Influences of angiogenesis and lymphangiogenesis on cancerous invasion in experimentally induced tongue carcinoma

BACKGROUND: Although it is clear that dissemination via the blood system involves angiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. The purpose of this study was to elucidate changes in tumor blood and lymph vessels in cases involving the invasion of squamous cell carcinoma in the oral cavity, and its significance. Blood and lymph vessels densities in tongue carcinomas induced in hamsters were investigated. METHODS: Tongue cancer was induced by abrading the right margin of the tongue of each hamster with an endodontic barbed broach and subsequently applying 1.0% 9,10-dimenthl-1,2-benzanthracene (DMBA) dissolved in acetone, three times a week, at the same site. Fresh frozen sections were prepared and blood vessels stained blue by perfusion with Coomassie Brilliant Blue and lymph vessels stained brown for 5'-nucleotidase. The effects on the blood vessels and lymph vessels were observed. RESULTS: The results showed that blood and lymph vessel densities were greater in the advanced carcinoma tissues than in normal tissue. These were compared in terms of the mode of cancer invasion. As tumor invasion progressed, the blood vessel density decreased but lymph vessel density tended to be higher in high-degree tumor invasion than in low-degree tumor invasion. The expression of vascular endothelial growth factor-C was seen more frequently as tumor invasion progressed. CONCLUSIONS: The present findings indicated that angiogenesis and lymphangiogenesis are affected by cancerous invasion.     

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.     

A case report of spinal epidural hematoma complicated after open heart surgery]

The authors reported the first case of acute spinal epidural hematoma (SEH) developed after open heart surgery. The patient was noticed that her legs felt weak and numb on the first postoperative day evening. On the next day morning, neurological examination revealed that flaccid paralysis of both legs and also loss of all sensory perception below the level of Th-6 spine bilaterally. The prolonged effect of anesthesia and painless onset made delayed recognition of the lesion. SEH (Th5-7) was diagnosed with MRI and decompressive surgery was immediately done, sixty hours after the beginning of cardiac operation. But in this case neurological deficits were not changed. We concluded that a routine diagnostic approach was very important procedure to find out this serious complication for all patients underwent open heart surgery in early period of its onset.     

Paucity of glutaminase-immunoreactive nonpyramidal neurons in the rat cerebral cortex.

Glutaminase has been considered to be a synthesizing enzyme of transmitter glutamate in pyramidal neurons of the cerebral cortex. In the present study, an attempt was made to examine with a double immunofluorescence method whether or not nonpyramidal neurons of the cerebral cortex are immunoreactive for glutaminase. Glutaminase was stained with mouse anti-glutaminase IgM and FITC-labeled anti-[mouse IgM] antibody. In the same section, parvalbumin (PA), calbindin (CB), choline acetyltransferase (CAT), vasoactive intestinal polypeptide (VIP), corticotropin releasing factor (CRF), cholecystokinin (CCK), somatostatin (SS), or neuropeptide Y (NPY) was visualized as a marker for nonpyramidal neurons with an antibody to each substance, biotinylated secondary antibody and Texas Red-labeled avidin. Virtually no glutaminase immunoreactivity was seen in PA-, CB-, CAT-, VIP-, CRF-, CCK-, SS-, or NPY-immunoreactive neuronal perikarya in the neocortex and mesocortex (cingulate and retrosplenial cortices), although it was detected in a few PA-, CB-, VIP-, CCK-, SS-, or NPY-immunoreactive nonpyramidal neurons in the piriform, entorhinal, and hippocampal cortices. PA- and CB-positive neurons have been reported to constitute the major population of GABAergic neurons in the cerebral cortex. Thus, the present results, together with the previous reports, suggest that most GABAergic, cholinergic and peptidergic nonpyramidal neurons in the neo- and mesocortex do not contain glutaminase.     

Differential Effects of Etomidate and Midazolam on Vascular Adenosine Triphosphate-sensitive Potassium Channels: Isometric Tension and Patch Clamp Studies

Background: The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity.

Methods: In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2[DELTA]C36 channels), and (4) mutant Kir6.2[DELTA]C36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2[DELTA]C36-K185Q channels).

Results: Etomidate (>= 10-6 m), but not midazolam (up to 10-6 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10-8 m; maximum inhibitory concentration: 1.22 x 10-4 m). Etomidate (>= 3 x 10-6 m), but not midazolam (up to 10-4 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10-5 m and 1.52 x 10-5 m, respectively. Etomidate (10-5 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2[DELTA]C36 channels, and Kir6.2[DELTA]C36-K185Q channels with equivalent potency.     

The metabolism of peptide leukotrienes in the lung may affect their coronary vasoconstrictive effect in anesthetized dogs

The deteriorative effect of peptide leukotrienes (LTs) on the coronary circulation are well known. On the other hand, it has been recognized that some of these prostanoids are metabolized in the pulmonary vascular bed. To clarify the influence of the metabolism of LTs in the lung on their effects to the coronary circulation, we compared the changes of coronary circulation parameters by leukotriene D4 (LTD4) and C4 (LTC4) administered (5 mcg/kg) into the right atrium (RA) and the left atrium (LA) in 8 mongrel dogs. After the administration of LTD4 and LTC4, significant reduction of coronary blood flow (LTD4-RA 65.8 +/- 3.4%, LTD4-LA 54.8 +/- 2.3%, LTC4-RA 64.3 +/- 3.9%, LTC4-LA 66.9 +/- 3.7%) and elevation of coronary vascular resistance (LTD4-RA 130.5 +/- 8.2%, LTD4-LA 157.3 +/- 6.1%, LTC4-RA 138.7 +/- 8.0%, LTC4-LA 129.5 +/- 10.1%) were recognized. The effect of LTD4, administered into the left atrium was significantly greater than that administered into the right atrium (p less than 0.05). The difference between right and left atrial administration was not statistically significant, although a tendency for the effect to be greater with right atrial administration than left was recognized. The LTC4 concentration in aortic blood measured by radioimmunoassay was significantly lower in right atrial administration than left (p less than 0.05). These results suggested that LTD4 was metabolized and inactivated in the lung during its passage through the pulmonary circulation, and LTC4 was not only inactivated but also converted to LTD4 and activated in the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microplate hybridization for Borna disease virus RNA in human peripheral blood mononuclear cells.

We developed a simple and sensitive microplate hybridization procedure with which to identify Borna disease virus cDNA in amplified products from human peripheral blood mononuclear cells. The mean values for the positive PCR products were significant compared with those for any of the negative products, indicating that this method can be applied to rapidly diagnose a large number of clinical specimens.     

HeLa cell invasiveness and O antigen of Shigella flexneri as separate and prerequisite attributes of virulence to evoke keratoconjunctivitis in guinea pigs.

Many rough mutants selected from isogenic smooth virulent and avirulent strains of Shigella flexneri were examined for virulence, using tissue culture infection and Sereny tests. Many of the rough mutants isolated from a virulent smooth strain were capable of penetrating tissue culture cells but incapable of producing a positive Sereny test. In contrast, we could not obtain from smooth avirulent strains any rough mutants capable of penetrating HeLa cells. Chemical analysis of lipopolysaccharide of some representative rough strains showed several patterns of sugar composition with a range of from Ra to Re chemotypes. There was no correlation between HeLa cell invasiveness and chemotypes of lipopolysaccharides, thus indicating little significance of oligosaccharides of the rough core as well as O antigens in the ability of S. flexneri to penetrate HeLa cells. When these invasive rough strains were given O antigen genes from a smooth avirulent Shigella Hfr strain, most of the transconjugants that expressed O antigens regained the ability to evoke keratoconjunctivitis in guinea pigs. We also examined the chromosomal loci of HeLa cell invasion by transferring carbohydrate fermentation genes of Escherichia coli K-12 Hfr and found two chromosomal loci, the rha and lac-gal regions, which control the ability to penetrate HeLa cells. These results suggested that O antigens and ability to penetrate tissue culture cells are independent and prerequisite attributes of virulence in Shigella flexneri to evoke keratoconjunctivitis in guinea pigs.