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This study examined the relationship between skin physiological indices and pressure ulcers in elderly people. The subjects were 55 bedridden elderly Japanese patients with a median age of 85 years. The following parame-ters were measured using non-invasive devices: skin surface temperature, moisture content in the stratum corneum, moisture content in the dermis, transepidermal water loss as an index of skin barrier function, skin erythema and skin elasticity. The sacral and 2 heel areas were observed as sites predisposed to pressure ulcers. Within one month after measuring the skin physiological indices, we confirmed pressure ulcers of National Pressure Ulcer Advisory Panel classification Stage II or worse based on medical records. Among the 55 patients, 4 (7.3%) prospectively developed a total of 5 pressure ulcers within 16 days. Only the skin erythema score was significantly higher with than without pressure ulcers (p < 0.001). We performed a binary logistic regression analysis and confirmed a significant relationship between pressure-ulcer development and the level of erythema (odds ratio = 1.026; 95% confidence interval: 1.011-1.042). Skin erythema increased before the development of pressure ulcers. Taken together, our results show that the high skin erythema score can be a predictive indicator of pressure ulcers.

Background Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). Methods This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The ‘malaria indicator questionnaire’ (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. Results There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p

Background Malaria is one of the most prevalent and deadliest illnesses in sub-Saharan Africa. Despite recent gains made towards its control, many African countries still have endemic malaria transmission. This study aimed to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory Water, Sanitation and Hygiene (WASH) Action programme. Methods Mixed method research was conducted in two semi-rural towns, Mbanza-Ngungu (a WASH action site) and Kasangulu (a WASH control site) in DRC between 1 January 2017 through March 2018, involving 625 households (3,712 household members). Baseline and post-intervention malaria surveys were conducted with the use of World Bank/WHO Malaria Indicator Questionnaire. An action research consisting of a six-month study was carried out which comprised two interventions: a community participatory WASH action programme aiming at eliminating mosquito breeding areas in the residential environment and a community anti-malaria education campaign. The latter was implemented at both study sites. In addition, baseline and post-intervention malaria rapid diagnostic test (RDT) was performed among the respondents. Furthermore, a six-month hospital-based epidemiological study was conducted at selected referral hospitals at each site from 1 January through June 2017 to determine malaria trend. Results Long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%); 24% of households did not use any measures. Baseline malaria survey showed that 96% of respondents (heads of households) reported at least one episode occurring in the previous six months; of them only 66.5% received malaria care at a health setting. In the Action Research, mean incident household malaria cases decreased significantly at WASH action site (2.3 ± 2.2 cases vs. 1.2 ± 0.7 cases, respectively; p Conclusion This research showed high prevalence of positive malaria RDT among the responders and high household malaria incidence, which were reduced by a 6-month WASH intervention. DRC government should scale up malaria control strategy by integrating efficient indoor and outdoor preventive measures and improve malaria care accessibility.

Objective Gastrointestinal dysmotility in critically ill patients is important as enteral nutrition is crucial. However, normal gut motility is impaired under conditions of critical illness subsequent to severe insult. Interstitial cells of Cajal (ICC) form an extensive network associated with the myenteric plexus in the enteric nervous system. There are few reports about ICC distribution in critically ill patients. The aim of this study was to evaluate ICC in critically ill patients. Methods Postmortem colon harvest was obtained from critically ill patients. Control specimens were obtained from patients without bowel movement problems who underwent hemicolectomy. The tissues were stained with c-Kit for ICC. The number of ICC was identified by counting from 10 high-power fields (HPFs). Results Specimens from six patients were analyzed and compared with those from six control patients. All patients had abnormalities of crypt architecture and inflammatory cell infiltrations. Mucosal thickness tended to be lower in the critically ill patients than in the controls (147 ± 47 versus 231 ± 127 μm; P = 0.15). Muscle layer thickness tended to be higher in the critically ill patients than in the controls (494 ± 163 versus 394 ± 258 μm; P = 0.44). ICC in the critically ill patients were almost depleted in the colon compared with those in the controls. Significantly fewer ICC were present in the critically ill patients than in the controls (0.45 versus 7.25 cells/HPF; P Conclusions Critical illness is associated with diminished numbers of ICC in the colon. This finding could have implications for dysmotility in critically ill patients.

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

The preventive association of synbiotics therapy has not been thoroughly clarified in mechanically ventilated patients. The purpose of this study was to evaluate whether synbiotics therapy has preventive association against septic complications in ventilated critically ill patients.Critically ill patients who were mechanically ventilated were included in this retrospective observational study. Patients who received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) within 3 days after admission (denoted as synbiotics group) were compared with patients who did not receive synbiotics. The incidences of enteritis, pneumonia, and bacteremia were evaluated as clinical outcome. Enteritis was defined as an acute onset of diarrhea consisting of continuous liquid watery stools for more than 12 h. The confounding factors include APACHE II on admission, gender, the cause of admission and antibiotics.We included 179 patients in this study: 57 patients received synbiotics and 122 patients did not receive synbiotics. The incidences of enteritis were significantly lower in the synbiotics group compared with the control group (3.5% vs. 15.6%; p 0.05). The odds ratios for diarrhea-free days during the first 28 days for the synbiotics group as compared with the controls were 4.354 (95% confidence interval (CI), 2.407 to 7.877; p 0.001) in an ordinal logistic regression model with propensity scores. The odds ratios for pneumonia-free days during the first 28 days for the synbiotics group were 2.529 (95% CI, 1.715 to 3.731; p 0.001). The incidences of bacteremia did not have significant differences.Prophylactic synbiotics appeared to have preventive association on enteritis and pneumonia in mechanically ventilated critically ill patients.

Background Commensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis. Methods Sepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h. Results Seventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p

Purpose One of the pathophysiological processes in sepsis is endothelial dysfunction, which leads to disseminated intravascular coagulation (DIC). Syndecan-1 is a major structural component of the endothelium and plays a key role in endothelial function. The purpose of this study was to assess the value of syndecan-1 as a predictive marker for DIC in sepsis. Methods We performed a prospective observational study of patients with sepsis from February 2014 to July 2015. Serial change of hemostatic markers, anticoagulant and fibrinolytic markers (antithrombin, PAI-1), endothelial markers (syndecan-1, VCAM-1, E-selectin), and inflammatory markers (IL-1β, IL-6, IL-8, HMGB-1, histone-H3) were analyzed. Clinical data including APACHE II, SOFA, and DIC scores and 28-day mortality were also evaluated. Results During the study, 39 septic patients and 15 healthy controls were included. Syndecan-1 levels were significantly increased in the septic patients compared with the healthy controls. Of the septic patients, non-survivors had higher syndecan-1 levels than did the survivors on days 1, 2, and 4. Significant correlations on day 1 were found between syndecan-1 levels and APACHE II, SOFA, and DIC scores, hemostatic markers, IL-1β, IL-8, and PAI-1. Syndecan-1 levels on day 1 were also significantly higher in patients with than without DIC and had strong discriminative power for the prediction of both DIC development and subsequent mortality, with AUCs of 0.79 and 0.85, respectively. Conclusion Syndecan-1 levels were associated with not only the severity of illness and mortality but also DIC development in sepsis, suggesting that syndecan-1 could be a predictive marker of DIC.

Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.

The replenishment of adiponectin—an adipocyte-derived hormone with salutary health effects—has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.

Drug reaction can be one of the triggering factors either for exacerbation of pre-existing psoriasis or precipitation of psoriasis de novo. Herein, we report a case with psoriasiform drug eruption due to pravastatin, but it relapsed after discontinuance of the drug. Serial investigation of the histopathology and immunohistochemistry with anti-signal transducer and activator of transcription 3 (STAT3) revealed drug reaction-associated lesions intermingled with psoriasiform changes, which later predominated, suggesting a conversion into psoriasis de novo.

Proteins destined for the peroxisome matrix or membrane possess distinct targeting signals that engage signal sequence receptors to drive their transport to their final subcellular destination. Peroxisomal targeting signal 1 (PTS1) and 2 (PTS2) are well characterized as signaling the import from the cytosol into the peroxisomal matrix of soluble peroxisomal enzymes. The expression vectors of the enhanced green fluorescent protein (eGFP)-tagged alanine:glyoxylate aminotransferase (AGT) and deletion mutants were introduced into HeLa cells to identify the peroxisomal targeting signal of the AGT. Two sites of the targeting signals into peroxisome, an amino acid sequence containing 59-66 a.a. (8 amino acids) and 389-392 a.a. (4 amino acids, KKKL, but not KKL) on the AGT were clarified. In a three-dimensional structural model, their sites were separately located on the surface of the AGT protein.

Background: The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen’s original article was published in 1912. Methods: We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease. Results: Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35βH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas. Conclusions: Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis.

Background Activated mast cells enhance the uptake of mast cell–derived proteoglycan–low-density lipoprotein complexes by macrophages. Objective We sought to investigate mast cell contribution to the pathogenesis of xanthoma. Methods Twenty cases of xanthelasma palpebrarum and 6 cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results Xanthelasma lesions contained up to 5-fold more tryptase-stained mast cells than tuberous xanthoma lesions. Tuberous xanthoma lesions especially showed extensive staining of tryptase around mast cells and within some macrophages and foam cells. More than 99% of mast cells in xanthelasma lesions contained both tryptase and chymase. Approximately 60% of mast cells represented only tryptase in tuberous xanthoma lesions where the ratio of macrophages to tryptase-stained mast cells was extremely high (15:1) as compared with xanthelasma lesions (2:1). Limitations A change in mast cell phenotype has not been necessarily proven. Conclusion Mast cells are activated under the microenvironment in which macrophages predominate rather than mast cells, which thus reflects the clinical phenotypes of xanthoma lesions.

We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells.

A 15-year-old boy first noticed multiple firm papules on his right upper chest two years before presenting to our clinic. These papules were densely distributed and showed epidermal nevus-like linear arrangement at some sites. The number, size, and distribution of these papules remained unchanged for one year of our observation. The papules flattened leaving scars and did not recur within a year after one shaving abrasion using a scalpel. Histopathologically, epidermis of the papule displayed acanthosis with elongated rete ridges. Accumulation of mucin was apparent in the papillary and subpapillary dermis. In mucinous nevus, the origin of cells with nevoid proliferation is obscure. In contrast with common collagenous connective tissue nevus, it is hard to define the localized persistent mucin accumulation as a nevoid manifestation. The present case of mucinous nevus might be caused by significantly stimulated glycosaminoglycan synthesis in a kind of epidermal nevus without extreme hyperkeratosis.

Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.

Infrasternal mediastinoscopic single-incision surgery is a minimally invasive surgical option for patients with anterior mediastinal lesions. The main drawback of the procedure is difficult when handling the endoscopic instruments through the small infrasternal incision. Herein, we report our initial experience with use of the procedure in 2 patients with bronchogenic cysts in the anterior mediastinum. We found that use of an SILS Port, now widely available for single-incision laparoscopic surgery, can decrease the difficulty of this approach.

We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement.

Peripancreatic head cancer often causes obstructive jaundice and duodenal obstruction, which reduces the quality of life and hinders the administration of anti-cancer drugs. Here, we report 4 cases of double bypass surgery( biliary and gastric) for the treatment of inoperable peripancreatic head cancer. The patients' ages ranged from 64 to 72 years. Two patients had pancreatic head cancer and 2 had ampullary cancer. No postoperative morbidity was observed and all 4 patients resumed oral intake within 5 days after surgery and began receiving chemotherapy within 1 month after surgery. There was immediate relief of biliary obstruction in all 3 patients with obstructive jaundice. None of the patients experienced recurrence of obstructive jaundice requiring biliary drainage. Two patients who died of cancer were able to consume food orally just before they died. Although bypass surgery is more invasive than endoscopic stenting, it may be safe and useful not only for palliation, but also for induction or continuation of chemotherapy.

A 53-year-old female developed erythema elevatum diutinum (EED) twelve years after the onset of rheumatoid arthritis. The arthritis had been well controlled for the last several years. Annular purpuric macules were characteristically complicated by common nodular and plaque lesions. Both leukocytoclastic vasculitis and fibrosis were observed in the macular lesions, indicating that the lesions were a manifestation of an early phase of EED. Both types of skin lesions disappeared with treatment with dapsone. They have not relapsed for two years after stopping the dapsone. The leukocytoclastic vasculitis was thought to have developed independently of the rheumatoid arthritis. She had noticed sicca symptoms two years before the appearance of EED, but she did not satisfy the diagnostic criteria for Sjögren's syndrome.

A 71-year-old Japanese man presented with asymptomatic, firm, brown-red papules on the dorsum of his left hand and back. A biopsy specimen revealed granulomatous infiltration consisting of multinucleated giant cells and histiocytes in the upper dermis. Elastic fibers were absent in the upper dermis, having been phagocytosed by giant cells. These papular elastolytic giant cell granuloma lesions regressed very well with narrow-band ul traviolet B irradiation, with only residual brown pigmentation left after treatment.

A rare case of papular mucinosis on the back of a 78-year old man is described. The patient developed approximately 20 discrete papules on the upper back. His serum glucose concentration was borderline elevated, but no other systemic symptoms or signs were apparent. A biopsy revealed mucin deposits only in the upper reticular dermis. The papules were distinctly different from lichen myxedematosus in clinical and histochemical appearance. The present case may represent very early-stage lichen myxedematosus complicated by borderline diabetes mellitus.

Two patients with disseminated superficial porokeratosis (DSP) with amyloid deposition are reported. The skin lesions were distributed over both sun-exposed areas and sun-protected areas. No exacerbation by sun exposure was noted. Abundant amyloid substances were deposited at the papillary dermis, not only beneath the cornoid lamellae but also within the annular margin. The skin lesions and amyloid deposition regressed with topical application of dimethyl sulfoxide in one patient, suggesting that DSP is one of the clinical phenotypes of primary localized cutaneous amyloidosis. Another possibility is that amyloid substances are produced by poorly differentiated keratinocytes in DSP.

The value of chemoradiation therapy (CRT) followed by surgery is unknown in Japan.Thirty Patients with TNM cStage II - III squamous cell carcinoma (SCC) of the esophagus were divided into CRT (40 Gy) followed by surgery( arm A) and definitive CRT( 60 Gy()arm B). The correlations between several clinicopathological factors and survival time were examined.The effective rate (CR+PR) of CRT was 75% in arm A versus 88.9% in arm B (p= 0.32). There was no significant difference about the median survival time (arm A: 17. 4 months, arm B: 12. 6 months, p= 0.18). The two-year survival rate was 40 . 4% in arm A versus 41 . 6% in arm B (p=0.35).Our retrospective study showed no significant difference in prognosis between CRT followed by surgery and definitive CRT. Definitive CRT might be a choice of therapy for curative esophageal carcinoma.

We reviewed the patients with neoadjuvant chemoradiotherapy (CRT) with S-1 to evaluate the feasibility and effectiveness for locally advanced lower rectal cancer. The CRT regimen consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy), five days a week. A treatment of oral S-1 (80 mg/m2 per day) on days 1-14 and 22-35 was given during radiotherapy. Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study was 60% (all were grade 2), and no patients had lateral lymph node metastases. Grade 1 or 2 adverse effects occurred in all patients during CRT, but the CRT was achieved in all patients. We found two patients had surgical complications with wound infection and one patient with anastomotic leakage. All complications were improved by conservative treatment. The neoadjuvant CRT was feasible and effective treatment for all patients with locally advanced rectal cancer. We have started a phase II study of the neoadjuvant CRT.

The patient was an 80-year-old woman who was diagnosed with locally advanced low rectal cancer. It was unresectable and we performed chemoradiotherapy combined with S-1 (S-1 80 mg/m2, RT 1.8 Gy × 25, total 45 Gy). An effective reduction of primary region resulted in curative resection (super low anterior resection, D3 lymph node dissection, covering ileostomy) with preserving the anal sphincter. Histopathologically, therapeutic efficacy was Grade 2. Preoperative chemoradiation has been a standard therapy in Western countries and would control local recurrence. This case indicated that CRT could improve a rate of curative resection in patients with locally advanced rectal carcinomas.

Epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3, and increased levels of cytokines and growth factors that promote Stat3 activation have been found within psoriatic lesions. K5.Stat3C transgenic mice, in which keratinocytes express a constitutively active Stat3, develop psoriasis-like skin lesions. In this study, we examined whether STA-21, a small Stat3 inhibitor, could be useful in ameliorating the skin lesions not only in the model mouse but also in human psoriasis. Treatment with STA-21 markedly inhibited the cytokine-dependent nuclear translocation of Stat3 in normal human keratinocytes in vitro. Keratinocyte proliferation was inhibited by STA-21 in a dose-dependent manner through downregulation of c-Myc and cyclin D1, whereas involucrin, transglutaminase 1, and keratin 10 levels were upregulated. Topical application of STA-21 abolished the generation of skin lesions in K5.Stat3C mice. Finally, we treated psoriasis patients with STA-21-containing ointment in a nonrandomized study. Psoriatic lesions in six of the eight patients showed improvement after topical STA-21 treatment for 2 weeks. Therefore, we conclude that targeting Stat3 may lead to a therapy for psoriasis.

We developed a new radiosensitization treatment using a hydrogen peroxide solution (Oxydol)-soaked gauze named KORTUC I (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas) for superficially exposed and unresectable neoplasms, such as malignant melanoma and malignant fibrous histiocytoma (MFH), based on our experimental results which demonstrated hydrogen peroxide as a strong radiosensitizer for the highly radioresistant osteosarcoma cell line, HS-Os-1. Five patients entered our clinical trial, one of whom had unresectable malignant melanoma; one, unresectable MFH; one, unresectable extramammary Paget's disease; one, locally advanced breast cancer and one with locally recurrent skin cancer. These patients were treated with radiation therapy using a high-energy electron beam from a linear accelerator. The total dose was 48 Gy, and each fraction size was 4 Gy. Radiation therapy for these patients was performed three times per week. Each time the radiation therapy was carried out, the superficially exposed tumors of these patients were covered with hydrogen peroxide solution (Oxydol)-soaked gauze, and the lesion was gently massaged for several minutes so as to allow the hydrogen peroxide solution to soak deeply into the tumor. In the treatment results, two of these five patients showed a clinically complete response (cCR) two to three months following the end of the KORTUC I radiosensitization treatment. The other three patients showed a clinically partial response (cCR) showing a decrement of more than half of the pretreatment volume. KORTUC I was completed without any severe complications, excluding mild radiation-induced dermatitis/mucositis (Grade I). In conclusion, this newly developed radiosensitization treatment using hydrogen peroxide solution (Oxydol)-soaked gauze for superficially exposed unresectable/radioresistant neoplasms appears to be an effective and valuable method of radiosensitization in terms of the blockade of anti-oxidative enzymes such as peroxidases, resulting in local oxygen production. Moreover, the KORTUC I radiosensitization treatment is relatively inexpensive and the method can therefore be utilized worldwide for many patients suffering from superficially exposed and locally advanced radioresistant neoplasms such as malignant melanoma, malignant fibrous histiocytoma (MFH) and various types of sarcomas.

Herpetiform vesicles and erythema with erosion developed on the trunk of a 48-year-old Japanese man. Acantholysis was observed in the spinous layer of the lesional epidermis and direct immunofluorescence revealed cell surface deposition of immunoglobulin IgG and C3. Indirect immunofluorescence could not detect circulating anti-cell surface antibodies. Immunoblot analysis detected neither anti-desmoglein (Dsg)1 antibody nor anti-Dsg3 antibody. Enzyme-linked immunosorbent assay could detect IgG and IgA anti-Dsg 1 antibodies and IgA anti-Dsg3 antibody, in addition to a gray zone titer of IgG anti-Dsg3 antibody. Intraepidermal neutrophilic infiltration with neutrophilic microabscesses and intense dyskeratotic cells were histopathologically characteristic in this case. Skin lesions improved within 1 month and remission has continued for 9 years under oral administration of dapsone.

A 5-month-old boy was noted to have brown macules with palpable infiltration on the head, trunk, and extremities a few weeks after birth, with recurrent episodes of generalized flushing and blistering in some of the macules. These lesions developed into yellowish plaques after 1 year of topical treatment with clobetasol propionate. Serum lipid levels were within normal limits. The appearance of the yellowish lesions was similar to that of the xanthelasmoid type of cutaneous mastocytosis. The brown macules showed infiltration of a large number of mast cells and a small number of scattered foam cells, whereas in the yellowish plaques, the number of foam cells was greatly increased. The yellowish plaques regressed spontaneously within a year after cessation of topical corticosteroid treatment. Immunohistochemical analysis found that the foam cells were stained with monocyte/macrophage markers including HAM56, and with SRA-C6, a monoclonal antibody to macrophage scavenger receptor class A (CD204). Therefore, the yellowish plaques were considered to be plane xanthoma associated with cutaneous mastocytoma.

Background: The migration of circulating monocytes into the dermis is considered to be essential for both the initiation and the progression of xanthoma. The contribution of vascular endothelial cells to the migration process is unclear. Methods: Twenty cases of xanthelasma and six cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results: Xanthoma lesions contained up to 25-fold more von Willebrand factor-stained endothelial cells than normal skin. The prevalence of E-selectin-positive endothelial cells increased by up to threefold more in xanthoma lesions than in normal skin. In contrast, the prevalence of intercellular cell adhesion molecule-1 (ICAM-1) decreased up to 3.5-fold more in xanthoma lesions than in normal skin. In xanthoma lesions, almost all ICAM-1-positive endothelial cells co-expressed with E-selectin but many endothelial cells, which only expressed E-selectin, were also found in the lesions and the ratio of macrophages to endothelial cells was higher (10:1) than that in normal skin (5:1). Conclusions: Endothelial cells proliferate and express E-selectin rather than ICAM-1 under a microenvironment in which macrophages predominate rather than endothelial cells, thereby promoting macrophage migration into xanthoma lesions.

Pseudoxanthoma elasticum is an inherited systemic disorder of connective tissue characterized by fragmentation of elastic fibers and calcification in cutaneous, ocular, and cardiovascular systems. Mutation in the ATP-binding cassette subfamily C member 6 gene has recently been found in people with pseudoxanthoma elasticum (1). However, the precise mechanisms of elastic fiber fragmentation and calcification remain obscure. Recently, it has been reported that mild chronic oxidative stress affects pseudoxanthoma elasticum fibroblasts (2). This suggests that reactive oxygen scavengers might improve this disorder.

Background : Oxidation of low density lipoprotein (LDL) has been implicated in infiltration of foam cells derived from circulating monocytes. Monocyte adhesion to endothelial cells and migration into dermis are essential steps for infiltration of foam cells. Objective : We investigated the role of adhesion molecules contributing to the process of monocyte adhesion to human dermal microvascular endothelial cells (HDMEC). Special attention was paid to the signal transduction for adhesion molecule expression induced by two distinct types of oxidized LDL. Methods : HDMEC were incubated with xanthoma tissue-modified LDL (x-LDL), a model of extravasated LDL oxidized in xanthoma lesions, or Cu 2+ -treated LDL (Cu-LDL), a model of oxidized LDL. Adhesion of U937 cells, a human monocytic leukemia cell line, to HDMEC and expression of endothelial cell adhesion molecules on HDMEC were examined. Signal transduction pathways for the adhesion molecule expression were evaluated by employing specific inhibitors. Results : x-LDL induced adhesion of U937 cells to HDMEC through vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by activating tyrosine kinase pathway. Cu-LDL up-regulated the adhesion through not only VCAM-1 and E-selectin but also intercellular cell adhesion molecule-1 (ICAM-1) by activating G i protein pathway. Conclusion : Extravasated and oxidized LDL in xanthoma lesions contributes to foam cell recruitment by activating tyrosine kinase pathway and inducing adhesion of monocytes to HDMEC through VCAM-1 and E-selectin. Cu-LDL, on the other hand, activates G i protein pathway and induces the adhesion through ICAM-1, VCAM-1 and E-selectin.

Implantation of epidermal fragments into the dermis has been pointed out as the cause of common epidermal cysts. However, some palmoplantar epidermoid cysts have been reported to be caused by human papillomavirus (HPV) infection or to be derived from eccrine ducts. A 65-year-old left-handed woman presented with extraordinary multiple epidermoid cysts on the palm and volar aspect of the fingers of her left hand. HPV infection was not detected by immunohistochemistry, in situ hybridization and polymerase chain reaction. Histological investigation revealed syringeal structures within the cyst wall and in the cyst cavity. Carcinoembryonic antigen was observed in these syringeal structures but was not specifically stained in the cyst wall cells by immunohistochemistry. The cytokeratin composition of the cyst wall cells was similar to that of the nonadnexal epidermis.

The estrogen receptor (ER) is composed of six major functional domains - the A/B domain as the activation function 1 domain, domain C as the DNA-binding domain, domain D as a hinge domain, and domain E/F as the ligand-dependent transcriptional domains. A novel protein (designated as SRB-RGS) that interacted with domains C and D of ER alpha (ER alpha C/D) repressed the transcriptional activity of ER alpha. In this study, we have examined whether ER alpha C/D releases transcriptional suppression of ER alpha by intrinsic SRB-RGS. The expression vector of ER alpha C/D was transfected to the human cancer cell, KPL-1, which expressed the intrinsic ER. Unexpectedly, transcriptional suppression of ER by ER alpha C/D was observed. COS-7 cells, which have no intrinsic ER, showed a similar suppression of ER alpha by co-transfection of ER alpha and ER alpha C/D. The DNA-binding and the estrogen-binding activities of ER alpha decreased on co-transfection of ER alpha C/D, suggesting a decrease in the receptor protein itself. It is likely that the degradation of ER by co-transfection caused the transcriptional suppression of the ER.

A 61-year-old man presented with purple-red papules and plaques. These lesions on the nape and dorsal aspects of both hands displayed the histological findings characteristic of lichen planus. Riehl's melanosis, which is synonymous with pigmented contact dermatitis, was present on the forehead and bald scalp. Riehl's melanosis typically appears on the face and is induced by cosmetics. Causative factors in this case, however, remained undefined. The coexistence of lichen planus and Riehl's melanosis at separate sites in a single patient suggests that the two diseases represent manifestations of specific immune responses characteristic of lichenoid tissue reaction and situate in the same spectrum. The differences in the skin manifestations of lichen planus and Riehl's melanosis might depend on the severity of immune responses against intrinsic or extrinsic antigens. In addition, the skin manifestations of lichenoid tissue reaction might depend on the disposition of the lesion sites.

A 42-year-old baker had hyperkeratotic lesions on reticular erythema of his palms and volar digits. Attachment between the epidermis and the dermis was loose at the hyperkeratotic sites, but no blisters had formed. After he stopped work for 2 months, the skin lesions disappeared, leaving a slight scar. Immunofluorescence studies showed a normal distribution of type VII collagen and laminin, but there was almost no fluorescence for type IV collagen in the basement membrane zone. Disappearance of cytoplasmic organelles and aggregated tonofibrils was evident under electron microscopy in the basal cells which appeared shrunken under light microscopy. The structures of lamina lucida, basal lamina and anchoring fibrils were disarranged. The loose dermo-epidermal attachment is probably due in part to this disorganized basement membrane structure lacking type IV collagen, which may have been digested by heat-activated matrix metalloproteinases. In addition, his work-related chronic heat exposure might have caused hyperproliferation of keratinocytes.

A 35-year-old woman with left frontoparietal glioblastoma was subtotally resected twice and 1 year later demonstrated extracranial metastasis. Magnetic resonance imaging (MRI) demonstrated metastasis to the first thoracic vertebral body with epidural and paravertebral extension. Bone scintigrams of the spine appeared normal. The mechanisms and radiological findings of the extracranial metastasis of an astrocytic glioma are reviewed.

Phyllodes tumor is an uncommon fibroepithelial breast tumor. The authors describe a patient with a benign phyllodes tumor of the breast who underwent Tc-99m MDP scintimammography. Definitely increased activity at the site corresponding to the tumor was observed on images obtained soon after the injection of Tc-99m MDP. The mass was excised, and pathologic analysis showed it to be a benign phyllodes tumor. The case reported indicates that benign phyllodes tumor is a possible cause of false-positive findings on scintimammography with Tc-99m MDP.

Angiosarcoma is a rare form of primary hepatic neoplasm. Blood pool scans using Tc-99m red blood cells or Tc-99m human serum albumin (HSA) are known to be useful in the diagnosis of vascular tumors, including angiosarcoma. The authors report a large exophytic hepatic angiosarcoma in which Tc-99m HSA imaging failed to demonstrate increased radioactivity even on the 90-minute image.

The mouse macrophage-like cell line, J774.1, spontaneously released differentiation-inducing factor(s). When these cells were treated with a protein-bound polysaccharide, PSK, significantly higher amounts of differentiation-inducing activity were accumulated in the culture supernatant. PSK directly stimulated human myelogenous leukemic cell differentiation induced by J774.1 conditioned medium or by tumor necrosis factor. Among four subfractions of PSK, only the highest molecular weight fraction (MW greater than 200 kD) exerted such a stimulating effect.

3-Hydroxy-17β-(p-nitrophenyldithio)-1, 3, 5(10)-estratriene (Reagent A), an affinity labeling reagent for estrogen receptor, was prepared by iodine oxidation of an alkaline mixture of 3-hydroxy-1, 3, 5(10)-estratriene-17β-thiol and p-nitrothiophenol in 50% ethanol, and was isolated in a pure state. The structure was confirmed by the physical as well as spectral properties. The biological activity of the compound was tested by the measurement of the effects of 3H-thymidine incorporation into deoxyribonucleic acid (DNA) and on 14C-uridine incorporation into ribonucleic acid (RNA) in a human breast cancer cell line, MCF-7. There were increases of about 2-fold in thymidine incorporation and of about 1.1- to 2-fold in uridine incorporation in cells in-cubated in 10-7M Reagent A compared with the control.

Intercellular adhesion molecule-1 (ICAM-1) is strongly expressed by human epidermal keratinocytes during the course of inflammatory skin diseases. To test the possibility that reactive oxygen species produced in the skin during an inflammatory response affect ICAM-1 expression, cultured human epidermal keratinocytes were treated with H2O2 at concentrations that did not damage the cells, and cell-surface ICAM-1 expression was analyzed. Expression of ICAM-1 was induced on keratinocytes by treatment with 300 microM H2O2 for 1 h. The antioxidant N-acetyl-L-cysteine strongly inhibited H2O2-induced ICAM-1 expression, whereas the antioxidants pyrrolidine dithiocarbamate and alpha-tocopherol were less inhibitory. N-acetyl-L-cysteine also suppressed keratinocyte surface expression of ICAM-1 induced by the cytokines interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha), whereas pyrrolidine dithiocarbamate and alpha-tocopherol suppressed IFN-gamma-induced surface expression but not TNF-alpha-induced expression. We found that N-acetyl-L-cysteine treatment reduced ICAM-1 mRNA levels when keratinocytes were stimulated with either IFN-gamma or TNF-alpha; however, pyrrolidine dithiocarbamate and alpha-tocopherol had no effect on either IFN-gamma- or TNF-alpha-induced ICAM-1 mRNA levels. Our results indicate that reactive oxygen species may be involved in the skin inflammatory process by increasing epidermal ICAM-1 expression and that some antioxidants may be effective in suppressing the epidermal ICAM-1 expression induced by reactive oxygen species and cytokines in inflammatory skin diseases.

The effects of estrogen and antiestrogen on chromatin in the human breast cancer line, MCF-7 were studied in cells grown in media containing 10-8M estradiol or 10-6M tamoxifen for 1, 3 and 8 d. The nuclear binding sites of the estradiol-and tamoxifen-receptor complexes were determined using intact cells. The nuclear content of the estradiol-receptor complex reached a plateau level on day 1. Nuclear tamoxifen binding sites were still increasing on day 3. The binding capacity of the chromatin for the estradiol-receptor complex was determined in a cell-free system. It was increased by incubation for 1-3d and then decreased by incubation for 8 d. In addition, the sodium dodecyl sulfate-gel electrophoretic patterns of chromosomal proteins from MCF-7 cells grown in media containing 10-8M estradiol 10-6M tamoxifen, or vehicle alone for 8 d were compared. The patterns were quite similar, but differences in some bands could be detected.

The extraction of [3H]estradiol- and [3H]tamoxifen-receptor complex in the nuclei from MCF-7 cells with the nonionic detergent Nonidet P-40 has been studied. We found that there is a striking difference in the extractability of estradiol- and tamoxifen-receptor complex from nuclei with 0.5% Nonidet P-40. The nuclear bound estradiol-receptor complex is scarcely extractable with Nonidet P-40. In contrast, almost all of the nuclear bound tamoxifen-receptor complex is extractable. The nuclear [3H]tamoxifen-receptor complex extracted in the presence of Nonidet P-40 sediments in two peaks at 7 S and 5 S. The latter sedimentation rate is the same with that of the nuclear [3H]tamoxifen-receptor complex extracted with 0.4 M KC1. The nuclear [3H]estradiol-receptor complex extracted with 0.4 M KC1 sediments at 4 S. The results suggest that interaction of tamoxifen-receptor complex with chromatin is different from that of estradiol-receptor complex.