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Pupae of the painted lady butterfly Vanessa cardui exhibit pupal color polyphenism consisting of white, dark and intermediate types. We investigated environmental factors affecting pupal coloration and the physiological mechanisms underlying the control of pupal color polyphenism in this species. Over 80% of larvae reared at 16 degrees C developed into pupae of dark types, whereas over 82% of larvae at 32 degrees C developed into pupae of white types irrespective of long/short-day photoperiod conditions. When mature larvae reared at 32 degrees C were ligatured between thoracic and abdominal parts at three different pharate pupal stages, all of the head-thoracic parts developed into white pupae regardless of pupal stage, but all abdominal parts ligatured at the early pharate pupal stage only developed into dark pupae. These results indicate that temperature during larval stages is an important element affecting pupal coloration as an environmental cue in V. cardui, and that a factor(s) inducing white pupae is released from head-thoracic parts under conditions of high temperature. Additionally, when ligatured abdomens destined to develop into dark pupae were treated with crude extracts prepared from the central nervous system, all of the ligatured abdomens developed into white pupae at a level dependent on dose and pupal stage. These results suggest that the factor inducing white pupae is a key molecule controlling pupal color polyphenism in V. cardui.

Background Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy. Materials and methods We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. Results EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers. Conclusions EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers.

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of tyrosine kinase. A previous report has suggested that overexpression of ErbB3 protein was associated with lung cancer recurrence. Other reports suggested that high ErbB3 protein expression was associated with shorter survival in advanced non-small-cell lung carcinomas (NSCLC). The relationship between the erbB3 mRNA expression and EGFR mutation has not been reported. In this study, we have investigated the erbB3 mRNA levels in reference to clinicopathologic data and EGFR mutation status in Japanese lung cancer specimens.This study included 192 surgically removed NSCLC cases operated at Nagoya City University Hospital. The erbB3 mRNA levels were quantified by real-time polymerase chain reaction using LightCycler (Roche Molecular Biochemicals, Mannheim, Germany).The erbB3/glyceraldehydes-3-phosphatate dehydrogenase levels were significantly higher in female than in male (P0.0001), higher in nonsmoker than in smoker (P = 0.0007), higher in adenocarcinoma than in other types of lung cancers (P0.0001), and higher in well-differentiated than in less-differentiated subtypes (P = 0.0304). The erbB3/glyceraldehydes-3-phosphatate dehydrogenase levels were significantly higher in patients with EGFR gene mutation than in patients without mutation (P = 0.0124).The present study suggests that increased expression of erbB3 may play an additional role in NSCLC especially in female, nonsmoker, adenocarcinoma, and with EGFR gene mutation. Further studies on large sample sizes would help to determine if erbB3 expression is a clinically useful tool to further define patients who will benefit from EGFR TKIs.

Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Recently, erbB4 kinase domain mutations were reported in Korean patients with lung cancer. We hypothesized that erbB4 mutations correlate with clinicopathologic features of lung cancers.The presence or absence of erbB4 kinase domain mutations was analyzed by reverse-transcription polymerase chain reaction amplification and direct sequencing in 105 surgically treated non-small-cell lung cancer cases from Nagoya City University Hospital. Sixty-three adenocarcinoma cases were included. The EGFR mutation status for these 105 samples were already reported. We have investigated erbB4 expression status by immunohistochemistry in 40 non-small cell lung cancer cases.ErbB4 mutation was not found in 105 patients with lung cancer. The EGFR mutation status was significantly correlated with sex (women, 74.2% vs. men, 9.5%; P0.0001), smoking status (never-smokers, 68.8% vs. smokers, 11%; P0.0001), pathologic subtype (adenocarcinoma, 44.4% vs. non-adenocarcinoma, 4.8%; P0.0001), and differentiation status of the lung cancer (well-differentiated, 47.4% vs. others, 14.8%; P = 0.0004). We detected ErbB4 protein positivity in 20 samples. The ErbB4 protein status was not significantly correlated with sex (women, 28.6% vs. men, 54.5%; P = 0.4075), smoking status (never-smokers, 69.4% vs. smokers, 16.9%; P0.0001), pathologic subtype (adenocarcinoma, 46.2% vs. nonadenocarcinoma, 51.9%; P0.9999), or differentiation status of the lung cancer (well-differentiated, 54.5% vs. others, 48.3%; P0.9999).Thus, erbB4 mutations are rare in Japanese people with lung cancer and of limited value for molecular-targeted therapy.

Purpose Human MOB1 ( hMOB1 ) is a recently isolated gene that is a human homologue of the Schizosaccharomyces mitotic checkpoint gene MOB1 . The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes, events associated with tumor progression. We hypothesized that hMOB1 might be expressed in non–small-cell lung cancer (NSCLC). Patients and Methods We attempted to determine the influence of hMOB1 expression on clinicopathologic features in patients with NSCLC who had undergone surgery. Expression of hMOB1 messenger RNA (mRNA) was evaluated by reverse transcription-polymerase chain reaction in 60 NSCLCs and adjacent histologic normal lung samples using LightCycler®. Results Human MOB1/glyseraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the tumor of lung cancer tissue (3.347 ± 4.306) compared with normal lung tissue (4.833 ± 4.306; P = 0.0437), although 22 of 60 lung cancer tissue samples had > 1 tumor-normal ratio of MOB1/GAPDH mRNA expression. There was no relationship between hMOB1 gene expression and age, sex, pathologic stages, or pN status. However, decreased hMOB1/GAPDH expression was especially seen in pT1 lung cancer (tumor-normal ratio; 0.318 ± 0.328) when compared with pT4 lung cancer (1.915 ± 1.895; P = 0.0362). Conclusion The decreased expression of hMOB1 mRNA might be the early phase phenomenon for tumor invasion from NSCLC. Alternatively, loss of mitotic checkpoint might play a role in oncogenesis for lung cancer.

ObjectiveThe presence of epidermal growth factor receptor (EGFR) mutations has been reported to predict the response to gefitinib in pulmonary adenocarcinoma patients. A retrospective analysis was conducted to identify the correlation between computed tomographic findings of the nodules and EGFR status.Patients and MethodsComputed tomographic findings of 38 patients with peripheral pulmonary adenocarcinoma with EGFR mutations were reviewed and compared with those of 42 peripheral pulmonary adenocarcinoma patients with wild-type EGFR.ResultsMutations were found significantly more frequently among women (28 of 45 women versus 10 of 35 men) and among non-smokers (31 of 47 non-smokers and 7 of 33 smokers). The L858R mutation was found in 18 cases. Several types of deletion mutants in exon 19 were found in 18 cases. The nodules with EGFR mutations (2.5 ± 1.0 cm) were significantly smaller in diameter than those in the wild-type group (3.1 ± 1.9 cm). Ground glass opacity (GGO) was more often observed in the mutation group (28 of 38) than in the wild-type group (24 of 42), but the difference was not statistically significant. When mutations were analyzed with reference to both the tumor size and GGO ratio, patients with a tumor ≤3 cm and a GGO ratio ≥50% often had EGFR mutations, and most (10 of 12) were expressed in female patients. No male adenocarcinoma patients with a tumor larger than 4.0 cm had EGFR mutations.ConclusionsEGFR mutations were found most frequently in small peripheral adenocarcinomas with a GGO ratio ≥50%, especially among women. These factors may be useful in deciding therapeutic strategies for adenocarcinomas when resection or biopsy is not feasible.

Diapause pupae of the swallowtail butterfly Papilio xuthus L. exhibit diapause-green, orange and brownish-orange color polymorphism. Development of orange pupae involves a neuroendocrine factor inducing orange pupa (Orange-Pupa-Inducing Factor, OPIF), which is secreted from the head–thoracic region during late pharate pupal stages, in particular from the ganglia of short-day animals located posteriorly from the second thoracic ganglion2 (TG2). This report describes certain properties of OPIF using bioassays involving ligated abdomens of short-day pharate pupae. Localization of OPIF in the central nervous system of short-day larvae indicated that it was present predominantly in TG2, thoracic ganglion3 (TG3) and abdominal ganglion1 (AG1) complexes. OPIF activity in TG2,3–AG1 complexes was over two times higher than in the more posteriorely located ganglia. The developmental profile of OPIF in last instar short-day larvae revealed that OPIF activity in larval ganglia posterior to TG2 became gradually higher as larval growth proceeded, suggesting that OPIF might be accumulated in TG2,3–AG1–7 complexes as larvae prepare for pupal molting. Furthermore, ligated abdomens of short-day larvae developed into pupae of an orange type when a 2% NaCl extract containing OPIF prepared from TG2,3–AG1–7 complexes of long-day larvae was injected into ligated abdomens of short-day pharate pupae, indicating that OPIF is also present in long-day larvae. Additionally, a biochemical investigation using gel filtration chromatography showed that the molecular weight of OPIF was about 10 kDa.

Background Endoscopic thoracic sympathectomy has been considered an effective treatment for palmar hyperhidrosis. However, the extent of resection has not been determined in terms of efficacy and complications. We compared the efficacy and complications of 2-ganglion and single-ganglion resection in patients with palmar hyperhidrosis. Methods From 1995 to 2000, 75 patients underwent resection of thoracic ganglion T2 and T3. From 2000 to 2003, 67 patients underwent resection of only the T2 ganglion. Eighty of the 142 patients (56%) answered a detailed questionnaire, the results of which were analyzed. Results Gender, age, family history, and distribution of sweating were similar in both groups. Recurrence rates 1 and 2 years after endoscopic thoracic ganglionectomy were between 0% and 3% in T2 and T3 resection, and between 15% and 19% in T2 resection only. In the combined T2 and T3 resection group, 100% of patients noticed compensatory sweating; in T2 resection, 90% of patients noticed compensatory sweating. As for rates of satisfaction, T2 and T3 resection was superior to T2 resection. Conclusions High recurrence rates of palmar hyperhidrosis after single-ganglion resection are reported in the present study. Two-ganglion resection is a superior surgical method to prevent recurrence of palmar hyperhidrosis.

We investigated the neuroendocrine regulation of the development of seasonal morphs in a bivoltine race (Daizo) of the silkmoth, Bombyx mori, by decerebration, the transplantation of brain-suboesophageal ganglion (Br-SG) complexes and the injection of active neuropeptides. When brains were removed from fresh pupae destined to develop into summer morphs (SD pupae) by embryonic and larval exposures to short days at low temperature, the pupae developed into autumn or intermediate morphs. However, in pupae destined to develop into autumn morphs (LD pupae), the operation did not show an effect on seasonal morph development. Br-SG complexes were excised from fifth-instar LD and fifth-instar SD larvae 2 days after larval ecdysis and were transplanted into the abdomen of SD larvae of the same age. The Br-SG complexes of LD larvae, but not the Br-SG complexes of SD larvae, shifted the host's seasonal morph development toward the autumn morph. Furthermore, when treated with crude pupal SGs extract and diapause hormone (DH), fresh SD pupae developed into autumn or intermediate morphs, respectively. Possibly the development of seasonal morphs in the silkmoth, B. mori, is regulated by a novel function of DH. Alternatively, DH may act on the imaginal wing disks at an earlier stage than on the ovaries.

Thymic carcinoids are classified into three categories: (1) nonsecretory tumors, (2) hormonal secretory tumors, and (3) tumors associated with multiple endocrine neoplasia type 1. We report a rare case with adrenocorticotropic hormone secreting thymic carcinoid with multiple endocrine neoplasia type 1. Radiologic examination showed an anterior mediastinal mass and a parathyroid tumor. Blood analysis revealed high levels of parathyroid hormone and adrenocorticotropic hormone. Urine cortisol and 17-hydroxycorticoids levels were also elevated. Extended thymectomy was performed. Subsequently adjuvant radiation therapy and parathyroid tumor resection were performed. A germline mutation of exon 7 in the multiple endocrine neoplasia type 1 gene was detected and a somatic mutation of exon 9 was demonstrated in the thymic tumor.

A neuropeptide from brain-suboesophageal ganglion (Br–SG) complexes of the silkmoth, Bombyx mori, shows summer-morph-producing hormone (SMPH) activity in the Asian comma butterfly, P. c-aureum. The SMPH-active peptide was extracted and demonstrated to be almost the same molecular size as bombyxin (4–5 kD), a nueropeptide which shows prothoracicotropic hormone (PTTH) activity when assayed in vitro with prothoracic glands (PGs) of 4th-instar B. mori larvae in vitro. A Sephadex G-50 fraction of 3–8 kD molecules prepared from Br–SG complexes of B. mori adults was applied to CM-, SP-, DEAE- or QAE- Toyoperal columns at pH 5.6 (or pH 6.9). The SMPH-activity could be separated from the PTTH-activity (or bombyxin) by subjecting a SMPH- and PTTH-active preparation of B. mori to anion-exchange chromatography at pH 6.9. By reversed-phase HPLC following an anion-exchange chromatography, SMPH-activity was recovered in two fractions of 40–45% acetonitril. Results demonstrate that the B. mori peptide showing the SMPH-activity in P. c-aureum is a different molecule than bombyxin.

Spring and summer morphs of Lycaena phlaeas daimio Seitz. are characterized by a wing colour of red and reddish brown, respectively. When newly ecdysed pupae destined to be summer or intermediate morphs (90 or 10%) by larval exposure to long days (long-day pupae) were decapitated or decerebrated, more than half of the operated pupae developed into intermediate and spring morphs (48 and 7%). But, in pupae destined to be spring, intermediate, or summer morphs (72, 22 or 4%) (short-day pupae) these operations did not produce any significant changes in the seasonal morph. Brains excised from newly ecdysed long-day pupae were transplanted into the abdomen of decapitated short-day pupae of the same age. The implants changed most recipients into summer and intermediate morphs (46 and 36%). However, when the brains of short-day pupae were used, no significant changes occurred in the seasonal morph. When long-day or short-day pupae were treated with 20-hydroxyecdysone just after pupation, they produced more reddish wings than those of the untreated or saline-treated controls. When the application was followed by chilling, already known to induce the reddish morph, the effects of both treatments are cumulative so that more reddish adults developed. The results indicate that the brain of long-day pupae secretes a factor causing the wing to be brownish. In the absence (or low titre) of the factor, most short-day pupae develop into spring or intermediate morphs. Furthermore, ecdysteroids make the wing more reddish, when applied to newly ecdysed pupae.

Seasonal morphs (spring and sumer forms) of Papilio xuthus L. are determined coincidentally with diapause and non-diapause in pupae by larval exposure to short days and long days respectively. The neuroendocrine principle underlying seasonal-morph determination was studied using surgical operations in P. xuthus . When recipient 0-day old or chilled diapause pupae were joined to donor 0-day old non-diapause pupae, the recipients developed into summer or intermediate morphs. When the same kinds of recipients used above were joined to 0-day old or chilled diapause pupae, there were no significant effects on the adult morph. In contrast, recipient non-diapause pupae all developed into summer morphs, regardless of groups of the type of donors. Furthermore, when the brain of 5th-instar larvae, pharate pupae or pupae, predetermined to be diapause, was transplanted into the abdomen of 0-day old, 30-day old or chilled diapause pupae, the recipients developed into summer or intermediate morphs. The results indicate that the brain of non-diapause pupae secretes a humoral factor producing the summer morph. In non-diapause pupae, the factor may be secreted at about the stage of larval-pupal ecdysis coincidentally with that of prothoracicotropic hormone.