Contrast-enhanced MR angiography of the carotid artery using 3D time-resolved imaging of contrast kinetics: comparison with real-time fluoroscopic triggered 3D-elliptical centric view ordering

PURPOSE: To evaluate contrast-enhanced MR angiography using the 3D time-resolved imaging of contrast kinetics technique (3D-TRICKS) by direct comparison with the fluoroscopic triggered 3D-elliptical centric view ordering (3D-ELLIP) technique. METHODS: 3D-TRICKS and 3D-ELLIP were directly compared on a 1.5-Tesla MR unit using the same spatial resolution and matrix. In 3D-TRICKS, the central part of the k-space is updated more frequently than the peripheral part of the k-space, which is divided in the slice-encoding direction. The carotid arteries were imaged using 3D-TRICKS and 3D-ELLIP sequentially in 14 patients. Temporal resolution was 12 sec for 3D-ELLIP and 6 sec for 3D-TRICKS. The signal-to-noise ratio (S/N) of the common carotid artery was measured, and the quality of MIP images was then scored in terms of venous overlap and blurring of vessel contours. RESULTS: No significant difference in mean S/N was seen between the two methods. Significant venous overlap was not seen in any of the patients examined. Moderate blurring of vessel contours was noted on 3D-TRICKS in five patients and on 3D-ELLIP in four patients. Blurring in the slice-encoding direction was slightly more pronounced in 3D-TRICKS. However, qualitative analysis scores showed no significant differences. CONCLUSION: When the spatial resolution of the two methods was identical, the performance of 3D-TRICKS was found to be comparable in static visualization of the carotid arteries with 3D-ELLIP, although blurring in the slice-encoding direction was slightly more pronounced in 3D-TRICKS. 3D-TRICKS is a more robust technique than 3D-ELLIP, because 3D-ELLIP requires operator-dependent fluoroscopic triggering. Furthermore, 3D-TRICKS can achieve higher temporal resolution. For the spatial resolution employed in this study, 3D-TRICKS may be the method of choice.     

Sparse Distribution of Hepatocyte Growth Factor-producing Cells inside Hepatocellular Foci in Rats Treated with Hepatocarcinogens

The distribution of hepatocyte growth factor (HGF)–synthesizing cells in rat liver during development of glutathione S –transfcrasc P form (GST–P)–positive nodules after diethylnitrosamine initiation followed hy promotion with 2–acetylaminofluorene plus partial hepatectomy (PH) was investigated using in situ hybridization, HGF–produclng cells were iioii–parenchymal in nature, and were suspected to be mainly of Kupffer type. They were mostly located outside GST–P–positive lesions, in the surrounding parenchyma. In the oval cell proliferation phase 1 week after PH, they increased and they were mainly localized around the portal triads. It is concluded that HGF is directly involved in an endogenous paracrine growth pathway controlling proliferation in oval cells and in normal, hut not GST–P–positive, hepatocytes.     

Clinical Application of Serum Pepsinogen I and II Levels for Mass Screening to Detect Gastric Cancer

A considerable number of gastric cancers derive from stomach mucosa where chronic atrophic gastritis is severe and extensive. Based on the fact that the serum pepsinogen levels provide a precise measure of the extent of chronic atrophic gastritis, we have devised a mass screening method involving serum pepsinogen measurement to identify subjects at high risk of gastric cancer. In 1991, we screened 4,647 workers (male: 4,113, female: 534, mean age: 49.0 years) at a Japanese company using this method. Out of 875 subjects (18.8%) with a serum pepsinogen I level of less than 50 μg/liter and a pepsinogen I/II ratio of less than 3.0, 676 subjects (14.5%) were selected for further investigation by endoscopy. This led to the detection of four subjects (0.086%) with gastric cancer (three in an early stage) and four subjects with adenoma. The cancer detection rate of this new screening method was comparable, and in some respects superior, to that of the traditional barium X-ray screening. Since the incidence of test-positive subjects was as low as 10% amongst subjects aged less than 40, this screening method appears to be especially useful for screening of younger generations. The new method is less expensive than the traditional barium X-ray and subjects experience little discomfort. Further, many serum samples can be quickly measured simultaneously. The results of this study have indicated that serum pepsinogen screening provides a valuable method for detecting gastric cancers.     

Suppression of manganese superoxide dismutase augments sensitivity to radiation, hyperthermia and doxorubicin in colon cancer cell lines by inducing apoptosis

Increased expression of manganese superoxide dismutase (Mn-SOD), one of the mitochondrial enzymes involved in the redox system, has been shown to diminish the cytotoxic effects of several anti-cancer modalities, including tumour necrosis factor-alpha, ionizing radiation, certain chemotherapeutic agents and hyperthermia. We asked if Mn-SOD is a potential target to augment the sensitivity of cancer cells to various anti-cancer treatments and for this we established stable Mn-SOD antisense RNA expressing cell clones from two human colon cancer cell lines, HCT116 (p53 wild-type) and DLD1 (p53 mutant-type). Suppression of Mn-SOD in HCT116 was accompanied by an increased sensitivity to radiation, hyperthermia and doxorubicin, as compared with findings in controls. The mitochondrial permeability transition, as measured by a decrease of the mitochondrial transmembrane potential was more intensely induced by radiation in HCT116 antisense clones than in the control, an event followed by a greater extent of DNA fragmentation. Apoptosis was also induced by hyperthermia more intensely in HCT116 antisense clones than in the control. On the other hand, DLD1 antisense clones did not exhibit any enhancement of sensitivity to any of these treatments. These data support the possibility that inhibition of Mn-SOD activity renders colon cancer cells with wild-type p53 susceptible to apoptosis induced by radiation, hyperthermia and selected anti-cancer drugs. Therefore, we suggest that Mn-SOD could be a target molecule to overcome the resistance to anti-cancer treatments in some colon cancer cells carrying wild-type p53.     

The protease from Vibrio Cholerae nicks arginine at position 192 from the N-terminus of the heat-labile enterotoxin a subunit from enterotoxigenic Escherichia Coli

It was examined where a protease purified from Vibrio cholerae might nick the heat-labile enterotoxin (LT) A subunit from enterotoxigenicEscherichia coli.LT was digested by the protease and contained a fragment which had the same mobility on SDS-PAGE as that of the Al fragment of LT digested by trypsin. The biological activity of LT by this protease was also identical to that of LT by trypsin. The amino acid sequence of the N-terminus of the A2-like fragment was Thr-Ser-Thr-Gly, which corresponded to the sequence from 193 to 196 of the A subunit.These data suggest that this protease, like trypsin, nicks arginine at position 192 from the N-terminus of the A subunit and that the biological activation of LT by this protease is similar to that by trypsin.Corresponding author.     

Pulmonary toxicity induced by intratracheal instillation of Asian yellow dust (Kosa) in mice

Asian yellow dust (Kosa) causes adverse respiratory health effects in humans. The objective of this study was to clarify the lung toxicity of Kosa. ICR mice (5 weeks of age) were administered intratracheally with Kosa samples-two samples from Maowusu desert and Shapotou desert, one sample consisted of Shapotou Kosa plus sulfate, and natural Asian dust (NAD) from the atmosphere of Beijing-at doses of 0.05, 0.10 or 0.20mg/mouse at four weekly intervals. The four Kosa samples tested had similar compositions of minerals and concentrations of elements. Instillation of dust particles caused bronchitis and alveolitis in treated mice. The magnitude of inflammation was much greater in NAD-treated mice than in the other particles tested. Increased neutrophils, lymphocytes or eosinophils in bronchoalveolar lavage fluids (BALF) of treated mice were dose dependent. The number of neutrophils in BALF at the 0.2mg level was parallel to the content of β-glucan in each particle. The numbers of lymphocytes and eosinophils in BALF at the 0.2mg level were parallel to the concentration of SO(4)(2-) in each particle. Pro-inflammatory mediators-such as interleukin (IL)-12, tumor necrosis factor-(TNF)-α, keratinocyte chemoattractant (KC), monocyte chemotactic protein (MCP)-l and macrophage inflammatory protein-(MIP)-lα in BALF-were greater in the treated mice. Specifically, NAD considerably increased pro-inflammatory mediators at a 0.2mg dose. The increased amounts of MlP-lα and TNF-α at 0.2mg dose corresponded to the amount of β-glucan in each particle. The amounts of MCP-l or IL-12 corresponded to the concentration of sulfate (SO(4)(2-)) at a 0.2mg dose. These results suggest that inflammatory lung injury was mediated by β-glucan or SO(4)(2-), which was adsorbed into the particles, via the expression of these pro-inflammatory mediators. The results also suggest that the variations in the magnitude of inflammation of the tested Kosa samples depend on the amounts of these toxic materials.     

Maximum permissive dosage of lactose and lactitol for transitory diarrhea, and utilizable capacity for lactose in Japanese female adults

This study aims to estimate the tolerable lactose intake which can be utilized in the digestion by lactase and in the fermentation by intestinal microbes in Japanese female adults. The first, the maximum permissive dosage of lactose not to induce transitory diarrhea was estimated based on the oral ingestion of lactose at several dose levels in all the subjects, and compared with that of lactitol which is not hydrolyzed by digestive enzymes. A second lactose tolerance test involving 10 g and 30 g of lactose was carried out in 10 subjects showing resistance to diarrhea, and serum glucose and insulin levels and the amount of hydrogen excreted in the breath were measured for comparison with those of glucose and lactitol. Subjects were 43 Japanese female adults (average: age 20.5+/-2.1 y, weight 51.3+/-5.1 kg) who had not been diagnosed as having either hypolactasia or being lactose intolerant. Serum glucose and insulin levels were scarcely elevated following the ingestion of both 10 g and 30 g of lactose, while the amount of hydrogen excreted in the breath was greatly increased following the ingestion of 30 g of lactose, but these levels were less following the ingestion of 10 g of lactose. In contrast, the ingestion of 15 g of glucose significantly increased blood glucose and insulin levels, while no hydrogen was detected in the breath. The maximum permissive dosage of lactose not to induce transitory diarrhea was 0.72 g/kg of body weight and that of lactitol was 0.36 g/kg of body weight in Japanese adults. The digestive capacity of lactase is less than 10 g of lactose by single ingestion, while intestinal microflora are able to ferment approximately 20-30 g of lactose. In addition, the ingestion of more than 10 g of lactose might be contributed as prebiotics.     

Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model

Diabetic nephropathy is one of the major microvascular complications in diabetes and is the leading cause of end-stage renal disease worldwide. Among various factors, angiogenesis-associated factors such as vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-2 are involved in the development of diabetic nephropathy. We previously reported the therapeutic efficacy of antiangiogenic tumstatin peptide in the early diabetic nephropathy model. Here, we examine the effect of endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen, in preventing progression in the type 1 diabetic nephropathy mouse model. Endostatin peptide did not affect hyperglycemia induced by streptozotocin (STZ). Glomerular hypertrophy, hyperfiltration, and albuminuria were significantly suppressed by endostatin peptide (5 mg/kg) in STZ-induced diabetic mice. Glomerular mesangial matrix expansion, the increase of glomerular type IV collagen, endothelial area (CD31(+)), and F4/80(+) monocyte/macrophage accumulation were significantly inhibited by endostatin peptide. Increase in the renal expression of VEGF-A, flk-1, Ang-2, an antagonist of angiopoietin-1, transforming growth factor-beta1, interleukin-6, and monocyte chemoattractant protein-1 was inhibited by endostatin peptide in diabetic mice. Decrease of nephrin mRNA and protein in diabetic mice was suppressed by treatment with endostatin peptide. The level of endostatin in the renal cortex and sera was increased in diabetic mice. Endogenous renal levels of endostatin were decreased in endostatin peptide-treated groups in parallel with VEGF-A. Although serum levels of endostatin were decreased in the low-dose endostatin-peptide group, high-dose administration resulted in elevated serum levels of endostatin. These results demonstrate the potential use of antiangiogenic endostatin peptide as a novel therapeutic agent in diabetic nephropathy.