Cytokine responses to fungal pathogens in Kupffer Cells are Toll-like receptor 4 independent and mediated by tyrosine kinases.

Disseminated fungal infections are increasing. However, the interactions between the body's largest population of tissue macrophages, the Kupffer cells and the fungal pathogens are scarcely understood. The aim of this study was to examine the involvement of Toll-like receptor 4 (TLR4) signalling in cytokine production, using primary cultures of rat and murine Kupffer cells exposed to Aspergillus fumigatus and Candida albicans hyphae and conidia. All fungal components induced the release of tumour necrosis factor-alpha (TNF-alpha), but with delayed kinetics compared with lipopolysaccharide (LPS). Candida albicans was the most potent inducer of TNF-alpha protein and mRNA and the only inducer of interleukin-10 (IL-10) in rat Kupffer cells. All fungal components induced enhanced mRNA levels of macrophage inhibitory protein-2 (MIP-2) in the cells, similar to LPS. Inhibitors of Src tyrosine kinases added to cells prior to stimulation led to attenuation in the release of both TNF-alpha (60%, P < 0.05) and IL-10 (70%, P < 0.05) induced by C. albicans conidia but did not influence the LPS-mediated cytokine release. Murine Kupffer cells (C57BL/10J) also released TNF-alpha as well as the chemokines keratinocyte-derived chemokine (KC) and MIP-2 in response to fungal component. Surprisingly, Kupffer cells from TLR4-deficient C57BL/ScCr mice exhibited significantly enhanced production of KC and MIP-2 upon stimulation by fungal components compared with control littermates (P < 0.05). Our study demonstrates that Aspergillus and Candida components induce cytokine production in rat Kupffer cells and that the response to C. albicans conidia involves Src tyrosine kinases. The experiments with TLR4-deficient Kupffer cells suggest that the cytokine response in these cells to fungal component is not mediated by TLR4.

[Urinary problems and prostate-specific antigen in a Norwegian normal population]. / Vannlatingsplager og prostataspesifikt antigen i en norsk normalpopulasjon.

BACKGROUND: Measurements of PSA in serum is crucial in the diagnostic work-up of prostatic diseases. MATERIAL AND METHODS: We have studied the distribution of PSA values in an unselected population of 609 men, and the relation between PSA level and urinary symptoms, age and prostate volume. RESULTS: 87 (14%) men had a PSA concentration at or above the reference value of 4.0 ng/ml. Prostate cancer was verified in 14 (16%) of these men. The probability of having PSA equal to or above 4.0 ng/ml was 12 times greater for men with a prostate volume of 40 cm3 or less than for men with a prostate volume less than 20 cm3. Mean PSA values were higher in men with severe than with mild urinary symptoms, but symptoms were poor predictors of PSA levels. Age was not associated with an increase in PSA level independent of prostate volume. INTERPRETATION: Absence of urinary symptoms does not exclude elevated PSA values and thus not cancer. Most men with PSA equal to or above 10.0 ng/ml will have prostate cancer, but enlarged prostate without cancer can also give elevated PSA values.

Lower urinary tract symptoms, prostate volume and uroflow in norwegian community men.

OBJECTIVE: To describe lower urinary tract symptoms, prostate volume and peak urinary flow rate, and investigate the relationships among urological variables in a community sample of Norwegian men. MATERIALS AND METHODS: A cross-sectional study of 611 men, aged 55-70 years, who underwent a clinical urological examination including uroflowmetry, residual urine measurement, and transrectal ultrasonography of the prostate. All the men completed a questionnaire which included the International Prostate Symptom Score (IPSS). RESULTS: Severe symptoms were reported by 5%, while 23.6% reported moderate symptoms, and the overall median IPSS was 4 (q1 = 25th percentile, 1; q3 = 75th percentile, 9). The median peak flow rate was 15 ml/s (q1 = 11; q2 = 22) while median prostate volume was 30 cm(3) (q1 = 23; q3 = 38), with little variation evident across the narrow age range of 55-70 years. A positive modest correlation (r = 0.176) was found between IPSS and prostate volume, and a negative correlation between IPSS and peak flow rate (r = -0.278). There was a modest correlation between body mass index (BMI) and prostate size, but no significant correlation between BMI and IPSS. CONCLUSION: In this population-based study, moderate lower urinary tract symptoms were reported by 24% and severe symptoms by 5% of community men. The distribution of lower urinary tract symptoms, prostate volume and peak urinary flow rate in Norwegian men is comparable to that described in similar studies conducted in Spain, Holland and USA.

Ischaemic necrosis of lesser curve of stomach after proximal gastric vagotomy.

Of 483 patients treated by proximal gastric vagotomy (PGV) between 1972 and 1986 four (0.8%) developed lesser curve necrosis with perforation and one died of diffuse peritonitis. Gastroscopy 3-6 days after PGV in 26 patients between November 1985 and May 1987 showed that five had developed ischemic ulcers on the lesser curve (19%). One further patient developed lesser curve necrosis with perforation before endoscopy, giving a total of six lesser curve lesions after 26 vagotomies (23%). Endoscopy also showed that most patients had some gastric retention. Ulcers with maximal diameters of 0.4-2 cm were asymptomatic. One patient with a large ischaemic ulcer (3 cm) had an abrupt fall in haemoglobin concentration (from 148 to 73 g/l) as did two patients who developed lesser curve necrosis with perforation and peritonitis (143 to 93, and 159 to 71, respectively). We conclude that ischemic ulcers are relatively common after PGV, that small ulcers are asymptomatic and do not perforate, and that an upper GI bleeding after PGV strongly suggests that lesser curve necrosis has developed.