To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.
The pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment were compared with those in healthy volunteers, and the factors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plasma concentration of tamsulosin was measured by a combination of equilibrium dialysis and liquid chromatography tandem mass spectrometry methods to examine the effect of protein binding on the pharmacokinetics of tamsulosin. Mean values for maximum concentration (C max ) and area under the concentration—time curve (AUC) of total drug (C max,t and AUC 1 in patients with renal impairment were 73% and 211% greater, respectively, than those in healthy volunteers. Mean C max and AUC of unbound drug (C max,u and AUC u ), however, were almost the same in the two groups. A high correlation was found between α 1 ‐acid glycoprotein (α 1 ‐AGP) concentration and AUC t , but no correlation was found between α 1 ‐AGP concentration and AUC u,0–36 or between creatinine clearance (Cl CR ) and AUC u,0–36 . These results show that in patients with renal impairment, the pharmacokinetics of tamsulosin are affected by the change in protein binding that is associated with alteration of plasma α 1 ‐AGP concentration, but are not largely affected by the decrease in the renal excretion. Although total tamsulosin levels increased as plasma protein binding increased, unbound tamsulosin levels (which are directly associated with the pharmacologic effects) remained unchanged in these patients.
A new anti-inflammatory, analgesic and antipyretic drug MK-647 was given orally in varying doses to a total of thirteen healthy Japanese volunteers for the observation of its influence on the findings of their physiological functions, heamtological tests, urinary analysis and sero-biochemical tests. At the same times, surveys were made on the changes produced in its blood level, urinary excretion and analgesic effects.As the result, no abnormality was observed on the physiological functions except an increase in the bowel sound provided the dosage employed was below 500mg at a time. This enhancement of the bowel sound, however, indicates a possibility for the development of gastrointestinal side effects.As for laboratory tests, an increase in alkaline phophatase was observed. A care should be taken on this matter when carrying out clinical studies in the future.Accumulation may be negated in view of the change in its blood level, however. Compared with acetylsalicylic acid, its effect was rather delayed in onset and lasted longer. Satisfactory clinical effect may be expected with administration twice a day.
To clarify mechanisms involved in the carcinogenesis of multiple oesophageal squamous cell carcinoma, the expression of p53 protein in 46 lesions surgically excised from 13 Japanese patients was investigated immunohistochemically and the relation of p53 protein accumulation to the patient’s history of alcohol consumption and cigarette smoking was analyzed. p53 protein accumulation was observed in 13 main lesions, that is in 6 (85.7%) of 7 subjects with a history of heavy drinking and smoking, but only in 1 (16.7%) of 6 with no such history (Fisher’s exact test, p = 0.025). As regards the 46 lesions, p53 protein accumulation was evident in 22 (88.0%) of 25 lesions of the high-risk patients, but in 7 (33.3%) of 21 lesions of the other subjects (Fisher’s exact test, p < 0.001). p53 protein accumulation was similarly recognized in all oesophageal lesions in 5 of 7 high-risk patients. Thus, use of both alcohol and cigarettes is clearly associated with a high frequency of p53 protein accumulation in multiple oesophageal squamous cell carcinoma present at the same time. These findings are considered to support the concept of field carcinogenesis of the oesophagus.
An α-mannosidase was purified from developing Ginkgo biloba seeds to apparently homogeneity. The molecular weight of the purified α-mannosidase was estimated to be 120 kDa by SDS–PAGE in the presence of 2-mercaptoethanol, and 340 kDa by gel filtration, indicating that Ginkgo α-mannosidase may function in oligomeric structures in the plant cell. The N-terminal amino acid sequence of the purified enzyme was Ala–Phe–Met–Lys–Tyr–X–Thr–Thr–Gly–Gly–Pro–Val–Ala–Gly–Lys–Ile–Asn–Val–His–Leu–. The α-mannosidase activity for Man5GlcNAc1 was enhanced by the addition of Co2+, but the addition of Zn2+, Ca2+, or EDTA did not show any significant effect. In the presence of cobalt ions, the hydrolysis rate for pyridylaminated Man6GlcNAc1 was significantly faster than that for pyridylaminated Man6GlcNAc2, suggesting the possibility that this enzyme is involved in the degradation of free N-glycans occurring in developing plant cells (Kimura, Y., and Matsuo, S., J. Biochem., 127, 1013–1019 (2000)). To our knowledge, this is the first report showing that plant cells contain an α-mannosidase, which is activated by Co2+ and prefers the oligomannose type free N-glycans bearing only one GlcNAc residue as substrate.
