MCP-1 in co-culture with autologous malignant and benign control fragment spheroids.

This study was performed in order to determine how monocytes and macrophages in co-culture with autologous head and neck squamous cell carcinoma (HNSCC) tumor tissue regulate the secretion of monocyte chemotactic protein-1 (MCP-1). The levels of MCP-1 were measured when autologous monocytes or monocyte-derived macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)-spheroids established from HNSCC tumors or benign mucosa serving as control. MCP-1 secretion from co-culture stimulated monocytes and MDMs was increased compared to spontaneous MCP-1 secretion. With prolonged co-culture, MDMs showed a steady-state MCP-1 secretion above background levels for up to 96 h, even with change of co-culture media every 24 h. Addition of an anti-MCP-1 antibody to the medium decreased co-culture-induced monocyte IL-6 secretion. Addition of lipopolysaccharide (LPS) (1 [microg/ml) reduced MCP-1 secretion compared to spontaneous secretion in monocyte cultures. F-spheroids also secrete MCP-1, but at insignificant levels compared to the MCP-1 secretion from monocytes and MDMs. MCP-1 secretion from monocytes/MDMs is regulated differently when co-culture stimulation is compared to LPS-stimulation. Monocytes and MDMs expressed MCP-1 mRNA at a high level in all tested conditions: stimulated in co-culture, not stimulated or stimulated with LPS, indicating post-transcriptional regulation of MCP-1 secretion. The secretion of MCP-1 from tumor-derived F-spheroids, and the maintenance of co-culture MCP-1 secretion from MDMs in vitro, suggests that tumor-associated macrophages are a source of MCP-1 in HNSCC tumors.

High prevalence of influenza specific antibody secreting cells in nasal mucosa.

Secretory immunoglobulin A (SIgA) provides the first line of defence against pathogens initiating infection via the mucosal route, e.g. the influenza virus. The aim of this study was to examine the basal level of influenza-specific antibody-secreting cell (ASC) in the local mucosa of the upper respiratory tract. Nineteen patients scheduled for tonsillectomy were enrolled for the study, and they had not experienced influenza during the previous year. Tonsils, blood, oral fluid and a nasal biopsy were sampled, and the basal levels of ASC and antibodies (Abs) were determined. We found low numbers of influenza-specific ASC in the blood and tonsils, but there were about 10-100 times higher numbers of specific ASC in the nasal mucosa tissue despite no recent influenza exposure. Thus, the basal level of influenza-specific ASC in the mucosa of the respiratory tract may be important in the protection against influenza infection.

Human autologous monocytes and monocyte-derived macrophages in co-culture with carcinoma F-spheroids secrete IL-6 by a non-CD14-dependent pathway.

The secretion of interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha were compared when freshly isolated autologous monocytes or monocytederived macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)-spheroids established from a series of head and neck squamous cell carcinoma (HNSCC) patients. F-spheroids were generated from the malignant tumour (M-spheroids) or from benign mucosa (B-spheroids) from which the tumour originated control. If monocytes maturated towards MDMs before co-culture, the IL-6 secretion declined dependent on the extent of the MDM maturation by both M- and B-spheroid stimulation. When MDMs maturated in continuous co-culture, a steady-state secretion of IL-6 continued for several days but diminished when the culture medium was changed every 24 h. No co-culture-induced IL-1 beta or TNF-alpha was determined. Both the cytokine secretion and the mRNA gene expression revealed a different monocyte/MDM activation when co-culture and lipopolysaccharide (LPS)-stimulation were compared. Addition of anti-CD14 (10 microg/ml) decreased monocyte LPS-stimulated, but increased monocyte co-culture stimulated IL-6 secretion. In conclusion, M- and B-spheroids similarly stimulated monocytes and to a lesser extent MDMs. MDMs that maturated with F-spheroids present, retained responsiveness at the monocyte level. Co-culture-induced monocyte stimulation, as measured by IL-6 secretion, was not dependent on activation via the CD14 molecule.