A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

BIOPHYSICAL PROPERTIES OF SUBTHRESHOLD RESONANCE OSCILLATIONS AND SUBTHRESHOLD MEMBRANE OSCILLATIONS IN NEURONS.

Subthreshold-level activities in neurons play a crucial role in neuronal oscillations. These small-amplitude oscillations have been suggested to be involved in synaptic plasticity and in determining the frequency of network oscillations. Subthreshold membrane oscillations (STOs) and subthreshold resonance oscillations (SROs) are the main constituents of subthreshold-level activities in neurons. In this study, a general theoretical framework for analyzing the mechanisms underlying STOs and SROs in neurons is presented. Results showed that the resting membrane potential and the hyperpolarization-activated potassium channel (h-channel) affect the subthreshold-level activities in stellate cells. The contribution of h-channel on resonance is attributed to its large time constant, which produces the time lag between Ih and the membrane potential. Conversely, the persistent sodium channels (Nap-channels) only play an amplifying role in these neurons.

Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer.

BACKGROUND: Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding. METHODS: Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections. RESULTS: Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26-3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation. CONCLUSIONS: Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia.

Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.

A novel mechanism of glucocorticoid-induced immune suppression: the inhibiton of T cell-mediated terminal maturation of a murine dendritic cell line.

Working with the murine epidermal-derived dendritic cell (DC) line XS52, we have observed previously that antigen-specific interaction with T cells stimulates their "terminal maturation" into fully professional DC. In this study we examined the impact of dexamethasone (DEX) on this T cell-induced event. When added to cocultures of XS52 DC and the KLH-specific Th1 clone HDK-1 in the presence of antigen, DEX at relatively low concentrations (10(-9)-10(-7) M) prevented substantially or completely each of the changes that typify terminal maturation, including (a) secretion of relatively large amounts of IL-1beta, IL-6, and TNFalpha; (b) loss of CD115 (colony-stimulating factor-1 receptor) expression and proliferative responsiveness to colony-stimulating factor-1; and (c) elevated expression of CD86 (B7-2). XS52 cells also underwent terminal maturation upon exposure to lipopolysaccharide alone, and DEX also inhibited effectively each of the same changes, indicating that DC can serve as the direct target of DEX. By contrast, DEX inhibited XS52 DC-stimulated IL-2 secretion by HDK-1 T cells, but not other changes that accompany T cell activation, including the secretion of IFNgamma and TNFalpha and the elevated expression of CD25, CD28, and CD44. These results reveal a new immunosuppressive mechanism of glucocorticoid action, that is, direct inhibition of T cell-mediated terminal maturation by DC.

Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy.

Studies conducted over the last decade demonstrated variable therapeutic efficacy of angiotensin converting enzyme (ACE) inhibitor on the progression of glomerular diseases, including IgA nephropathy. In this study, among patients with biopsy-proven IgA nephropathy, 53 patients in whom creatinine clearance had been monitored over 5 yr were recruited for study. These patients were classified into two groups according to whether or not renal function had declined as determined by the slope of creatinine clearance against time: group 1 had stable renal function; group 2 had declining renal function (average: -6.7 +/- 1.3 ml/min/yr). 21 of 53 patients were treated with ACE inhibitor and followed for 48 wk. Gene polymorphism consisting of insertion (I) or deletion (D) of a 287-bp DNA fragment (presumed to be a silencer element) of the ACE gene was determined by PCR. 46 age-matched individuals without history of proteinuria were analyzed as controls. The DD genotype was significantly more frequent in group 2 (43%) than in controls (7%) or group 1 patients with stable renal function (16%). 48 wk after ACE inhibitor administration, proteinuria significantly decreased in patients with DD genotype but not in those with ID or II genotypes. The results indicate that deletion polymorphism in the ACE gene, particularly the homozygote DD, is a risk factor for progression to chronic renal failure in IgA nephropathy. Moreover, this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progressive deterioration of renal function.

Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese population.

Several lines of evidence suggest that metabolic changes in the kynurenic acid (KYNA) pathway are related to the etiology of schizophrenia. The inhibitor of kynurenine 3-monooxygenase (KMO) is known to increase KYNA levels, and the KMO gene is located in the chromosome region associated with schizophrenia, 1q42-q44. Single-marker and haplotype analyses for 6-tag single nucleotide polymorphisms (SNPs) of KMO were performed (cases = 465, controls = 440). Significant association of rs2275163 with schizophrenia was observed by single-marker comparisons (P = 0.032) and haplotype analysis including this SNP (P = 0.0049). Significant association of rs2275163 and haplotype was not replicated using a second, independent set of samples (cases = 480, controls = 448) (P = 0.706 and P = 0.689, respectively). These results suggest that the KMO is unlikely to be related to the development of schizophrenia in Japanese.

Suppression of dibutylnitrosamine-induced bladder carcinomas in hamsters by dietary indole.

Effect of dietary indole on the urinary bladder tumorigenesis by chronic dibutylnitrosamine (DBN) treatment was evaluated in hamsters. In the first experiment, in which DBN-water and diet were given ad libitum, dietary indole significantly suppressed bladder tumor incidence. The inhibitory effect was more pronounced in males. In the second experiment, in which consumption of both diet and DBN-water was rigidly controlled by pair-feeding, dietary indole again significantly suppressed bladder tumor incidence; its effect was similar in both males and females. This suppressive effect of indole on bladder tumorigenesis contrasted markedly with its failure to suppress tumors at other sites such as nasal sinuses, trachea, esophagus, and fore-stomach.

Comparison between intraperitoneal CO2 insufflation and abdominal wall lift on QT dispersion and rate-corrected QT dispersion during laparoscopic cholecystectomy.

This study compared the effect of intraperitoneal CO2 insufflation with abdominal wall lift on RR interval, QT interval, the rate-corrected QT (QTc) interval, QT dispersion (QTD), and the rate-corrected QTD (QTcD) using computerized measurement during laparoscopic cholecystectomy. Thirty patients scheduled for laparoscopic cholecystectomy were randomly assigned to 2 groups: intraperitoneal CO2 insufflation (CO2 group) or abdominal wall lift (lift group). A 12-lead electrocardiogram was monitored to measure parameters. The RR interval, QT interval, and QTc interval did not change significantly during the study in both groups. The QTD and QTcD in the CO2 group increased significantly during CO2 insufflation, and were significantly higher than those of the lift group. Statistically significant increases of QTD and QTcD, which are associated with an increased risk of arrhythmias and cardiac events, occur during CO2 insufflation, and QTD and QTcD in the CO2 group were significantly higher than those of the lift group.

HpEts, an ets-related transcription factor implicated in primary mesenchyme cell differentiation in the sea urchin embryo.

The mechanism of micromere specification is one of the central issues in sea urchin development. In this study we have identified a sea urchin homologue of ets 1 + 2. HpEts, which is maternally expressed ubiquitously during the cleavage stage and which expression becomes restricted to the skeletogenic primary mesenchyme cells (PMC) after the hatching blastula stage. The overexpression of HpEts by mRNA injection into fertilized eggs alters the cell fate of non-PMC to migratory PMC. HpEts induces the expression of a PMC-specific spicule matrix protein, SM50, but suppresses of aboral ectoderm-specific arylsulfatase and endoderm-specific HpEndo16. The overexpression of dominant negative delta HpEts which lacks the N terminal domain, in contrast, specifically represses SM50 expression and development of the spicule. In the upstream region of the SM50 gene there exists an ets binding site that functions as a positive cis-regulatory element. The results suggest that HpEts plays a key role in the differentiation of PMCs in sea urchin embryogenesis.

Experimental study on pathogenesis and histomorphology of early carcinoma of the extrahepatic bile duct in the Syrian hamster.

To elucidate the pathogenesis of carcinomas in the extrahepatic bile duct, we investigated the histomorphological characteristics of adenomas and early carcinomas induced in the extrahepatic bile duct of hamsters. Syrian hamsters underwent a cholecystoduodenostomy along with a dissection of the common duct, while also being administered N-nitrosobis(2-oxopropyl)amine (BOP). The tumors that arose from the extrahepatic bile duct included 10 adenomas and 55 early carcinomas in 56 of the 156 hamsters sacrificed. All the adenomas were found to be polypoid in shape. The early carcinomas, which were restricted within the mucosal layer of the bile duct, showed the following three different growth patterns: (1) protruding type in 41 (75%), consisting of 27 polypoid and 14 papillary tumors; (2) superficial spreading type in 9 (16%); and (3) periductal glandular type in 5 (9%). There were no depressed tumors observed. Carcinomas existing either alone or associated with adenomas were evident in 12 (22%) tumors, and 11 of these were polypoid. Atypical papillary hyperplasia within the tumor mass was noted in 22 early carcinomas (40%) and was particularly prominent in papillary type tumors. These results support the concept of an adenoma-carcinoma sequence in the majority of polypoid tumors of the extrahepatic bile duct. Atypical papillary hyperplasia might also be premalignant, and these precursor lesions should reflect the growth patterns of tumors, at least in the early stage of tumorigenesis.

Differential expression of sea urchin Otx isoform (hpOtxE and HpOtxL) mRNAs during early development.

Two distinct types of orthodenticle-related proteins (early type: HpOtxE, late type: HpOtxL) of the sea urchin, Hemicentrotus pulcherrimus, have been implicated as enhancer element binding factors of the aboral ectoderm-specific arylsulfatase (HpArs) gene. In order to understand the role of these isoforms during sea urchin development, we have isolated and characterized HpOtx gene. Here we describe the spatial expression patterns of HpOtxE and HpOtxL mRNAs and effects of overexpression of these mRNAs on embryogenesis. Whole-mount in situ hybridization using each isoform-specific probe reveals the complex and dynamic change of expression patterns among three germ layers. HpOtxE mRNA is maternally stored and exists apparently in a nonlocalized manner by the blastula stage. After hatching, HpOtxE transcripts are expressed predominantly in presumptive endoderm cells and gradually decrease during gastrulation. Signals for HpOtxL mRNA are intense at the vegetal half after hatching and subsequently, its expression is restricted to the micromere-derived cells. After primary mesenchyme cell (PMC) ingression, HpOtxL transcripts are localized at the vegetal plate and thereafter, concentrated primarily in ectoderm. Eggs injected with HpOtxE or HpOtxL mRNA develop into similar radialized structures without PMC ingression and gut invagination, whose oral-aboral axes are disrupted. Overexpression of HpOtxE induces accumulation of HpOtxL mRNA at the significantly earlier stages, though HpOtxL overexpression inhibits the accumulation of HpOtxE transcripts. Expression patterns of HpOtxE and HpOtxL in all three germ layers and dramatic morphological changes observed in the mRNA-injected embryos suggest that each HpOtx isoform has an important role in sea urchin embryogenesis.

Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus).

Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting.

Salvage living-donor liver transplantation for liver failure following definitive radiation therapy for recurrent hepatocellular carcinoma: a case report.

A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.

UVB radiation interrupts cytokine-mediated support of an epidermal-derived dendritic cell line (XS52) by a dual mechanism.

We have established long-term dendritic cell lines from the epidermis of newborn mice. These cell lines (XS series) proliferate maximally in response to granulocyte/macrophage-colony stimulating factor, as well as to CSF-1, which is produced by skin-derived NS fibroblast lines and by keratinocytes (albeit in smaller amounts). The purpose of this study was to examine the impact of UVB radiation on CSF-1-mediated interaction of dendritic cells with fibroblasts and keratinocytes. Exposure of NS cells to UVB radiation (unfiltered FS20 sunlamp) decreased CSF-1 production at mRNA and protein levels. Both changes occurred in a dose-dependent fashion, with 50 J/m2 causing a significant reduction. UVB radiation also downregulated CSF-1 mRNA expression by Pam 212 keratinocytes. UVB exposure of XS cells diminished the surface expression of CSF-1 receptors, with 50 J/m2 causing a significant reduction. Thus, UVB radiation interrupts CSF-1-mediated cell-cell interaction by a dual mechanism: downregulating CSF-1 production and abrogating CSF-1 receptor expression. Importantly, granulocyte/macrophage-colony stimulating factor receptor expression by XS cells was also inhibited by UVB radiation, once again, with 50 J/m2 producing significant inhibition. We propose that the resulting CSF-1 deficiency in epidermal microenvironment and unresponsiveness by dendritic cells to relevant growth factors may contribute to UVB-mediated loss of resident epidermal dendritic cells (i.e., Langerhans cells) in skin.

Fragmentation of the beta-subunit of human chorionic gonadotropin produced by choriocarcinoma.

When human chorionic gonadotropin (hCG) was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions with dithiothreitol (DTT), a smaller weight material (CTP'), in addition to the beta-subunit, could be detected by Western blot analysis using antiserum for hCG beta-carboxy-terminal peptide (CTP). The CTP' band was much more apparent with urinary hCG from a patient with choriocarcinoma than with that from normal pregnant women. Second-dimensional electrophoresis of the choriocarcinoma hCG (c-hCG) after reduction with DTT indicated that the CTP', Mr 25,000, was released from the beta-subunit. The carbohydrate structure of the CTP' was analyzed by affinity with lectin-peroxidase on a nitrocellulose membrane. The CTP' did not interact with Concanavalin A, but exhibited strong interaction with both RCA120 and Arachis hypogaea after removal of sialic acid, indicating that it was released as a fragment containing an O-linked sugar chain as was found in the hCG beta carboxy-terminal portion. Western blot analysis using the antisera for hCG alpha, hCG beta, and hCG beta-CTP showed that the CTP' contains not only the carboxy-terminal portion but also a part of the internal (core) portion of the beta-subunit molecule. This dissociation of the c-hCG beta was further supported by the presence of a faster moving component (FMC) which may correspond to the NH2-terminal side counterpart. The desialylated FMC could be detected by Concanavalin A and RCA120 but not by Arachis hypogaea, indicating that it contains N-linked rather than O-linked sugar chains. The FMC does not contain any of the epitopes for the antisera examined in Western blot. These results indicate that the beta-subunit of the choriocarcinoma urine hCG has an unusual site which is dissociated into two components of Mr 25,000 (CTP') and Mr 18,000 (FMC) by DTT reduction.

The role of CD4+ and CD8+ cells in normal F1 hybrid host in the resistance to lethal graft-versus-host disease induction by transfer of parent spleen cells.

Transfer of a certain number of C57BL/6 (B6) spleen cells into (BALB/cxB6)F1 (CB6F1) nu/nu mice, which are deficient in T cells, causes lethal graft-versus-host disease (GVHD) in the recipients. However, when normal CB6F1 mice are used as recipients, lethal GVHD does not occur. Using this lethal GVHD system, we investigated which roles CD4+ and CD8+ T cells play in the resistance to lethal GVHD induction by parent cell transfer in the normal F1 hybrid host. Lethal GVHD induction by B6 spleen cells in CB6F1 nu/nu mice was blocked by prior reconstitution of the recipients with normal syngeneic spleen cells. In addition, all nu/nu mice reconstituted with syngeneic CD8+ spleen cells developed lethal GVHD, whereas none of the nu/nu mice reconstituted with CD4+ cells did. Both spleen weight and number of spleen cells in the former prominently decreased in contrast to the slight increase (peak at 15 weeks) seen in the latter after transfer of donor spleen cells. H-2Dd- Thy1.2+ cells, which are considered to derive from donor B6 T cells, existed in the spleen from the CD4+ spleen cell-reconstituted GVHD mice, peaking at 5 weeks then gradually decreasing after transfer of donor cells. However, they disappeared in the normal spleen cell-reconstituted GVHD mice 5 weeks later. These findings suggest that CD4+ cells in the normal F1 hybrid host play a critical role in the resistance to lethal GVHD induction by parent spleen cell transfer, although CD8+ cells are required for the prompt elimination of donor cells.

Thalidomide increases both REM and stage 3-4 sleep in human adults: a preliminary study.

Polysomnography was used to assess the effect of thalidomide on human sleep. This compound significantly increased the time spent in REM and stage 3-4 sleep as compared with placebo. On the other hand, thalidomide significantly decreased the time spent in stage 1, while the time spent in stage 2 was unchanged. The effect of thalidomide on REM and stage 3-4 sleep is unique as compared with other hypnotics. Although the mode of action of this compound is unknown, further studies on thalidomide should help in our understanding of the mechanisms of sleep regulation.

Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC).

In this study, we evaluated the clinical usefulness of ProGRP and NSE for diagnosis and prognosis of small-cell lung cancer (SCLC). Serum levels of ProGRP and NSE were determined in 108 healthy subjects, 103 patients with benign pulmonary diseases, 142 with non-small cell lung cancer (NSCLC), and 114 with SCLC. Sensitivity of ProGRP in diagnosis of SCLC was significantly higher than that of NSE (64.9 vs. 43.0%, P < 0.001). The difference was substantial in patients with limited disease (56.5 vs. 20.3%, P < 0.001). However, 11 of 40 SCLC patients with normal levels of serum ProGRP (27.5%) showed elevated levels of serum NSE. In the SCLC patients receiving chemotherapy, the CR rate in patients with elevated NSE levels was significantly lower than in patients with normal levels of NSE (18.5 vs. 61.7%, P < 0.001). Elevation of both ProGRP and NSE was a poor prognostic factor, and patients with elevated levels of either ProGRP or NSE showed shorter survival than those without. From multivariate analysis, NSE was found to have a greater effect on survival of SCLC patients than ProGRP. These findings indicate that ProGRP is more sensitive than NSE for diagnosis of SCLC, while NSE is superior to ProGRP as a prognostic factor. In conclusion, both ProGRP and NSE are useful tumor markers and they have a complementary role for each other in diagnosis and prognosis of SCLC.

A case-control study of lung cancer screening in Okayama Prefecture, Japan.

The effectiveness of lung cancer screening in reducing mortality still remains uncertain. In order to evaluate the efficacy of lung cancer screening, a case-control study was conducted in Okayama Prefecture, Japan. The study area consisted of 34 municipalities where a population-based lung cancer screening had been conducted. Chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. The cases analyzed in this study consisted of 412 individuals aged between 40 and 79 who died of lung cancer. A total of 3490 controls, two to ten for each case matched by gender, year of birth, and living district were randomly collected. Screening histories of cases were compared with those of and matched controls for the identical calendar period prio to diagnosis of the case. Smoking adjusted odds ratio (OR) of death from lung cancer for screened individuals versus unscreened, within 12 months before diagnosis, was calculated as 0.59 (95% confidence interval: 0.46-0.74; P=0.0001). The OR for women (0.39, 95% confidence interval: 0.24-0.64) was lower than that for men (0.67, 95% confidence interval: 0.51-0.87), although both were statistically significant. These results suggest that lung cancer screening contributes to reducing lung cancer mortality by 41%.