The mechanism of action of tumor necrosis factor (TNF) on tumor vascularity--study using a transparent chamber

Effects of human recombinant TNF on the tumor blood vessels and on the thrombus formation were investigated in relation to its mode of antitumor action against Meth-A sarcoma transplanted in BALB/c mice. The extent of the blood vessel lesion was evaluated by using transparent chamber placed in the mouse skin. Bleeding, hyperemia and congestion were observed at 1-2h, 4-6h and 24h after TNF (1 X 10(4)U/mouse) administration, respectively. In contrast, no histological changes in the normal blood vessels were observed microscopically following TNF injection. Thrombus formation was evoked in the tumor vessels 4h after TNF injection. However, when thrombus formation was prevented by heparin, no difference was observed among antitumor action of TNF against Meth-A fibrosarcoma necrotic response and the rate of complete cure. These results suggest that the direct effects of TNF causing lesions in the tumor blood vessels plays an important role in its antitumor action.     

Benign schwannoma of the pancreas

Reported cases of intrapancreatic schwannomas have recently increased in the literature. However, none of these cases were diagnosed clearly as schwannoma preoperatively. We herein describe the clinicopathologic findings of a solitary benign schwannoma occurring in the head of the pancreas. Additionally, the differential diagnosis versus other cystic- and solid-appearing pancreatic masses is briefly discussed.     

Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established risk factors for cardiovascular disease. We analyzed the cardiovascular events in hyperlipidemic patients with or without DM who were administered open-labeled simvastatin in groups stratified by blood pressure level using data from the Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288) had significantly more cardiovascular events than those without DM (n=33,933). The incidence rates of total cardiovascular events in the Non-DM and DM groups were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The relative risk of total cardiovascular events in the DM vs. the Non-DM group was 1.68, and the relative risk was significantly higher in the DM than in the Non-DM group. The relative risks of total cardiovascular events were significantly higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP) was greater than or equal to 80 mmHg compared to that of Non-DM patients whose DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative risks of total cardiovascular events were higher in DM patients than in Non-DM patients. For patients with hypercholesterolemia and DM, blood pressure should be strictly controlled in order to prevent both coronary events and stroke. These results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg, respectively.     

Spatially and Temporally Regulated Modification of the Receptor-like Protein Tvrosine Phosphatase ζ/β isoforms with Keratan Sulphate in the Developing Chick Brain

Protein tyrosine phosphatase ζ (PTPζRPTPβ) is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. In addition to the transmembrane form (PTPζ-A), the extracellular splice variant (PTPζ-S) occurs as a major soluble chondroitin sulphate proteoglycan in the brain. We prepared antibodies which specifically recognize PTPζ-A and -S, and analysed the carbohydrate structures on the two PTPζ isoforms in the developing chick brain. lmmunoprecipitation experiments using these antibodies revealed that almost all of the keratan sulphate recognized by a monoclonal antibody (5D4) was exclusively bound to PTPζ-A and PTPζ-S. Addition of keratan sulphate to these proteoglycans markedly increased from embryonic day (E) 11, in contrast to the addition of Le^X and HNK-1 carbohydrates, which gradually increased during development in accordance with expression of the core proteins, suggesting that keratan sulphate modification plays some specific roles. Moreover, at the early embryonic stage keratan sulphate was observed only in several restricted regions, especially at boundary regions such as the roof plate of the tectum, the zona limitans intrathalamica in the diencephalon, and the mesencephalon-metencephalon boundary. At the mesencephalon-metencephalon boundary, keratan sulphate modification of PTPζ isoforms was specifically observed from E3 to E6 on a ring of cells encircling the neural tube and their radially oriented processes, which were identified as radial glial fibres. This expression pattern of keratan sulphate spatiotemporally corresponded well to the formation of the fovea isthmi, a groove separating the mesencephalon from the metencephalon. These results suggest that carbohydrates including keratan sulphate on PTPζ isoforms play important roles in brain development by modulating the cell-cell and/or cell-substrate interactions mediated by these molecules.     

Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure]

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.     

A case of double cancer: renal cell carcinoma and transitional cell carcinoma of urinary bladder

This is a case report on a patient with double cancer of kidney and urinary bladder. The patient was a 65-year-old female, and she was admitted with the chief complaint of gross hematuria and right flank pain. After careful examinations, she was diagnosed with right nonfunctioning kidney caused by invasive bladder cancer. Computerized tomography incidentally revealed a mass in the upper pole of the left kidney. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. She was diagnosed with double cancer of bladder and left kidney. Owing to the damage of the right renal function, left partial nephrectomy, total cystectomy, right nephroureterectomy and left ureterocutaneostomy were performed. According to DMSA scintigraphy measured 15 days later, the uptake value of the left kidney was 13.25%, compared to the preoperative value of 25.62%. To date, this case is 36th reported case in Japan.