Effects of particulate matter on healthy human skin: a panel study using a smartphone application measuring daily skin condition.

BACKGROUND: The influence of particulate matter (PM) on human health has recently attracted attention. However, most previous studies have been limited to diseased skin. OBJECTIVES: To evaluate the effects of PM on healthy skin. METHODS: The study enrolled 188 healthy volunteers without any skin disease during winter and early spring. Every day for 14 days, they recorded their skin states using a smartphone application, which automatically scored facial skin condition in terms of wrinkle, brown-spot and trouble indexes based on a selfie. Subjects recorded information about their personal lifestyles such as sleeping time and outdoor activity. Air pollution and meteorological information were collected during the same period as well. We analysed the correlation between daily skin condition and environmental factors. RESULTS: Overall, 2625 person-days were obtained for 3 months from February to April. Among the various factors analysed in this study, temperature and PM showed statistically significant relationships with the daily condition. Multivariable analysis showed a cumulative effect, as PM2.5 from 8 to 3 days prior to when daily skin condition was checked had a negative correlation with wrinkle index (P < 0.05). CONCLUSIONS: Inadequate outdoor temperature can immediately impinge on the skin state of even healthy people. PM2.5 may contribute to skin ageing gradually rather than immediately.

Osteoporotic fractures in patients with systemic lupus erythematosus and end stage renal disease.

Background The incidence of end stage renal disease (ESRD) in patients with systemic lupus erythematosus (SLE) is rising. However, the relationship between osteoporotic fractures and SLE in the setting of ESRD remains uninvestigated. The purpose of this study was to compare the frequency of incident osteoporotic fractures in patients with ESRD with and without SLE, to identify risk factors for fractures in patients with SLE and ESRD, and to examine the contribution of these fractures to mortality. Methods Retrospective cohort study of patients with SLE ( n = 716) and a 5% random sample of controls without SLE ( n = 4176) in the United States Renal Data System (USRDS) from years 2006-2008 enrolled in Medicare Part D. Results Fractures occurred in 10.6% ( n = 76) of patients with SLE and ESRD and 12.1% ( n = 507) of patients with ESRD without SLE ( p = 0.24). Older age (adjusted relative risk 1.02, 95% confidence interval 1.01-1.04) was associated with an increased risk for fracture in patients with SLE and ESRD. In multivariable analyses, vertebral and hip fractures more than doubled the risk for mortality. Conclusions The frequency of osteoporotic fractures in patients with SLE and ESRD is similar to the general population of patients with ESRD. Vertebral and hip fractures are significant contributors to mortality in patients with SLE and ESRD. Fracture prevention, in particular, for elderly patients with SLE and ESRD, should be considered. Summary SLE is not an independent risk factor for fractures in patients with ESRD. However, among patients with SLE and ESRD, vertebral and hip fractures are significant contributors to mortality.

The efficacy and tolerability of tarafenacin, a new muscarinic acetylcholine receptor M3 antagonist in patients with overactive bladder; randomised, double-blind, placebo-controlled phase 2 study.

OBJECTIVES: To evaluate the dose-response relationship of tarafenacin, an antimuscarinic agent in development phase, for efficacy and safety, at daily doses of 0.2 and 0.4 mg for the treatment of overactive bladder (OAB) PATIENTS AND METHODS: This multicentre, placebo-controlled, randomised, double-blind, phase 2b study was conducted. Patients were randomised to tarafenacin 0.2 mg, tarafenacin 0.4 mg or placebo daily for 12 weeks. Adult patients with OAB for at least 6 months, with an average of ≥ 8 micturitions per day and ≥ 3 incontinence episodes or a total of ≥ 6 urgency episodes per 3 days were enrolled. The primary objective was to compare the mean changes in the number of micturitions per 24 h of the two doses of tarafenacin compared with placebo from baseline to 12 weeks after treatment. RESULTS: A total of 334 patients were screened, of whom 235 patients were randomised. The mean decrease in the number of micturitions per 24 h from baseline to 12 weeks was statistically higher in the tarafenacin 0.4 mg group (-2.43 ± 2.21 times per day, p = 0.033) and non-statistically significant in the tarafenacin 0.2 mg group (-1.92 ± 2.45 times per day, p = 0.393) when compared with the placebo group (-1.77 ± 2.95 times per day). There were no statistically significant differences in the mean change of urgency episodes per 24 h among three groups. The most common adverse event was dry mouth. There were no significant differences in blurred vision and constipation compared with placebo. CONCLUSIONS: Tarafenacin 0.4 mg decreased the number of micturitions in patients with OAB after 12 weeks compared with placebo, and the dose-response relationship of tarafenacin 0.2 and 0.4 mg was confirmed. Both dose levels of tarafenacin were well tolerated.

Effect of multiple invasive foci on breast cancer outcomes according to the molecular subtypes: a report from the Korean Breast Cancer Society.

BACKGROUND: In this study, the prognostic impact of the presence of the multifocal or multicentric tumor (MMT) and its association with molecular subtypes were investigated. PATIENTS AND METHODS: We investigated the breast cancer metastasis and survival in patients with multifocal or multicentric invasive foci in the same breast. The study population includes 2882 patients in the Seoul National University Hospital Breast Care Center (SNUHBCC) dataset and 41 179 patients in Korean Breast Cancer Registry (KBCR) dataset. RESULTS: From SNUHBCC dataset, we observed a significant role of MMT in developing distant metastasis and death when the tumors were triple-negative subtype. This subtype-specific prognostic importance of MMT in overall survival was also seen in KBCR dataset (HR, 1.32; 95% CI, 1.02-1.69). In tumors <2 cm, the hazard ratios (HRs) for node metastasis and death were similar along the tumor size change in triple-negative subtype, while other subtypes showed a stepwise increment, suggesting the biologic importance of small invasive foci in this subtype. CONCLUSIONS: Our results demonstrate the prognostic importance of MMT in patients with triple-negative breast cancers. Small additional invasive foci in triple-negative breast cancer patients should be considered as clinically relevant tumor deposits.

Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.

BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.

Comparison of cystatin C- and creatinine-based estimation of glomerular filtration rate according to glycaemic status in Type 2 diabetes.

AIMS: The influence of hyperglycaemia on the performance of glomerular filtration rate (GFR) estimating equations remains to be determined. We compared the performance of creatinine-based GFR with cystatin C-based GFR in patients with Type 2 diabetes according to glycaemic status. METHODS: In a cross-sectional study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA(1c) tertiles [HbA(1c) ≤ 75 mmol/mol (9.0%) (n = 70), HbA(1c) 76-95 mmol/mol (9.1-10.8%) (n = 70), HbA(1c) >95 mmol/mol (10.8%) (n = 70)] and measured GFR. Isotopic GFR was measured using renal dynamic imaging with (99m) Tc-diethylene-triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine-based formulae (Cockcroft-Gault-eGFR, the Modification of Diet in Renal Disease equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula-eGFR) and a cystatin C-based formula (cystatin C-eGFR). RESULTS: The isotopic GFR of all patients was 93.1 ± 34.1 ml min(-1) 1.73 m(-2). All methods for estimating GFR underestimated isotopic GFR [Cockcroft-Gault-eGFR (68.8 ± 38.6 ml min(-1) 1.73 m(-2) ) (P < 0.05), Modification of Diet in Renal Disease-eGFR (74.8 ± 31.3 ml min(-1) 1.73 m(-2) ) (P < 0.05), Chronic Kidney Disease Epidemiology Collaboration-eGFR (72.9 ± 26.6 ml min(-1) 1.73 m(-2)) (P < 0.05) and cystatin C-eGFR (83.5 ± 33.2 ml min(-1) 1.73 m(-2)) (P < 0.05)]. In all patient groups, cystatin C-eGFR was less biased and more accurate than the creatinine-based formulae, especially in the group with HbA(1c) > 95 mmol/mol (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR. CONCLUSIONS: Performance of cystatin C-eGFR was superior to creatinine-based GFR in patients with Type 2 diabetes with HbA(1c) >95 mmol/mol (10.8%).

Evaluation of the pharmacokinetics and metabolism of a novel histone deacetylase inhibitor, KBH-A40, in rats.

The pharmacokinetics and metabolism of KBH-A40, a novel δ-lactam-based histone deacetylase inhibitor, were characterized in male Sprague-Dawley rats. KBH-A40 exhibited a high clearance (12.0 ± 2.8 l h⁻¹kg⁻¹), a large volume of distribution at steady state, V(ss) (3.9 ± 1.5 l kg⁻¹), and a short half-life, t1/2 (2.0 ± 0.3 h). KBH-A40 was rapidly converted to its metabolite, KBH-A40 carboxylate, after intravenous (2 and 20 mg kg⁻¹ and oral (10 mg kg⁻¹) administration; the carboxylate metabolite remained at elevated concentrations in the plasma for more than 8 h. Glucuronide conjugate of KBH-A40 was identified qualitatively by using liquid chromatography tandem mass spectrometry in rat plasma. KBH-A40 was rapidly absorbed (t(max) = 0.4 h) after oral dose, consistent with its permeability in Caco-2 cells. Its oral bioavailability was low (14.2-14.8%). An apparent "double peak" phenomenon was observed for both KBH-A40 and KBH-A40 carboxylate after oral administration. KBH-A40 was degraded rapidly by glucuronidation, but not by cytochrome P450-mediated oxidation, in rat liver microsomes. These results suggest that the rapid metabolism of KBH-A40 could be a major reason for its poor pharmacokinetics. Therefore, this work provides valuable structural information to improve pharmacokinetic properties of KBH-A40, a lead compound.

Symptom change after discontinuation of successful antimuscarinic treatment in patients with overactive bladder symptoms: a randomised, multicentre trial.

AIMS: Efficacy of antimuscarinic therapy for overactive bladder (OAB) has been demonstrated; however, the durability of its effects is unknown. The study was conducted to evaluate symptom change and retreatment rate after discontinuation of antimuscarinic therapy. Also, we tried to find risk factors for retreatment. METHODS: This was a prospective, randomised, open-label, multicentre trial at four university hospitals. Women who had OAB symptoms for ≥ 6 months and who showed successful response to 1 month of Tolterodine 4 mg medication were randomly assigned to one of three groups: (A) discontinue medication, (B) 2-month additional medication and (C) 5-month additional medication. After completion of the 1-, 3- or 6-month treatment, patients stopped the medication and were followed up for additional 3 months to assess symptom relapse and retreatment rates. Risk factors for retreatment were evaluated. RESULTS: Of a total of 558 patients who took the study medication, 173 were randomised and 108 (A: 40, B: 40, C: 28) were included in the analysis. At the end of the treatment, the mean micturition frequency was decreased to 8.3/24 h from 11.7/24 h, and the mean urgency episode was decreased to 2.2/24 h from 8.0/24 h. Three months after discontinuation, the micturition frequency and the urgency episode were increased to 9.1/24 and 4.4/24 h respectively. Sixty five per cent of patients requested retreatment, and 62% experienced symptom relapse. Baseline health-related quality of life was the only independent risk factor for retreatment. DISCUSSION AND CONCLUSION: Discontinuation of antimuscarinic therapy resulted in high symptom relapse and retreatment rates regardless of treatment duration. The results provide new information on the durability of the efficacy of antimuscarinics, and may improve treatment efficacy by promoting the medication persistence of antimuscarinics in OAB patients.

Seasonal variation of patulous Eustachian tube diagnoses using climatic and national health insurance data.

OBJECTIVES: This study aimed to analyse if there were any associations between patulous Eustachian tube occurrence and climatic factors and seasonality. METHODS: The correlation between the monthly average number of patients diagnosed with patulous Eustachian tube and climatic factors in Seoul, Korea, from January 2010 to December 2016, was statistically analysed using national data sets. RESULTS: The relative risk for patulous Eustachian tube occurrence according to season was significantly higher in summer and autumn, and lower in winter than in spring (relative risk (95 per cent confidence interval): 1.334 (1.267-1.404), 1.219 (1.157-1.285) and 0.889 (0.840-0.941) for summer, autumn and winter, respectively). Temperature, atmospheric pressure and relative humidity had a moderate positive (r = 0.648), negative (r = -0.601) and positive (r = 0.492) correlation with the number of patulous Eustachian tube cases, respectively. CONCLUSION: The number of patulous Eustachian tube cases was highest in summer and increased in proportion to changes in temperature and humidity, which could be due to physiological changes caused by climatic factors or diet trends.

Genetic polymorphisms of the bovine fatty acid binding protein 4 gene are significantly associated with marbling and carcass weight in Hanwoo (Korean Cattle).

The objective of this study was to investigate an association between polymorphisms in the FABP4 gene and phenotypic variation for marbling and carcass weight (CWT) in a population of Hanwoo steers. We re-sequenced 4.3 kb of the FABP4 gene region in 24 Hanwoo bulls and identified 16 SNPs and 1 microsatellite polymorphism. Of these 16 SNPs, three SNPs [g.2774G>C (intron I), g.3473A>T (intron II) and g.3631G>A (exon III, creating a p.Met >Val amino acid substitution)] were genotyped in 583 steers to assess their association with carcass traits. The g.3473A allele showed a significant increasing effect on CWT (P = 0.01) and the g.3631G allele was associated with higher marbling score (P = 0.006). One haplotype of these three SNPs (CAG) was significantly associated with CWT (P = 0.02) and marbling score (P = 0.05) and could potentially be of value for marker assisted selection in Hanwoo cattle. The CAG haplotype effect for CWT was larger (11.14 +/- 5.03 kg) than the largest single locus effect of g.3473A>T (5.01 +/- 2.2 kg).

Amifampridine to treat Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disabling neuromuscular disease caused by antibodies against presynaptic voltage-gated calcium channels. It reduces the quantal release of acetylcholine (Ach), causing muscle weakness, reduced or absent reflex and dysautonomia. About half of LEMS patients have associated small cell lung cancer. For symptomatic treatment, amifampridine (3,4-diaminopyridine [3,4-DAP]) is ideal because it increases the release of Ach at the presynaptic membrane. Since the first use of 3,4-DAP in LEMS patients in the 1980s, 136 LEMS patients were treated with amifampridines in the open-label studies and 208 patients in the eight randomized studies. These studies showed that amifampridine is the most effective drug for symptomatic treatment in LEMS. Now, 3,4-DAPP (3,4-DAP phosphate) is approved for adult LEMS patients and 3,4-DAP for pediatric patients. The recommended dose is 80 mg a day, divided 3 or 4 times a day. Side effects are usually mild, and the most frequently reported are paresthesia.

Comparison of patulous Eustachian tube patients with and without a concave defect in the anterolateral wall of the tubal valve.

OBJECTIVE: Patulous Eustachian tube appears to be caused by a concave defect in the anterolateral wall of the tubal valve of the Eustachian tube. This study aimed to compare the clinical features of patulous Eustachian tube patients with or without a defect in the anterolateral wall of the tubal valve. METHODS: Sixty-six patients with a patulous Eustachian tube completed a questionnaire, which was evaluated alongside endoscopic findings of the tympanic membrane, nasal cavity and Eustachian tube orifice. RESULTS: Females were more frequently diagnosed with a patulous Eustachian tube, but the valve defect was more common in males (p = 0.007). The ratio of patulous Eustachian tube patients with or without defects in the anterolateral wall of the tubal valve was 1.6:1. Weight loss in the previous six months and being refractory to conservative management were significantly associated with the defect (p = 0.035 and 0.037, respectively). Symptom severity was significantly higher in patients with the defect. CONCLUSION: Patulous Eustachian tube patients without a defect in the anterolateral wall of the tubal valve can be non-surgically treated more often than those with the defect. Identification of the defect could assist in making treatment decisions for patulous Eustachian tube patients.

Transport and metabolism of the antitumour drug candidate 2'-benzoyloxycinnamaldehyde in Caco-2 cells.

The transport and metabolism of the antitumour drug candidate 2'-benzoyloxycinnamaldehyde (BCA) was characterized in Caco-2 cells. BCA disappeared rapidly from the donor side without being transported to the receiver side during its absorptive transport across Caco-2 cells. Its metabolites 2'-hydroxycinnamaldehyde (HCA) and o-coumaric acid (OCA) were formed in both the donor and the receiver sides. HCA, in a separate study, also disappeared rapidly from the donor side, mostly being converted to its oxidative metabolite OCA during its absorptive transport across Caco-2 cells. OCA was transported rapidly in the absorptive direction across Caco-2 cells with a P(app) of 25.4 +/- 1.0 x 10(-6) cm s(-1) (mean +/- standard deviation (SD), n = 3). OCA was fully recovered from both the donor and the receiver side throughout the time-course of this study. Formation of HCA from BCA was inhibited almost completely by bis(p-nitrophenyl)phosphate (BNPP), a selective inhibitor of carboxylesterases (CES), and phenylmethylsulfonyl fluoride (PMSF), a broad specificity inhibitor of esterases in Caco-2 cells, suggesting that this hydrolytic biotransformation was likely mediated predominantly by CES. Conversion of HCA to OCA was inhibited significantly by isovanillin, a selective inhibitor of aldehyde oxidase (AO). Inhibitors for xanthine oxidase (XO) and aldehyde dehydrogenase (ALDH), which are known to be involved in the oxidation of aldehydes to carboxylic acids, did not have a significant effect on the biotransformation of HCA to OCA in Caco-2 cells. In summary, the present work demonstrates that BCA is hydrolysed rapidly to HCA, followed by subsequent oxidation to OCA, in Caco-2 cells. The results provide a mechanistic understanding of the poor absorption and low bioavailability of BCA after oral administration.

Cell cycle and immune-related processes are significantly altered in chronic GVHD.

Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the molecular characteristics underlying chronic GVHD, we analyzed the gene expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering showed that the entire expression profiles of chronic GVHD samples were clearly different from those of the non-GVHD samples, and significance analysis of microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D, were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD patients. Gene ontology annotation revealed that these genes are related to the phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1 and CD3D in separate samples. Pathway-wise global test revealed that differential gene expression in cell cycle and T cell immune-associated pathways were significant between GVHD patients and non-GVHD patients. Seventeen classifier genes selected using a PAM (prediction analysis of microarray) algorithm showed favorable performance (prediction accuracy=0.85) for identifying patients with chronic GVHD. In conclusion, we identified differentially expressed genes and pathways in chronic GVHD patients using microarray analysis, and we also selected diagnostic genes predicting chronic GVHD status.

Multi-organ Metastasis of Fibrolamellar Hepatocellular Carcinoma in a Malayan Gharial (Tomistoma schlegelii).

A 38-year-old Malayan gharial (Tomistoma schlegelii) with a 2-week history of anorexia was found dead and presented for post-mortem examination. Numerous white firm nodules of various sizes were found on the surface of the liver, both left and right kidneys, the spleen and the serosa of the intestinal tract. All masses had similar microscopical appearance and were diagnosed as metastasizing fibrolamellar hepatocellular carcinoma. Immunohistochemically, the tumour cells did not react with antibodies specific for pan-cytokeratin, vimentin or HepPar-1. The anti-HepPar-1 and anti-pan-cytokeratin antibodies also did not react with normal hepatocytes or exocrine pancreatic cells. This is the first description of fibrolamellar hepatocellular carcinoma with metastases in a crocodilian.

Engineering the surface chemistry of lead chalcogenide nanocrystal solids to enhance carrier mobility and lifetime in optoelectronic devices.

We introduce a stepwise, hybrid ligand-exchange method for lead chalcogenide nanocrystal (NC) thin films using the compact-inorganic ligand thiocyanate and the short organic ligand benzenediothiolate. Spectroscopic and device measurements show that hybrid exchange enhances both carrier mobility and lifetime in NC thin films. The increased mobility-lifetime product achieved by this method enables demonstration of optoelectronic devices with enhanced power conversion and quantum efficiency.

API5 confers cancer stem cell-like properties through the FGF2-NANOG axis.

Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5high human cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5+ refractory tumors.

Effects of insertion conditions on tissue strain and vascular damage during neuroprosthetic device insertion.

Long-term integration of neuroprosthetic devices is challenged by reactive responses that compromise the brain-device interface. The contribution of physical insertion parameters to immediate damage is not well described. We have developed an ex vivo preparation to capture real-time images of tissue deformation during device insertion using thick tissue slices from rat brains prepared with fluorescently labeled vasculature. Qualitative and quantitative assessments of damage were made for insertions using devices with different tip shapes inserted at different speeds. Direct damage to the vasculature included severing, rupturing and dragging, and was often observed several hundred micrometers from the insertion site. Slower insertions generally resulted in more vascular damage. Cortical surface features greatly affected insertion success; insertions attempted through pial blood vessels resulted in severe tissue compression. Automated image analysis techniques were developed to quantify tissue deformation and calculate mean effective strain. Quantitative measures demonstrated that, within the range of experimental conditions studied, faster insertion of sharp devices resulted in lower mean effective strain. Variability within each insertion condition indicates that multiple biological factors may influence insertion success. Multiple biological factors may contribute to tissue distortion, thus a wide variability was observed among insertions made under the same conditions.

Applicability of carcinoembryonic antigen-specific monoclonal antibodies to radioimmunoguided surgery for human colorectal carcinoma.

Two carcinoembryonic antigen (CEA)-specific monoclonal antibodies (MAbs), PR1A3 and T84.66, were tested to determine whether they could accurately localize colorectal carcinoma and therefore be applicable in radioimmunoguided surgery (RIGS). Twenty-one tumors by three human colorectal carcinoma cell lines with various levels of CEA expression (KM-12c, C75, and Clone A) were successfully implanted in the intra-abdominal organs of 15 nude mice. The tumors was localized using a portable radioisotope detector (Neoprobe 1000) 48 h after injection of radiolabeled MAbs (10 mCi/mouse) when the precordial counts were <20 per 2 s. Histopathological identification of radiolabeled MAbs were also performed using immunohistochemistry and microautoradiography. Radioactivity counted on a portable radioisotope detector correlated well with that on a gamma counter. The distribution in the blood was significantly greater than in other organs (P < 0.001). Localization indices of the tumor in various organs was from 1.1 to 8.5 in the PR1A3-pretreated mice and 3.0 to 8.6 in the T84.66-pretreated mice. Silver grains and immune staining were distributed in the tumor cells of the PR1A3-pretreated mice, whereas they were in the necrotic debris as well as the tumor cells of the T84.66-pretreated mice. There were significantly more silver grains in the liver in the T84.66-pretreated mice than in the PR1A3-pretreated mice (P = 0.004). The sensitivity and specificity of tumor localization by RIGS were 71.4 and 91.4% in the PR1A3-pretreated mice, whereas they were 60 and 76% in the T84.66-pretreated mice. A study using specific anti-CEA MAbs suggested PR1A3 as an efficient immune probe for RIGS in colorectal carcinoma with a low rate of false-positive detection.