A disintegrin and metalloproteinases (ADAMs) are members of the metzincin family of zinc-dependent metalloproteinases that play pivotal roles in the proteolytic degradation of the extracellular matrix for cell invasion. Few studies have investigated the ADAM subtypes that are expressed in first trimester trophoblast cells. The purpose of this study was to elucidate the differential expression profiles of ADAMs between first trimester villous trophoblast cells (VTs) and extravillous trophoblast cells (EVTs). We isolated EVTs from explanted human first trimester chorionic villi and investigated the mRNA expression levels of five members of the ADAM family (ADAMTS1, ADAMTS2, ADAM10, ADAM12, and ADAM17) using real-time PCR. Chorionic villous tips were defined as first trimester VTs. Of the differentially expressed ADAM genes between first trimester VTs and EVTs, ADAMTS1 was expressed at a significantly higher level in EVTs than in VTs. In contrast, both ADAM10 and ADAM12 were expressed at significantly higher levels in VTs than in EVTs. No differences were found in the mRNA levels of ADAMTS2 and ADAM17 between the two cell types. Moreover, we demonstrated that in VTs, the expression level of ADAM12 was significantly downregulated in the late first trimester (10-13 gestational weeks) compared to the middle first trimester (7-8 weeks). These results suggest that first trimester trophoblast cells express ADAM genes in cell type- and gestational age-dependent manners. Our data provide additional insight into the functions of ADAMs in the human placenta.

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Purpose: This study investigated the effects of direct hemoperfusion with polymyxin B-immobilized fibers (PMX-DHP) on respiratory impairment in endotoxemic pigs.
Materials and Methods: Thirteen anesthetized, mechanically ventilated pigs were divided into PMX-DHP (n=7) and control (n=6) groups. All pigs were hemodynamically monitored with the pulse index contour cardiac output (PiCCO) system (Pulsion Medical Systems, Munich, Germany) and infused intravenously with live Escherichia coli (LD50). In the PMX-DHP group, an arteriovenous extracorporeal circuit with a PMX column was applied for 30 to 150 minutes after endotoxin injection. We analyzed the laboratory data, arterial blood gas levels, and PiCCO variables (extravascular lung water [EVLW] and pulmonary vascular permeability index [PVPI]). Furthermore, we performed computed tomography of the chest in all pigs. The data were statistically analyzed with Student's t-test, the chi-square test, and the Mann-Whitney U-test.
Results: With PMX-DHP endotoxemia significantly decreased and blood pressure increased 150 minutes after endotoxin injection. PiCCO revealed more cases of decreased EVLW in the PMX-DHP group. PVPI increased after endotoxin infusion in both groups. Computed tomography showed improvements in the PMX-DHP group. The survival rate was greater in the PMX-DHP group (100%) than in the control group (71%).
Conclusion: PMX-DHP is effective for treating respiratory impairment and contributes to the decreased mortality rate in the endotoxemic pigs.

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Background: Patients with de novo stage IV and relapsed breast cancer are often treated with the same strategy. However, survival differences have recently been reported between the disease types.
Purpose: The aim of this study was to compare outcomes between de novo stage IV disease and relapsed disease and to discuss any differences in prognostic factors between them.
Patients and Methods: The subjects were 79 patients with de novo stage IV disease and 213 patients with relapsed disease treated at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, from October 2001 through November 2010. The Kaplan-Meier method was used to estimate overall survival (OS), and the Cox proportional hazards model was used to examine the association between metastatic disease and OS.
Results: The median follow-up period was 32 months for de novo stage IV disease and 34 months for relapsed disease. The median OS was 46 months and 43 months, respectively. No significant differences were evident. Identified prognostic factors were performance status and liver metastasis for de novo stage IV disease, and performance status, hormone receptor status, solitary bone metastasis, and disease-free interval for relapsed disease.
Conclusion: No differences in outcome were found between de novo stage IV disease and relapsed disease. However, their prognostic factors differed substantially and suggest that different treatment strategies may be warranted for metastatic disease in each type of breast cancer.

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Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritic and eczematous skin lesions and dermatitis that worsens under stressful conditions. However, the relation of these symptoms to an individual's stress sensitivity is not well understood. On the other hand, expression of the translocator protein (18 kDa) (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been used as a biological marker of trait anxiety and stress sensitivity. The present study was designed to address this issue by examining TSPO in patients with AD. Fifty-two patients with AD (30 male and 22 female) and 163 healthy volunteers (89 male and 74 female) participated in this study. State-Trait Anxiety Inventory (STAI) scores were significantly higher in patients with AD, especially male patients, than in healthy subjects. The expression of platelet TSPO, as determined with a binding assay with [³H] PK11195, was also significantly higher in patients with AD, indicating that AD is a stress-responsive disease. In genomic analysis using lymphocytes, a single-nucleotide polymorphism of the human TSPO gene at exon 4 (485G>A), which is presumably associated with an individual's stress sensitivity, showed significantly lower frequencies of G/G and higher frequencies of G/A in patients with AD than in healthy subjects. The severity of AD, as determined with the Scoring of Atopic Dermatitis index, was correlated with TSPO expression in male patients with the G/A phenotype. In conclusion, the present study provides new evidence that variation in the TSPO gene affects susceptibility to AD.

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Skin eruption with mild itching of the hands and feet developed in a man in his 90s 1 month after he was hospitalized following a traffic accident. Scabies was diagnosed in an attending nurse 3 months after the patient's hospitalization, and infection from the patient was suspected. Cornification of the patient's soles and marked hypertrophy of the nails of both feet were observed. After a large number of scabies mites were detected on microscopic examination, crusted scabies was diagnosed. The patient was given oral ivermectin, 6 mg, once per week for 3 weeks, and crotamiton topical ointment containing 30% benzyl benzoate was applied on the body from the neck down. However, because a large number of scabies mites were detected again on microscopic examination, the dose of ivermectin was increased to 12 mg and administered 3 times. One week after the sixth dose of ivermectin was administered, hemorrhagic scabs around the mouth and erosion of the tongue developed. Mucosal drug eruption was suspected, and eruptions around the mouth and on the tongue resolved within 1 week after ivermectin being discontinued. 1% gamma-benzene hexachloride ointment was applied topically on the body from the neck down once a week, crotamiton ointment containing benzyl benzoate was applied daily, and the hypertrophic parts of the nails were removed. The patient subsequently achieved a full recovery.

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A 75-year-old man was admitted to our hospital with dysphagia shortly after the onset of a brainstem infarction. Videofluorography indicated the presence of a Zenker's diverticulum with a bolus at the esophageal orifice; endoscopy 5 years earlier had not shown a Zenker's diverticulum and suggests that the diverticulum had formed because of an increase in the hypopharyngeal pressure caused by the brainstem infarction. Surgical excision successfully facilitated transport of the bolus to the esophageal orifice. In the present report, we describe a case of dysphagia caused by a Zenker's diverticulum following and associated with a brain infarction.

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A 64-year-old woman noticed a lump of the right breast and consulted our outpatient clinic. She had undergone multiple excisional biopsies of fibroadenomas in both breasts and mastectomy for invasive ductal carcinoma (IDC) of the left breast. After completing 5 years of treatment with adjuvant tamoxifen, she had undergone screening with annual physical examinations and occasional computed tomography. She was declared recurrence-free 13 years after breast cancer surgery, although lumps were detected in the right breast, probably due to fibroadenomas. Mammography, ultrasonography, and magnetic resonance imaging revealed that the lump was irregularly shaped, 2 cm in diameter, and adjacent to a fibroadenoma with macrocalcification. Two axillary lymph nodes were enlarged and suggestive of metastasis. A core needle biopsy revealed IDC of the right breast. She underwent a right partial mastectomy with axillary lymph node dissection. The IDC was 2 cm in diameter, of nuclear grade 2, and adjacent to a 0.7-cm fibroadenoma with a macrocalcification. The margins of the IDC close to the fibroadenoma were clearly demarcated by the fibrous capsule of the fibroadenoma. Four axillary lymph nodes were positive for metastasis. In the present case the presence of fibroadenoma might have interfered with the early detection of the contralateral IDC. The history of multiple excisions of fibroadenomas and mastectomy for breast cancer suggests an increased risk of contralateral breast cancer for the patient's entire life; therefore, regular annual follow-up, such as physical examinations and mammography, is recommended.

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The form and timing of the local recurrence of lung cancer can be unpredictable and unexpected. Pseudomesotheliomatous adenocarcinoma is a rare tumor that mimics malignant pleural mesothelioma both clinically and pathologically. Distinguishing pseudomesotheliomatous adenocarcinoma from malignant pleural mesothelioma on the basis of clinical findings can be difficult; therefore, a biopsy is usually required for diagnosis. Here we report on a 73-year-old Japanese man who presented with extensive dissemination along the pleural surfaces and clinical findings similar to those of pseudomesotheliomatous lung cancer 10 years after undergoing left upper lobectomy for lung adenocarcinoma. This report provides information that will help physicians establish an accurate diagnosis in similar cases.

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The patient, a 56-year-old woman, was found during routine checkup to have a disorder of hepatic function. Abdominal ultrasonography showed an ill-defined hypoechoic mass in the head and body of the pancreas; however, no blood-flow signal was observed within the tumor on Doppler ultrasonography. Abdominal computed tomography showed a low-density area in the arterial and portal venous phases. The lesion was visualized as an area of low signal intensity on both T1- and T2-weighted magnetic resonance images, whereas fluorodeoxyglucose positron emission tomography showed fluorodeoxyglucose accumulation in the tumor. Although a preoperative diagnosis was difficult to make, a rapid cytologic examination revealed evidence of a pancreatic endocrine tumor, and subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection was performed. Histopathological examination showed tumor cell nests scattered in abundant fibrotic tissue; the tumor cells had proliferated in a cord-like fashion and showed immunostaining for chromogranin A. Staining for fibroblast activation protein α was seen in the fibroblastic cells contained within the fibrous stroma surrounding the tumor cell nests, whereas both the fibroblastic cells in the tumor and those in the stroma showed a high rate of staining for thrombospondin. We presume that tumor-associated fibroblasts were involved in the fibrosis of the tumor stroma.

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