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Biomedical subjects

Yasuo Imai

Publications and source records attributed to Yasuo Imai.

26 records · Page 2Linked to original sources

C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance.

Breast cancer resistance protein (BCRP) confers multidrug resistance to cancer cells against agents such as SN-38 (an active metabolite of irinotecan), mitoxantrone, and topotecan. Among 59 human tumor cell lines tested, 6 cell lines, A549, NCI-H460, KM-12, HT-29, OVCAR-5, and RPMI8226, showed high BCRP expression. BCRP cDNA was isolated from 11 cancer cell lines and three variant cDNAs [G34A substituting Met for Val-12 (V12M), C421A substituting Lys for Gln-141 (Q141K), and 944-949 deletion lacking Ala-315 and Thr-316 (delta315-6)] were identified. G34A and C421A variants were polymorphisms, and 944-949 deletion was a splicing variant. C421A BCRP-transfected PA317 cells showed markedly decreased protein expression and low-level drug resistance compared with wild-type BCRP-transfected cells when transfectants expressed similar levels of BCRP mRNA. G34A or 944-949-deleted BCRP-transfected PA317 cells showed similar or somewhat lower protein expression and drug resistance compared with wild-type BCRP-transfected cells. Of 124 healthy Japanese volunteers, 67 were wild-type, 48 were heterozygous, and 9 were homozygous for the C421A allele. These results suggest that some people possess the C421A polymorphic BCRP gene and express low amounts of Q141K BCRP. In addition to that, C376T polymorphism in exon 4 substituting stop codon for Gln-126 was found in 3 of the 124 general Japanese population. This C376T polymorphism may also have high impact because active BCRP protein will not be expressed from the C376T allele. Therefore, people with C376T and/or C421A polymorphisms may express low amounts of BCRP, and this low BCRP expression might result in hypersensitivity of normal cells to such anticancer drugs as irinotecan and mitoxantrone.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Sex difference and possible relationship to microvascular complications of serum prorenin levels in type 2 diabetic patients, measured by a novel antibody-activating direct enzyme kinetic assay.

Prorenin, a precursor of renin, was measured in sera from normal subjects and type 2 diabetic patients, using a newly developed antibody-activating direct enzyme kinetic assay. Levels of prorenin were examined in relationship to diabetic microangiopathies. The levels of antibody-activating direct prorenin (AAD-PR) were approximately 1.5-fold higher than levels of prorenin measured by a conventional enzyme-activating method. AAD-PR levels were significantly higher in males than in females and in diabetic patients than in normal subjects. Moreover, AAD-PR levels were higher in diabetic patients with microalbuminuria and even higher in those with macroalbuminuria. In normoalbuminuric diabetic patients, AAD-PR levels were higher in those with retinopathy. Furthermore, a significant positive correlation was seen between the AAD-PR levels and HbA(lc) in normoalbuminuric diabetic subjects without retinopathy. Thus, the determination of circulating serum prorenin measured as AAD-PR is related to glycemia and in type 2 diabetic patients may be a risk marker of diabetic microangiopathy. More studies are necessary to determine whether AAD-PR may actually predict the development of microangiopathy.

Adult↗

Histological analysis of the papilla after endoscopic papillary balloon dilation.

BACKGROUND/AIMS: Endoscopic papillary balloon dilation is an effective procedure in the management of bile duct stones and is believed to preserve the papillary function. The papillary architecture is also considered to be preserved. However, little is known about the effects of balloon dilation on papillary structure. The present study was conducted to elucidate these effects. METHODOLOGY: Since May 1994, endoscopic papillary balloon dilation was performed in 467 patients (407 patients for removal of bile duct stone, 57 for insertion of stent and 3 for baby cholangioscope). Of those, histological examinations were undertaken in 10 patients. The indications of endoscopic papillary balloon dilation were bile duct stone removal in 2 patients, stent insertion in 8. The specimens were obtained 2 to 63 weeks after endoscopic papillary balloon dilation during surgical operation in 6 patients and autopsy in 4 patients. Serial sections through the papilla were stained by hematoxylin and eosin and Masson's trichrome. The specimens were also obtained from 4 patients without biliary disease as control. RESULTS: No smooth muscle disruption nor architectural distortion was observed except for one patient who had mild disruption of smooth muscle caused by a biliary drainage tube. However, mild to moderate inflammation and fibrosis were seen in 9 patients and in 8, respectively. CONCLUSIONS: The papillary architecture is not affected by endoscopic papillary balloon dilation. This may imply that endoscopic papillary balloon dilation preserves papillary function.

Aged↗

"Duodenal intussusception" due to adenoma of the papilla of Vater.

The case of a 55-year-old woman with a pedunculate adenoma of the papilla of Vater is presented. Diagnostic imaging modalities including ultrasonography, CT scan, magnetic resonance of cholangiopancreatography, simultaneous duodenography and cholangiography, and angiography showed a giant tumor protruding intraluminally and moving forward in the duodenum by peristalsis. It had a duodenal intussusception-like appearance, with remarkable left-lower deviation of the common bile duct and major pancreatic duct in the papilla of Vater as far as the left side of the aorta. Episodes of jaundice or ileus were absent, probably because the tumor was mobile in the duodenum. As biopsy specimens showed no malignancy and intraductal ultrasonography in the common bile duct revealed no intraductal invasion of the tumor in the papilla of Vater, the patient underwent transduodenal papillectomy with papilloplasty with pancreatic ductoplasty. Pathological diagnosis of consecutive specimens was a papillary adenoma with moderate atypia and occasional tubular structure. There seems to be an exceptional subtype of the tumor in the papilla of Vater, like this case, demonstrating the duodenal intussusception-like appearance without prominent clinical symptoms.

Adenoma↗

Factors predisposing to poorly differentiated hepatocellular carcinoma and its recurrence.

BACKGROUND/AIMS: We investigated the clinical factors predisposing moderately or poorly differentiated hepatocellular carcinoma and analyzed which clinical and histological factors are associated with poorly differentiated hepatocellular carcinoma (HCC) recurrence. METHODOLOGY: Percutaneous fine-needle biopsy was taken from the liver tumor of 191 consecutive patients between January 1994 and September 1996. The histological degree of differentiation of hepatocellular carcinoma at the first time of initial treatment and at the time of second recurrence was classified according to the criteria of Edmondson and Steiner. RESULTS: At the time of the first therapy, 86 patients, 81, 24, and 0 patients had liver tumors classified as Edmondson (Ed), 1, 2, 3, and 4, respectively. The prognosis of patients with Ed-3/4 HCC was worse than and the tumor sizes were larger than that of Ed-1/2 HCC patients. Of the 167 patients classified as Ed-1/2 at the time of first therapy, HCC recurred in 95 of the patients during the mean follow-up period of 3.4 years. Multivariate analysis revealed that only tumor size (P=0.035) and TACE therapy (P=0.0009) were independently significant factors in predicting future Ed-3/4 or multiple HCC recurrence. CONCLUSIONS: Tumor size and TACE therapy were clinical predisposing factors for Ed-3/4 or multiple HCC recurrences.

Adult↗