The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin's tight junction barrier.

BACKGROUND: S100A7/psoriasin is a member of the S100 protein family and is encoded in the epidermal differentiation complex, which contains genes for markers of epidermal differentiation. S100A7/psoriasin is overexpressed in hyperproliferative skin diseases, where it is believed not only to exhibit antimicrobial functions, but also to induce immunomodulatory activities, including chemotaxis and cytokine/chemokine production. OBJECTIVES: To evaluate the effect of S100A7/psoriasin on keratinocyte differentiation and regulation of the tight junction (TJ) barrier. METHODS: Expression of differentiation markers and TJ proteins in human keratinocytes was determined by real-time polymerase chain reaction and Western blot. The changes in TJ barrier function were assessed by transepithelial electrical resistance and paracellular permeability assays. Glycogen synthase kinase-3 (GSK-3) and mitogen-activated protein kinase (MAPK) activation was analysed by Western blot, whereas ß-catenin and E-cadherin activation was evaluated by Western blot and immunofluorescence. RESULTS: S100A7/psoriasin enhanced the expression of several differentiation markers and selectively increased the expression of TJ proteins (e.g. claudins and occludin), which are known to strengthen the TJ barrier. Furthermore, S100A7/psoriasin increased ß-catenin and E-cadherin accumulation at cell-cell contact, and enhanced transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers. The data suggest that S100A7/psoriasin-mediated regulation of the TJ barrier was via both the GSK-3 and MAPK pathways, as evidenced by the inhibitory effects of inhibitors for GSK-3 and MAPKs. CONCLUSIONS: Our finding that S100A7/psoriasin regulates differentiation and strengthens TJ barrier function provides novel evidence that, in addition to antimicrobial and immunoregulatory activities, S100A7/psoriasin is involved in skin innate immunity.

[Radiological assessment of the structural relationship between the trachea and the innominate artery in physically disabled and scoliotic children].

Studies were made on the physically disabled and scoliotic children who underwent tracheostomy. The purpose was to clarify factors that might lead to the tracheo-innominate artery fistula, by use of three-dimensional helical CT (3 DCT). In a case of right scoliosis, the tracheo-innominate artery fistula may be caused by the left-ward displacement of the trachea from the vertebra, having the innominate artery ride over the trachea and compressing it. In a case of the physically disabled and scoliotic children, there may be more compression on the trachea by the innominate artery along with the worsening scoliosis. Therefore, we consider it necessary to examine the structural relationship between the trachea, the vertebra, and the innominate artery periodically by 3 DCT.

Propiverine-induced Parkinsonism: a case report and a pharmacokinetic/pharmacodynamic study in mice.

PURPOSE: We present a case report of propiverine-induced Parkinsonism. We previously reported the induction of catalepsy by amiodarone, aprindine and procaine, which possess a diethylaminomethyl moiety and demonstrated selective blockade of dopamine D2 receptors by these drugs in mice. We hypothesized that drugs possessing a diethylaminomethyl structure may generally induce Parkinsonism and/or catalepsy. METHODS: Thus, we performed a study to examine whether oxybutynin, pentoxyverine and etafenone, as well as propiverine, induce catalepsy in mice. RESULTS: The intensity of drug-induced catalepsy was in the order: haloperidol > etafenone > pentoxyverine > propiverine > oxybutynin. In vivo occupancy of dopamine D1, D2 and mACh receptors in the striatum was also examined. The in vitro binding affinities to the D1, D2 and mACh receptors in the striatum synaptic membrane were within the ranges of 2.4-140 microM, 380-4,200 nM, and 1.2-2,800 nM, respectively. CONCLUSIONS: These results support the idea that any drug possessing a diethylaminomethyl moiety may contribute to the induction of catalepsy, possibly by occupying dopamine receptors.

Sudden death in chronic dialysis patients.

METHODS: Causes of sudden death were investigated in 113 chronic dialysis patients who died during the 10-year period from July 1979 to January 1989; postmortem examination was performed on 93 of the cases (autopsy rate; 82.3%). Sudden death was regarded as death 24 h after the onset of acute illness in patients without any restriction in their daily activities. There were 35 sudden death cases out of the 93 autopsied chronic dialysis patients. We analysed the causes of sudden death for all chronic dialysis patients and for those who died suddenly. RESULTS: The mean age of the 93 cases was 61.4 +/- 10.5 years (+/-SD). Stroke was the most frequent cause of death (24 cases, 25.8%) in the 93 autopsied cases. This was followed by cardiac disease in 18 (19.4%), infectious disease in 16 (17.2%), malignancy in 14 (15.1%), and dissecting aortic aneurysm in 5 (5.4%). The mean age of the 35 sudden death cases was 60.9 +/- 10.9 years. Of the 35 sudden death cases in chronic dialysis patients, dissecting aortic aneurysm was the most common cause of sudden death (5 cases, 14.3%), followed by cerebral haemorrhage in three (8.6%), acute subdural haematoma in three (8.6%), acute myocardial infarction in two (5.7%), cerebral infarction in two (5.7%), and subarachnoidal haemorrhage in one (2.9%). CONCLUSIONS: Dissecting aortic aneurysm, leading frequently to stroke as a cause of sudden death in chronic dialysis patients, at least in Japan, should be carefully differentiated from other cardiac diseases in chronic dialysis patients, such as severe atherosclerosis.

Combined therapy with arbekacin and fosfomycin for methicillin-resistant Staphylococcus aureus infections.

We examined the clinical efficacy of a combination of arbekacin and fosfomycin in the treatment of various methicillin-resistant Staphylococcus aureus (MRSA) infections. The combination of arbekacin plus fosfomycin displayed 65.4% (17/26) clinical efficacy and 65.4% (17/26) bacteriological efficacy. This combination thus appeared to be an effective regimen for the treatment of MRSA infections. However, its bacteriological efficacy against concomitant Pseudomonas aeruginosa strains was only 16.7% (1/6). In addition, in 4 episodes of superinfection involving P. aeruginosa strains developed during the combination therapy.

Primary hyperoxaluria type I due to a point mutation of T to C in the coding region of the serine:pyruvate aminotransferase gene.

cDNA clones for serine:pyruvate aminotransferase (SPT, alternative name: alanine:glyoxylate aminotransferase) were obtained from a cDNA library constructed from the liver of a primary hyperoxaluria type I (PH1) case in which the SPT activity was approximately one-hundredth that in control liver. Six clones were isolated from 100,000 transformants and all of them contained an approximately 1.5 kbp insert which included the whole coding region for human SPT. Nucleotide sequence analysis revealed a point mutation of T to C at position 634 (relative to the 5'-end of the cDNA) encoding a Ser to Pro substitution at residue 205. The T to C conversion created a new SmaI site, which enabled us to demonstrate that the point mutation had occurred in the patient's SPT gene. SmaI digestion of genomic DNA may be useful for the diagnostic gene analysis of this type of PH1.

[Clinico-pathological studies on Is, Ip polyps and flat elevations in the large intestine].

We histologically compared 3 types of adenoma and cancer of the large intestine using 620 adenoma specimens (509 Is type lesions, 83 Ip type lesions, and 28 flat type lesions) and 113 specimens of early stage cancer (51 Is type lesions, 39 Ip type lesions, and 23 flat type lesions) obtained during the past 5-year period at our department. More than 90% of the Is and Ip type polyps were adenoma or carcinoma in adenoma while 25.5% of the flat elevations were m or sm carcinoma. Flat elevations even less than 10 mm in diameter were frequently carcinomas (26.3%) compared with the other types (both Is and Ip types, 6.7%), and all of those 10 mm or more in size were carcinomas. The distribution of the flat type early cancers in the large intestine was similar to that of advanced cancer with high percentages of carcinoma at each site compared with the other types. These results suggest that the carcinogenesis and progression of flat type early stage cancer differ from those of the other types.

[Prognosis of intra-arterial chemo-embolization in metastatic liver cancer].

We treated 63 patients (pts) suffering from metastatic liver cancer with intra-arterial infusion chemotherapy, and analysed 44 of their for survival since the first treatment with regard to the primary foci of cancer and the method of intra-arterial therapy. Via the superficial femoral artery, we performed superselective hepatic catheterization by Seldinger's method. Three types of intraarterial therapy were used: Gelfoam embolization with mitomycin-C (MMC) in 12 pts (GS-TAE), capillary chemo-embolization with MMC-Lipiodol emulsion in 28 pts (LP-TAI) and "one-shot" slow infusion of MMC or cisplatinum in 4 pts. Fifty-percent survival was 189 days in pts with metastases from colo-rectal cancer (n = 20), 109 days from gastric cancer (n = 9), 100 days from pancreatobiliary cancer (n = 5) and 240 days from breast cancer (n = 7). More than one-year survival was obtained in 13 out of the 40 pts (32.5%). Survival of 12 pts, treated with GS-TAE regimen, was not significantly superior to that of 28 pts with LP-TAI regimen. Hence, we conclude that LP-TAI is the treatment of choice in chemo-embolization for unresectable liver metastases, because it causes less damage to the hepatic arterial beds, and facilitates repeat intraarterial therapy in these pts.

[Preoperative chemoembolization of iopamiron-solved adriamycin and lipiodol on hepatocellular carcinoma--clinicopathological study of ten surgical cases].

Preoperative chemoembolization was performed in 10 patients with hepatocellular carcinoma. The therapeutic regimen included Adriamycin (ADM) solved in nonionic contrast media, Iopamiron and Lipiodol (LP). Two to four ml of the solution, containing 20-40 mg of ADM, was mixed with 5-10 ml of LP by "pumping" method. This emulsion was infused superselectively into the hepatic artery by the balloon-occluded method. The regimen contained no permanent embolic material (e.g., Gelfoam or Ivaron). Dense deposition of LP in the tumor was seen on the CT scan 3-4 weeks after TAI. Surgical specimens, resected 3-12 weeks after TAI, revealed total necrosis of the tumor in 4 cases, subtotal necrosis (more than 80% on the cut surface) in 3 cases, and partial necrosis (less than 80%) in 3 cases. Tumor invasion in the fibrous capsules was necrosed in 4/7 of the cases. Tumor thrombi in the portal vein were also necrosed in 2/4. Our new method is more effective than the previous ones of LP and ADM without Iopamiron, and is equally effective as the regimen using LP, anticancer drugs, and permanent embolic materials.

[A case of colonic carcinoma associated with intestinal tuberculosis, and an analysis of 26 cases reported in Japan].

A case of tuberculosis and adenocarcinoma co-existing in the ileocecal region in a 61-yr-old woman is described. The Japanese literature is reviewed and several points discussed regarding the epidemiological and morphological features in a colon carcinoma associated with tuberculosis. (1) Females predominate by a ratio of 17:9 in such cases. (2) The tumor has been found in the right side of the colon in 17 out of 26 cases. (3) The most characteristic histological finding is that of the cancer, which shows a well differentiated adenocarcinoma with a tendency to produce a mucin. These unique findings are consistent with those in our case. It is of interest that these unique findings may support the possibility that the cancer originated from a tuberculous lesion.

Gastric leiomyoblastoma: report of a case.

The case of a 38-year-old man with an exogastric leiomyoblastoma is reported. CT and ultrasound examinations revealed a large mass in the left hypochondrium that had both solid and cystic components. These findings mimicked those of cystadenoma of the pancreas. Because of intraperitoneal hemorrhage in the preoperative course, emergency laparotomy was performed. A large tumor was found to arise from the greater curvature of the stomach. The diagnosis was confirmed histologically.

An experimental study on the origin of foam cells in glomerulonephritis.

Masugi nephritis induced in cholesterol-fed rabbits is characterized by accumulation of foam cells in glomeruli which vary in number almost in parallel with the natural course of the disease. From electron microscopic appearances these foam cells are apparently derived from migrant blood monocytes and mesangial cells, but not from endothelial cells. Location of monocytic foam cells is extremely variable, though most often observed in the subendothelial space. In addition, monocytes undergo transformation into multinucleated giant cells including Touton type's. Lipid deposits filling the cytoplasm of foam cells seem to be in two forms, free cytoplasmic droplets and membrane-bounded structures partly containing membranous debris or myelin figures. The latter accumulates preferentially in the cytocentrum and is considered to originate from lysosomes. It seems unlikely that glomerular lesions in Masugi nephritis are aggravated by foam cell accumulation.

Immunological analysis of plasminogen activators from cultured human cancer cells.

Immunological similarities or differences between urokinase and plasminogen activators from 9 lines of cultured human cancer cells with varying degrees of fibrinolytic activity were examined with antibodies against human urokinase. The antibodies completely inhibited the fibrinolytic activity of 4 lines of gastric cancer, 2 lines of lung cancer, 1 line of urinary bladder cancer and 1 line of renal cancer, indicating that the plasminogen activators from these cell lines were immunologically identical to urokinase. In 5 out of these cell lines, immunological identity was also confirmed by double diffusion analysis. The plasminogen activator from 1 line of lung cancer was found to be immunologically dissimilar to urokinase by a neutralization experiment and double diffusion analysis. These findings indicate that there are at least two immunologically distinguishable forms of plasminogen activators from human cancer cells.