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Patient: Male, 70-year-old Final Diagnosis: Esophageal cancer Symptoms: Muscle pain • weaknes of lower limbs Medication: — Clinical Procedure: Biopsy of the skin Specialty: Rheumatology Objective: Unknown ethiology Background: Dermatomyositis (DM) is occasionally associated with malignancy, which is so-called cancer-associated myositis. The cancer screening in patients with dermatomyositis is an important clinical issue. That is because malignant disease underlying dermatomyositis is potentially life-threatening. Transcriptional intermediary factor 1γ (TIF1γ) antibodies (anti-TIF1γ Abs) are one of the myositis-specific autoantibodies, which are investigated as potential predictors of malignancy in patients with dermatomyositis. However, the etiology of anti-TIF1γ Abs generations in various cancer patients is not known. Case Report: A 70-year-old male patient was admitted for muscle pain and weakness in both legs. Erythematous on the face, eruption, and a V sign were also observed. Laboratory tests showed the elevation of creatine kinase, myoglobin, and aldolase. He was diagnosed as dermatomyositis. Cancer screening was performed, and esophageal cancer was detected in the lower esophagus. Despite the symptoms of dermatomyositis were improved with steroid, methotrexate, and radical esophagectomy, he died with esophageal cancer 3 years after the onset of dermatomyositis. TIF1γ is frequently overexpressed in cancer tissues. Therefore, some cancer patients without dermatomyositis could be positive for anti-TIF1γ Abs. We retrospectively analyzed anti-TIF1γ Abs in cancer patients (n=131). However, the screening of anti-TIF1γ Abs in cancer patients without dermatomyositis (n=130) showed there were no seropositive patients. Only this cancer-associated myositis patient was positive for anti-TIF1γ Abs. Conclusions: Our result suggested the generation of anti-TIF1γ Abs is specific for cancer associated myositis, not for tumorigenesis.

CASE REPORT, Fanconi syndrome (FS) is a rare disease characterized by a dysfunction of the proximal renal tubules. Drug-induced FS may be neglected or misdiagnosed, and most reported cases have occurred due to alkylating agents and platinum compounds. We encountered drug-induced FS in a patient with breast cancer using zoledronate. A 58-year-old woman underwent mastectomy for breast cancer at age 54. Two years later, bone metastases were detected and treated using a combination therapy of anastrozole and zoledronate. After 17 months, everolimus, exemestane, and zoledronate were prescribed. Then, she experienced hypocalcemia and proximal renal tubular dysfunction. FS induced by zoledronate was diagnosed, and zoledronate was immediately discontinued. This resulted in immediate and sustained improvement in renal function. In the past, three cases of zoledronate-induced FS were reported. All patients were prescribed zoledronate in combination with molecularly targeted drugs. Close monitoring of proximal tubular function is recommended for such patients.

ORIGINAL ARTICLE, Introduction: Tertiary hyperparathyroidism (THPT) refers to the development of hypercalcemia and hyperparathyroidism following a prolonged period of secondary hyperparathyroidism. THPT is most commonly observed in patients after successful kidney transplantation (KTx). The treatment guidelines for post-KTx THPT are still unclear; thus, this study aimed to examine patients who underwent parathyroidectomy (PTx) for THPT and to assess the effects of PTx on long-term graft function. Methods: We performed a retrospective study of patients who underwent PTx for THPT between 2009 and 2017 at our institution. Levels of serum calcium (Ca) and intact-parathyroid hormone (i-PTH) were measured before and after PTx (one day, one month, three months, six months, one year, and three years) to evaluate the effects of PTx. Estimated glomerular filtration rate (eGFR) was measured to investigate the effect on graft function after PTx. Results: Seven males and six females were included in this study. The post-PTx levels of serum Ca and i-PTH significantly decreased at one day compared with the pre-PTx levels (p < .001). The mean eGFR level decreased at three and six months after PTx. However, at one year post-PTx, the eGFR level had improved to the pre-PTx level. There was no recurrence or loss of graft function during a 58-month follow-up period. Conclusions: After PTx, the levels of serum Ca and i-PTH significantly improved. The level of eGFR tended to decrease within the first year. We recommend that clinicians follow-up closely with PTx patients during the first year post-PTx due to unstable renal function.

Case Report, Serum p53 antibody (s-p53-Abs) is induced by p53 overexpression in cancer cells. Therefore, residual cancer cells may be the cause of seropositivity even after radical surgery. Only few reports have evaluated perioperative changes and long-term monitoring of s-p53-Abs titers in patients with breast cancer. This case report presents long-term monitoring of s-p53-Abs titers in a patient with locally advanced breast cancer who developed recurrence in the central nervous system after radical surgery. The s-p53-Abs titer was monitored for 3 years during neoadjuvant chemotherapy and radical surgery in a 38-year-old woman with clinical stage IIB (T2N1M0) breast cancer. The levels of both the carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) were within the normal range, but s-p53-Abs test result (54.8 U/ml) was positive. Neither computed tomography nor bone scintigraphy showed any distant metastasis before treatment. The patient received neoadjuvant chemotherapy (epirubicin, 100 mg/m2; cyclophosphamide, 500 mg/m2; and fluorouracil, 500 mg/m2; followed by docetaxel, 75 mg/m2). One and a half year after surgery, s-p53-Abs results remained positive (5.66 U/ml), and brain metastasis was found. Despite resection for brain metastasis, s-p53-Abs titer remained high (5.88 U/ml), and carcinomatous meningitis was found. During the entire clinical course, although s-p53-Abs titers reflected the presence of residual cancer cells, both CEA and CA15-3 results were negative. The perioperative s-p53-Abs titer might be a useful marker for monitoring residual cancer cells in a patient with breast cancer. Recurrence in the central nervous system might be detected using s-p53-Abs monitoring.

Original Article, Background: Ras-like GTPases, RalA, and RalB, are members of the Ras superfamily of small GTPases. Their aberrant activation is a major cause of human tumorigenesis induced by oncogenic Ras. Serum anti-RalA antibodies (s-RalA-Abs) are induced in patients with esophageal carcinoma, but there have been no reports regarding their presence in patients with breast cancer. Methods: Serum samples from 100 patients with breast cancer and 73 healthy individuals were analyzed using an enzyme-linked immunosorbent assay system specifically developed for s-RalA-Abs. Positive rates of s-RalA-Abs and serum p53 antibodies (s-p53-Abs) were evaluated for two cut-off optical density values of 0.26 and 0.33 (i.e., the control mean+2 and 3 standard deviations), respectively. Results: Overall positive rates for s-RalA-Abs at the two cut-offs were 24% and 11%, respectively, with no statistically significant differences between stage I and stage II cancers. The positive rate increased significantly in a combination assay of s-p53-Abs with s-RalA-Abs, and s-RalA-Abs was shown to be inversely associated with s-p53-Abs. Conclusions: s-RalA-Abs in combination with s-p53-Abs may be a candidate serum antibody marker for breast cancer.

Eight years after surgical treatment for breast cancer, serum p53 antibody levels suddenly increased in a 67-year-old woman without recurrent signs of cancer. Early esophageal squamous cell carcinoma was detected by endoscopic screening. After endoscopic submucosal dissection was completed, serum p53 antibody levels decreased to be in the normal range. Serum p53 antibody monitoring can be helpful for early detection of not only recurrence of primary carcinoma but also development of metachronous carcinoma. This case is the first to monitor the changing titers of serum p53 antibody at the early phase of esophageal cancer progression into lamina propria mucosae until the disappearance of tumor cells.

研究報告, Original Articles, 精神障害を持った人が健康感を持って社会に参加するためには何が必要なのか，統合失調症者の西純一氏（仮名）の手記「精神障害を乗り越えて 40 歳ピアヘルパーの誕生」を読み，Schultz & Schkade の「作業適応過程モデル」を参考に回復段階ごとの日常生活の作業経験を分析した．本研究はナラティブ分析による質的研究である．Schultz & Schkade は，人は環境との交流の中で，「出来るようになりたい」と願い環境に働きかけ（習熟願望），環境は人に「できるように」期待，要求する（習熟要請）と述べた．その結果，その環境との交流で，人は作業に従事して環境に挑戦し，役割を得ると指摘した．西氏の場合，症状の強い段階では彼の環境は制限され，心身の保護とセルフケアが生活の主要な作業であったが，回復に従って環境からの要請が生産的なものへと移り変わり，それに応えて社会的な作業を通して環境に働きかけることで西氏は社会参加を実現させた．作業療法においては，健康感を持って社会に参加するように援助するためには，最大限の適応反応を導くことができる環境を見極めることが必要であることが示唆された．, The purpose of this study is to investigate how a person with mental problems participates in society and does or does not live with a sense of health and well-being. “The Birth of The 40-year-old Peer Helper Who Overcame a Mental Disorder” written by Mr. Junichi Nishi (pseudonym). A man with schizophrenia was studied using narrative analysis to understand his occupational experience in everyday life and in every recovery stage, using Schultz and Schkade’s occupational adaptation process model. Schultz and Schkade proposed that the person reaches out to the environment and has a desire for mastery in interactions with it (desire for mastery). In turn, the social environment expects or demands the person to master this skill (demand for mastery). As a result, Schultz and Schkade stressed that the person is challenging the environment while engaging in his or her occupation, gaining an occupational role. In the case of Mr. Nishi, in the symptomatic stage of the disease, his occupational demand from the social environment was limited, and mental and physical protection and self-care was his major focus in everyday life. However, for the sake of recovery, his occupational demand from his social environment expanded to include productive tasks. Thus, he challenged the environment, and realized social participation by performing tasks related to social work. In occupational therapy, in order to help the patient become an active participant in society, and gain a sense of health and well-being, it is necessary to determine the kind of environment that can lead to maximal adaptive responses.

Case Report, Serum p53 antibody (s-p53-Ab) is the most recently developed biomarker for breast cancer. Only a few studies have evaluated perioperative s-p53-Ab titers in patients with breast cancer. S-p53-Ab titers were monitored for over 4 years, during the perioperative period and after surgery, in a 75-year-old woman with clinical stage IIA (T2N0M0) breast cancer. The results of screening tests were negative for cancer antigen 15-3, carcinoembryonic antigen (CEA), and National Cancer Center-Stomach-439; only s-p53-Ab level (10.1 U/ml) was positive preoperatively. S-p53-Ab titer remained positive (9.1 U/ml) after radical surgery. Pathologic analysis of surgically resected specimens showed a stage IIB tumor (pT2N1M0). Two years postoperatively, CEA level had increased to 5.9 ng/ml. At this time, liver metastases were detected by computed tomography. Neither chemotherapy nor hormone therapy were effective against this recurrence, and the patient died 3 years after surgery. Perioperative s-p53-Ab titer was a useful marker for long-term monitoring of residual cancer cells in a patient with stage IIA breast cancer.

In patients with differentiated thyroid carcinoma (DTC), lung and bone metastasis sometimes occur. However, brain metastasis (BM) is extremely rare. Because most previous reports about BM from DTC included a relatively small number of cases, the clinical characteristics and outcomes of BM are still unclear. Between 1965 and 2013, among 961 patients who had died because of DTC, 24 patients were diagnosed with BM from DTC. One patient with BM from DTC is still alive. To identify the prognostic factors for longer survival after BM, the medical records of these 25 patients were retrospectively reviewed. The median age at BM diagnosis was 66 years. Typical symptoms associated with BM had appeared in 20 patients (80 %). The Karnofsky Performance Status (KPS) was good (≥70) in 10 patients and poor (≤60) in 15 patients. Seven patients had a single intracranial lesion of BM, 6 patients had 2 or 3 lesions, and 9 patients had 4 or more. Eleven patients did not receive any treatment for BM, and 14 patients underwent surgical resection, radiation therapy, or both. One-year and 5-year disease-specific survival rates were 28 and 10.6 %, respectively. Good KPS (≥70), small number of intracranial lesions (≤3), and treatment for BM were prognostic factors for long survival on univariate analysis (p

Purpose Paget disease of the breast is a rare cancer that originates from the nipple–areolar complex. It is often overlooked and misdiagnosed as benign chronic eczema of the nipple. We aimed to retrospectively verify whether blood flow analysis using Doppler sonography was useful for detecting the presence of Paget disease. Methods In this retrospective study, 12 patients with pathologically proven unilateral nipple eczematous lesions (seven with Paget disease and five with simple dermatitis) were included. Nipple blood flow signal was observed using Doppler sonography, and the detected blood flow signals were quantified using digitally recorded images. Quantified blood flow ratio and pathologically examined capillary density were evaluated between affected and unaffected nipples. Findings of mammography, grayscale sonography, and contrast-enhanced magnetic resonance imaging (CE-MRI) were reviewed. Results In patients with Paget disease, Doppler effects in the affected nipple were more clearly visible than those in the unaffected nipple. These effects were sufficiently visible to identify Paget disease. No obvious effects were observed in the affected and unaffected nipples of simple dermatitis. The quantified blood flow ratio and pathologically examined capillary density were significantly higher for the Paget lesion than those for the non-Paget lesion. The sensitivity of CE-MRI and Doppler sonography was markedly correlated, revealing blood flow changes in the nipple lesions of Paget disease. Conclusion Doppler sonography visualized the proliferation of blood vessels in Paget lesions. The visualization of increased nipple blood flow using Doppler sonography is a simple and low-cost method that provides useful data for identifying Paget disease during routine medical care.

Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options. While rationally-derived regimens are emerging from the results of recent gene profiling studies, TNBC is an angiogenesis-dependent malignancy, and antiangiogenic therapies have been examined energetically in this field. Antiangiogenic agents in combination with chemotherapeutic platinum compounds have shown some benefit in recent randomized control studies for the treatment of TNBC. These combinations could be more safe and efficacious in patients, when pharmacotherapy schedule is modified taking into account its tolerability.

Breast cancer-related lymphedema often causes cellulitis and is one of the most common complications after breast cancer surgery. Streptococci are the major pathogens underlying such cellulitis. Among the streptococci, the importance of the Lancefield groups C and G is underappreciated; most cases involve Streptococcus dysgalactiae subspecies equisimilis. Despite having a relatively weak toxicity compared with group A streptococci, Streptococcus dysgalactiae subspecies equisimilis is associated with a mortality rate that is as high as that of group A streptococci in cases of invasive infection because Streptococcus dysgalactiae subspecies equisimilis mainly affects elderly individuals who already have various comorbidities. An 83-year-old Japanese woman with breast cancer-related lymphedema in her left upper limb was referred to our hospital with high fever and acute pain with erythema in her left arm. She showed septic shock with disseminated intravascular coagulation. Blood culture showed positive results for Streptococcus dysgalactiae subspecies equisimilis, confirming a diagnosis of streptococcal toxic-shock syndrome. She survived after successful intensive care. To the best of our knowledge, this case represents the first report of Streptococcus dysgalactiae subspecies equisimilis-induced streptococcal toxic-shock syndrome in a patient with breast cancer-related lymphedema. Breast cancer-related lymphedema is a common problem, and we must pay attention to invasive streptococcal soft tissue infections, particularly in elderly patients with chronic disease.

Fetal thymus colonization is initiated before the vascularization of the thymus primordium. This prevascular colonization of the fetal thymus by T-lymphoid progenitor cells is guided by the coordination of CCR7- and CCR9-mediated chemokine signals. However, the intracellular signals that mediate the prevascular migration of T-lymphoid progenitor cells to the fetal thymus are unknown. Here we show that T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, DOCK2 and DOCK180. We found that the prevascular fetal thymus accumulation in vivo was significantly reduced in mice doubly deficient for DOCK2 and DOCK180 but not in mice deficient for either DOCK2 or DOCK180. Immature T-lymphoid cells from mice doubly deficient for DOCK2 and DOCK180 were defective in their in vitro migration towards fetal thymus lobes. The T-lymphoid progenitor cells generated in mice lacking DOCK2 and DOCK180 were capable of T-cell development after their transfer into a fetal thymus environment, and the impaired fetal thymus colonization in mice deficient for DOCK2 and DOCK180 was not as severe as that in mice doubly deficient for CCR7 and CCR9. These results indicate that the combination of DOCK2 and DOCK180 plays a significant but not essential role in prevascular fetal thymus colonization.

The use of frame retractors for excisional biopsies of the breast is straightforward and can be performed by a single surgeon without assistance. In addition, since a surgical field is established around the lesion, it is possible to obtain a visual field large enough to permit highly reliable excision of the lesion. We discuss our experience with frame retractors in such surgical procedures. In ten patients with breast lesions that could not be conclusively diagnosed by aspiration cytology and needle biopsy, frame retractors were used to perform surgical biopsies under local anesthesia. Blood loss, duration of surgery, analgesic usage, and complications were assessed. In all cases, the amount of blood loss was low ; the mean duration from the start of anesthesia to wound closure was 41 minutes. In summary, our results show that frame retractors are extremely useful for excisional biopsies of the breast.

成人に発症した仙尾部腫瘍を2例経験したので報告する. 症例1は40歳, 女性で不正性器出血の精査中に仙尾部腫瘍と診断された. 症例2は27歳, 男性, 下血および腰痛を認め, 精査の過程で仙尾部腫瘍と診断された. 2症例ともに術前画像検査から良性腫瘍の可能性が高いと判断し, 経仙骨的に腫瘍摘出術を施行した. 病理学的診断は症例1がepidermoid cyst, 症例2が成熟奇形腫であった. 成人の仙尾部腫瘍は比較的稀であるが, 悪性化の報告もある. 経仙骨的に完全切除した上で, 詳細な病理学的検索を行い厳重な経過観察が重要である.

Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE.

Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death. A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents. We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy. The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years. Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section. Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver. No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified. At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases. This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation.

Thymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell development. However, molecules guiding thymus colonization and their roles before and after thymus vascularization are unclear. Here we show that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective prevascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal Vγ3+ γδ T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent thymic primordium, revealing the role of the adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization.

Epidemiological studies suggest that diesel exhaust particles (DEP) contribute to an increase in allergic diseases. To assess the effects of DEP on the central immune system, mice were exposed to DEP by intraperitoneal (IP) administration. Exposure to DEP resulted in severe thymic involution accompanied by a reduction in the number of thymocytes, especially in cortical CD4+CD8+ double positive and double negative subsets. Core carbon particles associated with a mixture of chemical compounds in DEP did not appear to be responsible for the DEP-induced thymic involution because carbon graphite does not affect neither the number nor the CD4/CD8 profile of thymocytes. Extraction of DEP by ether, acidic and basic solvents showed that several independent fractions including the neutral ether fraction, which contains polycyclic aromatic hydrocarbons (PAH), induced thymic involution. Among major PAH components of DEP, benzo[b]fluoranthene (BbF), benzo[a]pyrene (BaP), and benzo[k]fluoranthene (BkF) were very potent...

Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the medulla for further differentiation and selection. However, it is unknown how this cortex–medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the medulla. These mutant mice are defective in forming the medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the medulla. CCR7-dependent cortex–medulla migration of thymocytes plays a crucial role in medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes.

The thymus is composed of multiple stromal elements comprising specialized stromal microenvironments responsible for the development of self-tolerant and self-restricted T cells. Here, we investigated the ontogeny and maturation of the thymic vasculature. We show that endothelial cells initially enter the thymus at E13.5, with PDGFR-β(+) mesenchymal cells following at E14.5. Using an allelic series of the thymic epithelial cell (TEC) specific transcription factor Foxn1, we showed that these events are delayed by 1-2 days in Foxn1 (Δ/Δ) mice, and this phenotype was exacerbated with reduced Foxn1 dosage. At subsequent stages there were fewer capillaries, leaky blood vessels, disrupted endothelium - perivascular cell interactions, endothelial cell vacuolization, and an overall failure of vascular organization. The expression of both VEGF-A and PDGF-B, which are both primarily expressed in vasculature-associated mesenchyme or endothelium in the thymus, were reduced at E13.5 and E15.5 in Foxn1 (Δ/Δ) mice compared with controls. These data suggest that Foxn1 is required in TECs both to recruit endothelial cells and for endothelial cells to communicate with thymic mesenchyme, and for the differentiation of vascular-associated mesenchymal cells. These data show that Foxn1 function in TECs is required for normal thymus size and to generate the cellular and molecular environment needed for normal thymic vascularization. These data further demonstrate a novel TEC-mesenchyme-endothelial interaction required for proper fetal thymus organogenesis.

A 39-year-old premenopausal nulliparous woman presented with severe pain in her right breast, bleeding and pus-like discharge, and a deep ulcer approximately 18 cm in diameter.Contralateral breast metastasis, bilateral axillary lymph node metastases, and multiple lung and bone metastases were detected on computed tomography.Five years previously she had undergone surgery for ovarian cancer and had prematurely discontinued adjuvant chemotherapy because of side effects. Following the administration of pain control, the patient received trastuzumab(Tr)plus vinorelbine(VNR)for her breast cancer as first-line therapy to avoid hair loss.The ulcer on her right chest wall underwent complete epithelialization and the patient's performance status improved from 3 to 0.The pus-like discharge, pain, bleeding, and odor from the breast resolved completely, and 5 months later, her quality of life had improved.The lung metastases also resolved completely.No adverse affects, including hematotoxicity and hair loss, were seen until treatment failure 12.5 months later. Second-line and third-line treatments were performed, but brain metastases developed, and the patient's overall condition deteriorated because of the development of ileus of unknown etiology.She died 21 months later.The patient received all therapies on an outpatient basis. Combination therapy using Tr and VNR is superior in safety and tolerability, and has been considered an option for first-line treatment of metastatic, locally advanced HER2-positive breast cancer.

The thymus has been implicated as a possible site of origin that triggers autoimmunity in myasthenia gravis (MG). Although several groups have suggested that the decrease in the number of regulatory T (Treg) cells contributes to the onset of MG, the exact role of Treg cells in MG remains unclear. To address this point, we examined the number and distribution of Treg cells in a large number of patients with MG.Immunohistofluorescence analysis of Foxp3 along with CD4 and CD8 was performed in thymic sections of MG (+) (n = 24) and MG (-) patients (n = 27). Circulating CD4(+)CD25(+) cells in the peripheral blood of patients with MG (n = 15) and age-matched healthy subjects (n = 15) were also analyzed.Foxp3(+)CD4(+)CD8(-) cells were predominantly found in the thymic medulla and their number declined with age. There was no significant difference in the number or the distribution of Foxp3(+)CD4(+)CD8(-) cells in the thymus between MG (+) and MG (-) patients. The number of circulating CD4(+)CD25(+) cells in the peripheral blood of patients with MG was not significantly altered compared to that in healthy subjects.The cellularity of Treg cells in the thymus and circulation is not diminished in patients with myasthenia gravis.

The cover image is a colour inverted figure taken from Role of DOCK2 and DOCK180 in fetal thymus colonization by Lei et al. (pp. 2695–2702). By co-staining sections of frozen embryos for CD45 and keratin, the authors elegantly show that a combination of DOCK2 and DOCK180, two closely related CDM family molecules, plays a significant role in prevascular fetal thymus colonization.

The major red carotenoids in autumnal, colored leaves were analyzed in seven species and one variety that belong to two families of gymnosperms. The red carotenoids in leaves of all species and variety were rhodoxanthin, which was separated into three geometric isomers, (6Z, 6′Z)-rhodoxanthin, (6Z)-rhodoxanthin and (all E)-rhodoxanthin. The effects of daylight intensity on the content and composition of the leaf pigments of autumnal coloration were studied with leaves ofCryptomeria japonica (evergreen) andTaxodium distichum (deciduous) grown under different grades of shade. Histological observation showed that many reddish particles of rhodoxanthin were observed inside chromoplasts on the sunny side of a leaf at the early stage of coloration and that the content of the reddish particles was decreased toward the shady side from the sunny side of a leaf. The transition from chloroplasts to chromoplasts was observed and cells at different stage of coloration independently existed in the mesophyll tissue of a leaf. The content of rhodoxanthin became maximum when the daylight intensity was 4.1–7.4 MJ m−2 day−1 and the daily mean temp. was below 8.1 C inCryptomeria, and 3.1–8.3 MJ m−2 day−1 and 13.4 C inTaxodium.

Various treatments for hepatic metastasis of gastric cancer have been attempted, but problems remain with respect to long-term effectiveness and recurrence. Case reports have indicated the tumor regression effect of polysaccharide K(PSK)combined with chemotherapy, and meta-analysis has shown that PSK combined with chemotherapy improves the prognosis compared to chemotherapy alone. However, marked improvement of disease following PSK administration is rarely reported. We report a case of hepatic metastasis of gastric cancer in which low-dose UFT and PSK therapy resulted in regression of metastatic hepatic lesions and improvement of tumor markers. A 78-year-old man had synchronous hepatic metastasis of gastric cancer. Gastrectomy and microwave coagulation therapy using Microtase were conducted, followed by postoperative adjuvant chemotherapy with UFT 300 mg/day. Recurrences of metastatic hepatic lesion and new hepatic lesion were observed 6 months after surgery. Addition of PSK to UFT chemotherapy was selected as the treatment for recurrences, resulting in disappearance of the hepatic lesions and normalization of tumor markers. The patient is alive without recurrence at this writing, 38 months after surgery.

TCR ligation by the self-peptide-associated MHC molecules is essential for T cell development in the thymus, so that class II MHC-deficient mice do not generate CD4+CD8− T cells. The present results show that the administration of anti-TCR mAb into class II MHC-deficient mice restores the generation of CD4+CD8− T cells in vivo. The CD4 T cells were recovered in the thymus, peripheral blood, and the spleen, indicating that the anti-TCR treatment is sufficient for peripheral supply of newly generated CD4 T cells. Unlike peripheral CD4 T cells that disappeared within 5 wk after the treatment, CD4+CD8− thymocytes remained undiminished even after 5 wk, suggesting that CD4 T cells in the thymus are maintained separately from circulating CD4 T cells and even without class II MHC molecules. It was also found that the mass of medullary region in the thymus, which was reduced in class II MHC-deficient mice, was restored by the anti-TCR administration, suggesting that the medulla for CD4+CD8− thymocytes is formed independently of the medulla for CD4−CD8+ thymocytes. These results indicate that in vivo anti-TCR treatment in class II MHC-deficient mice restores the generation of circulating CD4 T cells and optimal formation of the medulla in the thymus, suggesting that anti-TCR Ab may be useful for clinical treatment of class II MHC deficiencies.

Expression of four BMP antagonist genes, noggin, chordin, gremlin and Follistatin, was examined during chick feather development. Although expression of noggin and chordin was not detected, gremlin and Follistatin were expressed differentially in feather buds. The differential expression patterns of gremlin and Follistatin change dynamically from the nascent inter-feather bud region to the posterior domain of the feather bud.