Fibronectin inhibits endocytosis of calcium oxalate crystals by renal tubular cells

BACKGROUND: Fibronectin (FN; 230 kDa) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. We recently reported that FN has a protective effect against injury of renal tubular cells by exposure to oxalate and calcium oxalate (CaOX) crystals and inhibits the adhesion of CaOX crystals to renal tubular cells. In the study presented here, we investigated whether FN has inhibitory effect on crystal endocytosis by renal tubular cells. METHODS: The inhibitory effect of FN on endocytosis of CaOX crystals by MDCK cells was examined by using a radioactivity uptake assay. Also, crystal endocytosis by cells was morphologically assessed by means of transmission electron microscopy (TEM). RESULTS: FN had inhibitory effects on CaOX crystal endocytosis by MDCK cells. The morphological TEM study showed that few crystals were taken into cells when FN was added compared to the number of crystals when FN was not added. CONCLUSION: We found that FN had the inhibitory effects on the interaction between crystals and renal tubular cells, including the adhesion or endocytosis of crystals by cells.     

Phase II Study of Mitoxantrone in Patients With Non-Small Cell Lung Cancer

A phase II study of mitoxantrone was performed in 24 patientswith non-small cell lung cancer (NSCLC). Mitoxantrone was administeredby intravenous drip infusion of 12 mg/m² every three weeks.There were no responders among the 21 evaluable patients includingfive patients without prior therapy. The major hematologicaltoxic effect was leukocytopenia. Thrombocytopenia and decreasein hemoglobin were slight. A change in the electrocardiogramwas observed in one patient and one patient experienced cardiogenicshock. Mitoxantrone is not acceptable for the treatment of NSCLC becauseof its low antitumor activity, and careful observation is neededfor administration of this agent to patients with pre-existingrisk factors, such as prior anthracycline exposure, mediastinalradiation or underlying cardiovascular disease.     

Prevalence of and risk factors for nocturia: Analysis of a health screening program

BACKGROUND: We examined the prevalence of and risk factors for nocturia in Kurashiki city and the surrounding area, a rural area in Japan. MATERIALS AND METHODS: We collected data on 6517 individuals (4568 men and 1949 women) who participated in a multiphasic health screening. We analyzed the relationships between nocturia assessed by a questionnaire (voiding twice or more during night) and other variables including age, hypertension, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus (DM), chronic renal failure, benign prostatic hyperplasia (BPH), smoking habit and alcohol intake. RESULTS: Overall, 1856 individuals (28.5%) answered that they arose to urinate at least twice during the night. This rate increased with age from 16.5% in individuals younger than 50 to 60.0% in those older than 69. Logistic regression analysis revealed that cohorts of subjects 50-59, 60-69, and 70 years old or over had, respectively, 1.75, 3.35, and 6.21 times the prevalence of nocturia of the 49 years or younger cohort. Hypertension (odds ratio [OR] 1.64) and DM (OR 1.70) were other independent positive risk factors for nocturia. On the other hand, current smokers who smoked 20 or more cigarettes per day were less likely to have nocturia than non-smokers (OR 0.72). In male individuals, BPH was another independent positive risk factor (OR 1.35). Gender was not associated with nocturia. CONCLUSIONS: Although population bias is an important limitation to this study, nocturia is associated with various factors suggesting that multiple approaches are needed to the treatment of patients with nocturia.     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Augmented Lung Adenocarcinoma Cytotoxicity by the Combination of a Genetically Modified Anti-Lewis Y Antibody and Antibodies to Complement Regulatory Proteins

Nine vervet monkeys ( Cercopithecus aethiops ) were infected intradermally with 8 × 10⁷ virulent L. donovani promastigotes. Four animals developed clinical visceral leishmaniasis and died over a period of 18 months. The remaining five animals have remained asymptomatic for a period of 3 years now. Attempts to isolate parasites from spleen and liver through biopsies were fruitless. Immunological respotises of these subclinically infected animals were examined. Enzyme-linked itnmunosorbent assay ( ELISA ) and western blot analyses demonstrated Leishmania specific antibodies in these animals, but the antibody titres were low. When proliferation of peripheral blood monocytes ( PBMC ) to Con-cunavalin A (Con A) of these animals was compared with control 'disease free animals' there were no significant differences iti response. However L. donovani antigen (fixed promastigotes) specific proliferation was demonstrated in the five subclinically infected animals. High and varying levels of interferon gamma (IFN-γ) were secreted in PBMC cultures from the five vervet monkeys when stimulated with either Con A or L. donovani antigens. In control animals, IFN-γ was only detected wheti PBMC were stimulated with Con A. Marked delayed-type hypersensitivity ( DTH ) responses were demonstrated in the five subclinically infected animals 48 h after injection with formalin fixed promastgotes.
It was concluded that the visceral Leishmania disease spectrum due to L. donovani observed in humans could be induced in vervet monkeys and that L. donovani asymptomatic/cryptic infected animals have competent humoral and cellular responses to homologous parasites.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

Benign Tumors and Tumor-Like Lesions (Excluding Adenomas) of the Lung: Radiological and Clinicopathological Analysis of 48 Cases

Forty-eight cases of surgically resected benign tumors and tumor-likelesions of the lung were analyzed, with the following results:1) Hamartoma and sclerosing hemangioma have well defined borders,compressing bronchi and blood vessels, and are loosely boundto the surrounding lung parenchyma. 2) Hamartomas, in 90% ofthe cases, showed "nodularity" on film tomograms. Histologically,nodularity at the edge was produced by lobules of cartilage.3) Fifty-three percent of the patients with sclerosing hemangiomawere middle-aged females and asymptomatic. Only two patientscomplained of hemosputum. Routine roentgenograms showed a roundshadow with homogeneous density. Cut surfaces were solid withvarious degrees of hasemorrhage. 4) Roentgenograms of benignmesothelioma showed large tumors more than 4 cm in diameter,in which extrapleural signs could be observed. 5) "Calcification"was seen on the roentgenograms of seven out of 27 hamartomasand one out of 15 sclerosing hemangiomas. Pleural retractioncould not be seen in our series. Xerotomography was superiorto film tomography in showing calcification. 6) One of the sclerosinghemangiomas was double, and the other 47 benign tumors and tumor-likelesions were solitary; the lesions were peripheral in 45 casesand central in three. All of the patients were free of localrecurrence and distant metastasis.     

Atrial Electrograms and Activation Sequences in the Transition Between Atrial Fibrillation and Atrial Flutter

Transition Between Atrial Fibrillation and Flutter. Introduction: The eletrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFI), which was right atrial (RA) arrhythmia, and sought to investigate intra-atrial electrograms and activation sequences in the transition between AF and AFL.
Methods and Results: Intra-atrial electrograms and activation sequences in the R.A free wall and the septum were evaluated in the transition between AF and AFL in seven patients without organic heart disease (all men; mean age 57 ± 11 years). In five episodes of the conversion of AFL into AF, the AFL cycle length was shortened (from 211 ± 6 msec in stable AFL to 190 ± 15 msec before the conversion, P, 0.001). Interruption of the AFL wavefront and an abrupt activation sequential change induced by a premature atrial impulse resulted in fractionation and disorganization of the septal electrograms. During sustained AF, septal electrograms were persistently fractionated with disorganized activation sequences. However, the RA free-wall electrograms were organized, and the activation sequence was predominantly craniocaudal rather than caudocranial throughout AF. In 12 episodes of the conversion of AF into AFL, the AF cycle length measured in the RA free wall increased (from 165 ± 26 msec at the onset of AF to 180 ± 24 msec before the conversion, P, 0.001). AFL resumed when fractionated septal electrograms were separated and organized to the caudocranial direction, despite the RA free-wall electrograms remaining discrete and sharp with an isoelectric line.
Conclusion: Changes of the electrogram and activation sequence in the atrial septum played an important role in the transition between AF and AFL.