Development of advanced photon calibrator for Kamioka gravitational wave detector (KAGRA).

The Kamioka Gravitational wave detector (KAGRA) cryogenic gravitational-wave observatory has commenced joint observations with the worldwide gravitational wave detector network. Precise calibration of the detector response is essential for accurately estimating parameters of gravitational wave sources. A photon calibrator is a crucial calibration tool used in laser interferometer gravitational-wave observatory, Virgo, and KAGRA, and it was utilized in joint observation 3 with GEO600 in Germany in April 2020. In this paper, KAGRA implemented three key enhancements: a high-power laser, a power stabilization system, and remote beam position control. KAGRA employs a 20 W laser divided into two beams that are injected onto the mirror surface. By utilizing a high-power laser, the response of the detector at kHz frequencies can be calibrated. To independently control the power of each laser beam, an optical follower servo was installed for power stabilization. The optical path of the photon calibrator's beam positions was controlled using pico-motors, allowing for the characterization of the detector's rotation response. Additionally, a telephoto camera and quadrant photodetectors were installed to monitor beam positions, and beam position control was implemented to optimize the mirror response. In this paper, we discuss the statistical errors associated with the measurement of relative power noise. We also address systematic errors related to the power calibration model of the photon calibrator and the simulation of elastic deformation effects using finite element analysis. Ultimately, we have successfully reduced the total systematic error from the photon calibrator to 2.0%.

Indirect impact of the COVID-19 pandemic on the incidence of non-COVID-19 infectious diseases: a region-wide, patient-based database study in Japan.

OBJECTIVES: The COVID-19 pandemic has forced people to change many behaviours, including physical distancing, hygiene measures and lifestyles. This study aimed to evaluate the indirect impact of the COVID-19 pandemic on the incidence of non-COVID-19 infections and medical care costs/visits using health insurance claims. STUDY DESIGN: This was an observational study using patient-based administrative claims covering approximately 800,000 insured persons and their dependents in the Mie Prefecture in Japan. METHODS: This study identified non-COVID-19 infectious disease incidences, number of outpatient visits and healthcare costs between 2017 and 2021. Each year was divided into quarters. The adjusted incidence rate ratios (IRRs) during the pandemic (January 2020 to September 2021) and during the prepandemic period (January 2017 to December 2019) were determined using Poisson regression. RESULTS: The adjusted influenza IRRs from April 2020 were close to zero. The incidence of upper respiratory tract infections and bacterial pneumonia was significantly reduced (IRRs range: 0.39-0.73 and 0.43-0.84, respectively). Gastrointestinal and urinary tract infection incidences decreased by approximately 30% and 10%, respectively. In contrast, sexually transmitted infections (STIs), including syphilis, gonococcal infection and Chlamydia trachomatis infection, did not decrease during the pandemic but increased significantly between April and June 2021 (adjusted IRR, 1.37; 95% confidence interval, 1.18-1.60). The adjusted IRRs for outpatient visits and healthcare costs were 0.86-0.93 and 0.91-0.97, respectively. CONCLUSIONS: In contrast to other infections, STIs did not decrease during the COVID-19 pandemic. The IRR of STIs during the pandemic period is an area of public health concern. Appropriate screening and medical consultations are strongly recommended.

Swelling of Doubly Magic

Interaction cross sections for ^{42-51}Ca on a carbon target at 280 MeV/nucleon have been measured for the first time. The neutron number dependence of derived root-mean-square matter radii shows a significant increase beyond the neutron magic number N=28. Furthermore, this enhancement of matter radii is much larger than that of the previously measured charge radii, indicating a novel growth in neutron skin thickness. A simple examination based on the Fermi-type distribution, and mean field calculations point out that this anomalous enhancement of the nuclear size beyond N=28 results from an enlargement of the core by a sudden increase in the surface diffuseness of the neutron density distribution, which implies the swelling of the bare ^{48}Ca core in Ca isotopes beyond N=28.

Ring and unimodal angular-frequency distribution of THz emission from two-color femtosecond plasma spark.

We study angular and frequency-angular distributions of the terahertz (THz) emission of the low-frequency region (0.3-3 THz) from a two-color femtosecond plasma spark experimentally and in three-dimensional numerical simulations. We investigate the dependence of the angular shapes of the THz radiation on focusing conditions and pulse durations by using two laser facilities (pulse durations 35 and 150 fs) for different focusing geometries. Our experiments and simulations show that decrease in the numerical aperture from NA ≈0.2 to NA ≈0.02 results simultaneously in (I) squeezing of the THz angular distribution and (II) formation of the bright conical emission in the THz range. The moderate focusing NA ≈0.05, which forms the relatively narrow unimodal THz angular distribution, is identified as optimal in terms of angular divergence. Numerical simulations with carrier wave resolved show that bright THz ring structures appear at the frequencies ≥2 THz for longer focuses (NA ≈0.02), while for optimal focusing conditions NA ≈0.05 the conical emission develops at THz frequencies higher than 10 THz.

Influence of losartan intake on the circadian rhythm of melatonin secretion in humans.

It has been reported that losartan, an angiotensin II receptor blocker, alters the circadian rhythm of melatonin secretion and significantly reduces melatonin production. However, this finding has been confirmed at the animal experiment level only, and there are no reports of studies in humans. Therefore, we performed this study to confirm the reproducibility of the aforementioned findings of animal experiments in humans. Ten male subjects who were in good general health and free from any medical condition were recruited for this study. After a preliminary observation period of 7 days, the subjects received oral losartan treatment, 50 mg daily for 7 days. Blood samplings for measurement of the plasma melatonin concentrations were performed on day 7 of the preliminary observation period and day 7 of the losartan treatment period. The circadian rhythm of melatonin secretion after the 7-day treatment with losartan showed no significant difference from that recorded before the losartan administration. The significant decrease of the home blood pressure was observed on the afternoons. The blood samples showed significant decrease of the serum sodium and uric acid levels, along with a significant increase of the serum potassium level. The pharmacological actions of losartan at the ordinarily used clinical dose level were confirmed in humans, however, no significant inhibitory effect of the drug on melatonin secretion could be confirmed. These results are expected to be useful for guiding the proper use of angiotensin II receptor blockers.

Prolactin induces the production of Th17 and Th1 cytokines/chemokines in murine Imiquimod-induced psoriasiform skin.

BACKGROUND: Prolactin (PRL) is a pituitary-derived neuropeptide hormone that has been suggested to promote the development of psoriasis, a Th17/Th1-mediated inflammatory dermatosis. PRL increases the expression of Th1 cytokines; however, its effects on Th17 responses are unknown. OBJECTIVE: This study aims to determine the in vivo effects of PRL on the expression of Th17 cytokines/chemokines in imiquimod-induced psoriasiform skin inflammation in mice. METHODS: BALB/c mice were intraperitoneally injected with PRL or phosphate-buffered saline, and imiquimod cream or Vaseline was applied to the shaved back skin for six consecutive days. RESULTS: Intraperitoneal PRL increased the mRNA levels of IL-17A, IL-17F, IL-22, IL-23p19, IL-12p40, CCL20 and STAT3 in imiquimod-treated skin. Mice treated with imiquimod plus PRL, but not those treated with imiquimod plus phosphate-buffered saline, showed significantly increased mRNA levels of TNF-α, IFN-γ, IL-12p35 and CXCL2 compared with controls. Intraperitoneal PRL increased the numbers of CD3(+) and GR-1(+) cells in the dermis of imiquimod-treated skin. CONCLUSIONS: These results suggest that intraperitoneal PRL enhances the expression of Th17 and Th1 cytokines/chemokines, and augments inflammation in imiquimod-induced psoriasiform skin. Prolactin may thus exacerbate psoriasis through the enhancement of Th17/Th1 responses.

Ciclosporin A inhibits production of interleukin-12/23p40 and interleukin-23 by the human monocyte cell line, THP-1.

Ciclosporin (Cs)A is an effective treatment for psoriasis. However, to date, the effect of CsA on the production of interleukins (ILs) is unknown. We investigated how CsA affects production of IL-12/23p40 and IL-23 production by the human monocyte cell line, THP-1, which is able to differentiate into macrophage-like cells or normal human keratinocytes (NHKs). THP-1 cells were preincubated with CsA, then stimulated with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid or adenosine triphosphate. The levels of IL-12/23p40 and IL-23 released into the supernatant were assayed by ELISA. CsA significantly reduced both IL-12/23p40 and IL-23 production by LPS-stimulated THP-1 cells, but not in LPS-stimulated macrophage-like differentiated THP-1 cells. None of the stimuli used significantly induced either IL-12/23p40 or IL-23 production in NHKs. CsA inhibits not only IL-12/23p40 and IL-12p70, but also heterodimeric IL-23 production by human monocytes, which may be one possible mechanism for the therapeutic efficacy of CsA in psoriasis.

Effect of enterotoxigenic Escherichia coli vaccine on innate immune function of bovine mammary gland infused with lipopolysaccharide.

The effects of using an enterotoxigenic Escherichia coli vaccine on innate immune responses following intramammary infusion of lipopolysaccharide (LPS) were investigated in midlactation Holstein-Friesian cows. Seven out of 14 cows were inoculated with E. coli vaccine. Three weeks later, 100 µg of LPS dissolved in 10 mL of saline was infused into 1 quarter of all cows. Milk was collected every hour from infusion to 12 h after infusion, and twice daily (at 0900 and 1600 h) for 4 d. Blood samples were collected 0, 4, 8, 24, 48, 72, and 96 h after infusion. Rectal temperatures and milk yields were measured. The somatic cell count (SCC), lingual antimicrobial peptide concentration, lactoperoxidase (LPO) activity, and lactoferrin (LF) concentration in milk, and haptoglobin concentration in serum were determined. The mean rectal temperature in vaccinated cows was higher than in control cows at 10 h. The mean milk yield was decreased significantly in the infused quarter of control cows at 24 h compared with pretreatment, but not in vaccinated cows. The mean SCC in milk from vaccinated cows at 12 and 55 h was significantly lower than that of control cows. The lingual antimicrobial peptide and LF concentrations were significantly lower at 8 h and 55 h, respectively, in vaccinated cows than in control cows. The mean antibody titer in the serum against the vaccine at the time of LPS infusion into vaccinated cows was significantly higher than in control cows. These antibody titers were positively correlated with the peak concentrations of LPO and LF in milk following challenge; therefore, cows with a high antibody titer were accompanied by high LPO activity and LF concentration in milk. These results suggest that vaccination suppresses the innate immune reaction after intramammary LPS infusion; however, the elevated antibody titer was unlikely to be responsible for the modification of the innate immune reaction.

Decreased serum LL-37 and vitamin D3 levels in atopic dermatitis: relationship between IL-31 and oncostatin M.

BACKGROUND: Skin lesions with atopic dermatitis (AD) are associated with dysregulated expression of LL-37 and enhanced expression of IL-22, thymic stromal lymphopoietin (TSLP), IL-25, IL-31, and oncostatin M. Vitamin D3 enhances LL-37 production in keratinocytes. This study aimed to examine the serum levels of LL-37 and vitamin D3 and their regulation of cytokine production in patients with AD. METHODS: Serum levels of LL-37 and 25-hydroxyvitamin D3 were analyzed by ELISA. The effects of 1,25-dihydroxyvitamin D3 or LL-37 on cytokine production in T cells or keratinocytes were analyzed by ELISA and real-time PCR. RESULTS: Serum levels of LL-37 and 25-hydroxyvitamin D3 were decreased in patients with AD compared to normal donors and were correlated in both groups. Serum levels of LL-37 correlated with those of oncostatin M and IL-31 in normal donors and patients with AD, while 25-hydroxyvitamin D3 levels did so only in normal donors. 1,25-dihydroxyvitamin D3 increased LL-37 production in human keratinocytes and neutrophils. 1,25-dihydroxyvitamin D3 and LL-37 enhanced the oncostatin M and IL-31 production in CD3/28-stimulated T cells, but did not alter IL-25 and TSLP production in TNF-α-stimulated keratinocytes. In CD3/28-stimulated T cells, 1,25-dihydroxyvitamin D3 reduced the IL-22 production, while LL-37 enhanced it. These effects of 1,25-dihydroxyvitamin D3 and LL-37 were suppressed by vitamin D receptor antagonist and pertussis toxin, respectively. CONCLUSIONS: Systemic vitamin D3 levels are reduced in patients with AD, which may contribute to decreased systemic LL-37 levels. LL-37 may systemically potentiate the oncostatin M and IL-31 production in normal donors and patients with AD, while vitamin D3 may do so only in normal donors.

Serum lipocalin-2 levels are increased in patients with psoriasis.

The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis.

The effect of an octacalcium phosphate co-precipitated gelatin composite on the repair of critical-sized rat calvarial defects.

This study was designed to investigate the extent to which an octacalcium phosphate/gelatin (OCP/Gel) composite can repair rat calvarial critical-sized defects (CSD). OCP crystals were grown with various concentrations of gelatin molecules and the OCP/Gel composites were characterized by chemical analysis, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), selected area electron diffraction (SAED) and mercury intrusion porosimetry. The OCP/Gel composite disks received vacuum dehydrothermal treatment, were implanted in Wistar rat calvarial CSD for 4, 8 and 16 weeks, and then subjected to radiologic, histologic, histomorphometric and histochemical assessment. The attachment of mouse bone marrow stromal ST-2 cells on the disks of the OCP/Gel composites was also examined after 1 day of incubation. OCP/Gel composites containing 24 wt.%, 31 wt.% and 40 wt.% of OCP and with approximate pore sizes of 10-500 µm were obtained. Plate-like crystals were observed closely associated with the Gel matrices. TEM, XRD, FTIR and SAED confirmed that the plate-like crystals were identical to those of the OCP phase, but contained a small amount of sphere-like amorphous material adjacent to the OCP crystals. The OCP (40 wt.%)/Gel composite repaired 71% of the CSD in conjunction with material degradation by osteoclastic cells, which reduced the percentage of the remaining implant to less than 3% within 16 weeks. Of the seeded ST-2 cells, 60-70% were able to migrate and attach to the OCP/Gel composites after 1 day of incubation, regardless of the OCP content. These results indicate that an OCP/Gel composite can repair rat calvarial CSD very efficiently and has favorable biodegradation characteristics. Therefore, it is hypothesized that host osteoblastic cells can easily migrate into an OCP/Gel composite.

Control of magnetic dipole terahertz radiation by cavity-based phase modulation.

Although it is well accepted that the ultrafast manipulation of spins or magnetization in solid promises potential applications in coherent terahertz (THz) radiation source, spintronics and quantum information processing, their performance is significantly limited by the weak coupling between radiation field and magnetic dipole oscillation. For such 'weak' magnetic system, we propose an effective and simple route based on the cavity-based phase modulation technique towards the efficient energy extraction, demonstrated via controlling the magnetic dipole THz radiation generated in the nonlinear Raman process from antiferromagnetic (AFM) NiO. An asymmetric coupled Fabry-Pérot (FP) cavity is constituted by simply placing a metallic planar mirror in the vicinity of a NiO slab. The energy-extraction (THz radiation) can be effectively manipulated by changing the NiO-mirror distance to modulate the phase relation between the magnetic wave and the induced magnetization in NiO. The distinct radiation control can be observed and the experiments are well explained by numerically analyzing the radiation dynamics that highlights the role of phase modulation during the radiation process.

Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes.

Psoriasis patients are frequently associated with metabolic syndromes. Such associations are possibly mediated by adipokines. We investigated the in vitro effects of visfatin (an adipokine) on chemokine expression in human keratinocytes. Normal human keratinocytes were incubated with visfatin, and their chemokine production was analyzed by ELISA and RT-PCR. Visfatin enhanced TNF-α-induced CXC chemokine ligand (CXCL) 8, CXCL10, and CC chemokine ligand (CCL) 20 secretion and mRNA expression in keratinocytes, although visfatin alone was ineffective. A small interfering RNA against nuclear factor-κB (NF-κB) p65 suppressed the visfatin-induced production of CXCL8, CXCL10, and CCL20 whereas a small interfering RNA against signal transducer and activator of transcription (STAT) 3 suppressed CXCL8 induction. This indicates the involvement of NF-κB in CXCL8, CXCL10, and CCL20 induction by visfatin and the involvement of STAT3 in CXCL8 induction. Visfatin alone increased the transcriptional activity and tyrosine phosphorylation of STAT3, which was suppressed by Janus kinase (JAK) 2 inhibitor. Visfatin enhanced basal and TNF-α-induced NF-κB activity and inhibitory κB (IκB) α phosphorylation, which was suppressed by IκB kinase inhibitor. Visfatin induced the tyrosine and serine phosphorylation of JAK2 and IκB kinase α/ß, respectively. Intraperitoneal injection of visfatin elevated mRNA and protein levels of CXCL1, CXCL10, and CCL20 in murine skin. These results suggest that visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes and homologous chemokine production in murine skin. Visfatin may induce the infiltration of type 1 or type 17 helper T cells or neutrophils to the skin via chemokine induction and thus link metabolic syndromes to psoriasis.

Discovery of a patient with strongly suspected bullous pemphigoid in a ward by oral health care providers.

OBJECTIVES: Oral health care providers may discover systemic diseases incidentally from signs observed in the oral cavity. Here, we report a case in which oral health care providers in a hospital discovered a patient with strongly suspected bullous pemphigoid (BP), which is a relatively rare but important disease, in a ward. METHODS: The patient was a 78-year-old Japanese woman admitted to our hospital because of severe Alzheimer's disease. We discovered recurrent ulcers in the oral mucosa and skin when performing oral care in her ward. Biopsy could not be performed safely because of involuntary biting. We performed blood tests for anti-BP180-NC16a antibody, which is autoantibody specific for BP. RESULTS: The patient had a very high anti-BP180-NC16a antibody titre. We consulted a dermatologist regarding her clinical course and the clinical features of the oral mucosa and skin along with blood test results. BP was very strongly suspected. DISCUSSION: In cases in which oral health care providers suspect their patients may have BP, appropriate examination and provision of information to the doctor are important. Oral health care providers should have knowledge about systemic diseases, the signs of which appear in oral cavity to avoid missing important systemic diseases.

Leukotriene B(4) enhances tumour necrosis factor-alpha-induced CCL27 production in human keratinocytes.

BACKGROUND: A chemokine CCL27 recruits skin-homing T cells. CCL27 production by epidermal keratinocytes is dependent on nuclear factor-kappaB (NF-kappaB) activity and is enhanced in lesions with atopic dermatitis or allergic contact dermatitis. A lipid mediator leukotriene B(4) (LTB(4)) may be involved in the development of these allergic dermatoses. LTB(4) acts on cell surface G-protein-coupled receptors, BLT1 and BLT2. OBJECTIVE: The aim of this study was to investigate the in vitro effects of LTB(4) on CCL27 production in human keratinocytes. METHODS: Keratinocytes were incubated with TNF-alpha and LTB(4). CCL27 secretion and mRNA levels were analysed by ELISA and RT-PCR, respectively. NF-kappaB activities were analysed by luciferase assays. Protein levels or phosphorylation status were analysed by cell-based ELISA. RESULTS: LTB(4) alone did not enhance CCL27 production and modestly enhanced NF-kappaB activity in human keratinocytes. However, LTB(4) potently enhanced TNF-alpha-induced CCL27 secretion and mRNA expression and NF-kappaB activity. LTB(4) alone or together with TNF-alpha, induced phosphorylation and degradation of inhibitory NF-kappaB alpha (IkappaBalpha) and phosphorylation of NF-kappaB p65. These effects of LTB(4) were suppressed by BLT1 antagonist U75302, pertussis toxin, phosphoinositide-3 kinase (PI3K) inhibitor LY294002 and extracellular signal-regulated kinase (ERK) kinase inhibitor U0126, but not by BLT2 antagonist LY255283. LTB(4) induced phosphorylation of ERK and Akt, downstream kinase of PI3K; LY294002 suppressed phosphorylation of both kinases while U0126 suppressed only the former. CONCLUSION: These results suggest that LTB(4) may enhance TNF-alpha-induced CCL27 production by activating NF-kappaB via the BLT1/G(i/o)/PI3K/ERK pathway in human keratinocytes. LTB(4) may contribute to the enhanced CCL27 production of keratinocytes in lesions with atopic dermatitis or allergic contact dermatitis.

Terahertz wave polarization rotation with double layered metal grating of complimentary chiral patterns.

We propose and demonstrate polarization rotation of a terahertz (THz) electromagnetic wave by using two-dimensional gratings consisting of two displaced layers of gold film with complimentary chiral patterns with four-fold symmetry. We develop a time domain THz polarimetry method with three wire grid polarizers and distinguish optical activity from optical anisotropy. We obtain the isotropic polarization rotation of a terahertz wave free from the birefringence of the structures. Results indicate the possibility of controlling THz polarization with artificial chiral structures fabricated with thin metal films.

Hypoxia induced by benign intestinal epithelial cells is associated with cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway.

Cyclooxygenase-2 (COX-2) plays important roles in tumor development. Especially in the early-stage colorectal tumors, COX-2 expression is often observed in the tumor stroma. However, the mechanism regulating such stromal expression of COX-2 remains unknown. In the present study, we simulated the indirect interaction between epithelial cells and stromal cells in the process of colorectal tumor development using an in vitro co-culture model in which NIH3T3 fibroblasts were co-cultured with 'sparsely' or 'densely' populated intestinal epithelial cells, Intestine-407 as a model of premalignant or benign intestinal epithelial cells, and DLD-1 and Caco-2 as models of malignant epithelial cells. COX-2 expression in NIH3T3 fibroblasts was upregulated when co-cultured with the 'dense' epithelial cells regardless of their character. Interestingly, there was pericellular hypoxia in the vicinity of NIH3T3 fibroblasts when co-cultured with 'dense' epithelial cells, and the recovery of the partial pressure of oxygen level resulted in the reduction of enhanced COX-2 expression only in NIH3T3 fibroblasts co-cultured with 'dense' Intestine-407 cells. Furthermore, COX-2 expression was also reduced by the inhibition of transcription factor AP-1. Thus, pericellular hypoxia of the stromal cells caused by densely populated epithelial cells may be one of the potent COX-2 enhancers before completion of malignant transformation during intestinal tumor development.

Genetic characteristics of western North Pacific sei whales, Balaenoptera borealis, as revealed by microsatellites.

Genetic characteristics of sei whales, Balaenoptera borealis, inhabiting the western North Pacific were analyzed at 17 microsatellite loci in a total of 89 whales obtained from the area between 37 degrees N-45 degrees N and 147 degrees E-166 degrees E in 2002 (N=39) and 2003 (N=50). All the loci analyzed were polymorphic over the samples, some of the loci had more than 10 alleles, indicating a high level of genetic variation within samples. No significant deviation from the expected Hardy-Weinberg genotypic proportion was observed at the 17 loci in the samples. No evidence of genetic heterogeneity in allele frequencies was observed between sexes within samples as well as between the two temporally different samples, indicating a single population of sei whales inhabiting the western North Pacific. We finally tested and demonstrated that the population appeared not to suffer from genetic bottleneck as a result of population decline from past commercial whaling.

Possible role of REG Ialpha protein in ulcerative colitis and colitic cancer.

BACKGROUND AND AIMS: Although regenerating gene (REG) Ialpha protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Ialpha gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Ialpha gene expression and whether REG Ialpha protein has a trophic and/or an antiapoptotic effect on colon cancer cells. METHODS: Expression of REG Ialpha mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Ialpha promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Ialpha protein on growth and H(2)O(2) induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. RESULTS: REG Ialpha protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ialpha mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ialpha promoter activity was enhanced by stimulation with interferon gamma or interleukin 6. REG Ialpha protein promoted cell growth and conferred resistance to H(2)O(2) induced apoptosis in LoVo cells. REG Ialpha protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. CONCLUSIONS: The REG Ialpha gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.