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Biomedical subjects

A Ouchi

Publications and source records attributed to A Ouchi.

At least 19 recordsLinked to original sources

Detection of the three common mutations of adeninephosphoribosyltransferase deficiency among Japanese.

We analyzed DNA from six Japanese patients with adenine phosphoribosyltransferase (APRT) deficiency who developed 2,8-dihydroxyadenine (DHA) urolithiasis. These six patients were selected for DNA analysis since they were expected to possess allele(s) with mutations other than two known abnormalities, i.e. a missense mutation at codon 136 (APRT*J allele) and a nonsense mutation at codon 98. In three of the six patients an insert of four bases CCGA was detected in exon 3 by sequencing clones obtained from the genomic DNA. In two of the three patients, both of the two alleles had this mutation (homozygotes) while the other patient had the APRT*J allele in addition to the allele with the 4-base insertion. To search for mutations other than the above three defined germline mutations, we amplified a genomic DNA segment including all the 5 exons of the APRT gene by PCR and cloned it into a plasmid. After selecting recombinant plasmids containing neither of the three defined mutations, we sequenced the entire APRT exons and introns. Abnormalities were found in neither the coding regions nor the exon-intron junctions. Disease-related mutations in these mutant alleles may exist in either 5' or 3' flanking sequences and remain to be elucidated.

Adenine Phosphoribosyltransferase

Undifferentiated carcinoma of the duodenal ampulla.

This report demonstrates a case of undifferentiated carcinoma of the duodenal ampulla. A 74-year male experienced jaundice lasting for 3 weeks. An upper gastrointestinal series demonstrated a polypoid, ovoid filling defect in the second portion of the duodenum, and duodenoscopy disclosed a protruding mass involving the orifice of the papilla of Vater. Cholangiography demonstrated obstruction due to compression in the terminal common bile duct. Pylorus-preserving pancreatoduodenectomy was performed on the diagnosis of ampullary carcinoma. The gross specimen showed a polypoid mass, measuring 3.5 cm in diameter, in the ampulla, located mainly in the duodenal submucosal layer and invading the terminal common bile duct. Histologically, the tumor was small cell type, undifferentiated carcinoma, arising from the duodenal epithelium adjacent to the ampulla.

Aged

Comparison of false negative rates among breast cancer screening modalities with or without mammography: Miyagi trial.

False negative rates were compared in two screening modalities, physical examination with or without mammography, in an intervention study for women aged over 50 in Miyagi Prefecture. Thirty-five breast cancers were detected in 12,515 subjects who participated in the trial consisting of physical examination and mammography, whereas 44 breast cancers were detected in 50,105 subjects who received physical examination alone, so that the detection rates were 0.28% and 0.09%, respectively. Among 50,061 subjects who received physical examination alone, 8 women were diagnosed as having breast cancer within 12 months after the screening, while only one of 12,480 screenees receiving the combined modality was so diagnosed, implying false negative rates of 15.4% and 2.8%, respectively. When the screening sensitivity in the combined system was analyzed according to each single modality, the false negative rate provided by physical examination with mammography turned out to be 2.8%, significantly lower than that (33.3%) by the physical examination alone. Minimal breast cancers represented 25.7% of all screen-detected cancers in the combined modality, compared with 9.1% in the modality without mammography. The trial thus indicates that physical examination combined with mammography may be an appropriate modality for breast cancer screening in women aged over 50 on the basis of screening sensitivity.

Aged

[A randomized trial of intrahepatic infusion chemotherapy for unresectable colorectal liver metastases. Sendai Study Group].

A prospective, controlled randomized trial of hepatic arterial infusion of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC) [FAM group] versus 5-FU, epirubicin (EPIR) and MMC [FEM group] in patients with unresectable liver metastasis from colorectal cancer is reported. No objective response was observed in FAM group (n = 6), while two objective responses, 1 complete and 1 partial (22.2%), were achieved in FEM group (n = 9). There was no significant difference in the 50% survival period between the two groups (468 days in FAM group (n = 8) versus 462 days in FEM group (n = 10). Long survival over 2 years was observed in FEM group, but not in FAM group. Toxicities were recorded in 50% (3/6) of FAM group, and 80% (8/10) of FEM group, but they were mild and well tolerated. In conclusion, although there was no significant difference in clinical effects between the two groups, the use of EPIR instead of ADR in combination with 5-FU and MMC might be favorable for intrahepatic infusion chemotherapy because responders and long-term survival were exclusively observed in FEM group.

Adult

[Functional and phenotypic analysis of tumor infiltrating lymphocytes derived from solid tumors and effusion associated lymphocytes in malignant ascites cultured in recombinant interleukin 2].

Tumor infiltrating lymphocytes (TIL) and effusion associated lymphocytes (EAL) were isolated from 7 human solid tumors and 6 malignant ascitic fluids respectively, and cultured in rIL2 (700JRU/ml)-containing medium. Long-term culture (> 14 days) of separated lymphocytes with exponential increase in cell number was achieved in 5 EAL-cultures, whereas in only 2 TIL-cultures. rIL2-expanded TIL and EAL manifested significant cytotoxicity in a 4-hrs chromium release assay. The maximum NK and LAK activity were reached 21 days and 14 days after starting incubation with rIL2 respectively, followed by a rapid decrease in cytolytic potential without declining growth rate of the cells. Phenotypic analysis showed the majority of the freshly isolated TIL and EAL were CD3+ T cells, and CD16+ NK cells were rarely identified in TIL. With induction of LAK cell activity, CD8+ T cells predominantly increased in TIL-cultures, while both CD4+ and CD8+ T cells and CD16+ NK cells were increased in EAL cultures. In activated TIL most cytolytic activity was found in CD8+ T cells, in contrast CD16+ NK cells were responsible for it in activated EAL. These results indicated that EAL and TIL have similar properties in which they coexist with cancer cells at tissue level and were capable of expanding and acquiring LAK cell activity in the presence of rIL2, but apparently differ in their mechanism of rIL2-mediated activation.

Adult

[The efficacy of intra-arterial infusion chemotherapy in patients with non-resectable liver metastasis from colorectal cancer--a randomized study comparing FAM versus FEM].

The efficacy of FAM (5-FU, ADM, MMC) chemotherapy was compared with that of FEM (5-FU, EPIR, MMC) chemotherapy, in which the EPIR dose was about 1.3 times the ADM dose, by hepatic arterial infusion. Twenty-one patients with unresectable hepatic metastasis from colorectal cancer were the subjects of this multi-institutional randomized study. The response rate in evaluable 15 patients was 0% (0/6) in FAM group and 22% (2/9) in FEM group, with a 50% survival time of 15.3 months in FAM group and 15.1 months in FEM group. The major toxicities were gastrointestinal, together with hepatic dysfunction, both of which were not serious. Total incidence of > or = grade 2 toxicities was 50% (3/6) in FAM group and 80% (8/10) in FEM group. There was no statistical difference between the two groups in response rate, 50% survival time and toxicities. The clinical results of FAM and FEM were therefore considered equal, and an expected improvement in efficacy by increasing the EPIR dose was not confirmed. However, two patients in FEM group showed an objective response not observed in FAM group; one of them showed CR and survived about 3 years. These findings seem to suggest the efficacy of FEM hepatic arterial infusion chemotherapy for treatment of unresectable hepatic metastasis from colorectal cancer.

Adult

[Relationship between venous invasion and hematogenous metastasis in the colorectal cancer patients].

We investigated the correlation between venous invasion and hematogenous metastasis. In thirteen patients with colorectal carcinoma, depth of invasion (ss.s or a1.a2) was the same. Four cases had hepatic metastasis at operation (group A), 3 cases were identified with hematogenous recurrence after operation (group B), and 6 cases were disease free over 10 years after operation (group C). Specimens were all step-sectioned and serial sections were stained both with HE and EM. Results were as follows. 1. Venous invasion was found in all cases and average rates of venous invasion (ARVI) of groups A and B were higher than that of group C (A; 7.8%, B; 6.3%, C; 2.1%, p less than 0.05). 2. In ss.s layer, ARVI of group A and B were higher than that of group C (A; 6.1%, B; 6.2%, C; 1.5%, p less than 0.05). 3. Rates of venous invasion to larger veins (diameter greater than 200 microns) were higher in group A than in others (A; 53.5%, B; 25.6%, C; 7.9%, p less than 0.05), and those to the middle-sized veins (diameter; 50-200 microns) were higher in group B than in others. These facts suggest that cancer invasion to the veins located in ss.s (a1.a2) layer or ranged in diameter over 200 microns relates to hematogenous metastasis.

Colorectal Neoplasms

Bone metabolism following gastric surgery: microdensitometry and single-photon absorptiometry.

The impairment of bone metabolism was investigated in patients who underwent gastrectomy or vagotomy with drainage two or more years ago. Serum biochemical analysis, microdensitometry of the 2nd metacarpal bone, and measurements of bone mineral content of the radius (measured 1/3 distally) using single-photon absorptiometry were performed at follow-up examination. Although serum levels of calcium, phosphorus and alkaline phosphatase were within normal range, alkaline phosphatase levels were slightly higher for the Billroth II group than for Billroth I. Twenty-eight of 50 gastrectomy cases (56%), and four of 10 vagotomy cases (40%) showed pathologically thin bone: microdensitometric (MD) scores were greater than 3. The Billroth II group showed a far higher frequency of greater MD scores than Billroth I. The MD scores showed significant positive relationship with the age at follow-up, but did not correlate well with the length of the postoperative period. Radial bone mineral content (BMC) was lower in patients with Billroth II anastomosis, or with total or proximal gastrectomy, than in those undergoing Billroth I. These results suggest that metabolic bone disorders following gastric surgery can be detected by MD score and BMC of appendicular bones. However, there was not sufficient resolution with these parameters to detect any bone changes in patients treated with active vitamin D3.

Adult

[Clinicopathological study on minute- and small-gastric cancer--growing pattern in incipient phase of gastric cancer development and its clinical significance].

A clinicopathological study was performed on 13 cases of minute gastric cancer (14 lesions) with a diameter less than 5.0 mm and 33 cases of small gastric cancer (34 lesions) with a diameter between 5.1 mm and 10.0 mm. The incidence of flat lesions, multiple cancer and differentiated adenocarcinoma was more frequent in minute and small gastric cancer than in ordinary early gastric cancer with a diameter greater than 11 mm. The incidence of submucosal invasion in single cancer case (30.6%, 11/36) was significantly higher than that in multiple cancer case (8.3%, 1/12). The size of the smallest lesion invading the submucosal layer was 3.2 mm in diameter. Histological examination of the cancer lesions revealed that differentiated adenocarcinoma began to develop at the deeper mucosal layer, while undifferentiated adenocarcinoma did at the superficial mucosal layer. It was also demonstrated that the differentiated adenocarcinoma invaded the submucosal layer through the natural crevices of lamina muscularis mucosa. Pathological and mucohistochemical analysis of both the cancer cells and the surrounding mucosal tissue showed that intestinal metaplasia of the mucosa, especially mucohistochemically incomplete type metaplasia seemed to have close relation with the histogenesis of the differentiated adenocarcinoma.

Adenocarcinoma

Histologic infiltrating pattern of gastric microcarcinoma by means of serial sections.

Two hundred eighty serial histologic sections, 5 micron thick, were made of a very small gastric carcinoma with submucosal invasion in order to assess the initial infiltrating pattern into the submucosa, as well as the growth therefrom. The small carcinoma infiltrated into the submucosa through four independent small channels, 0.02 to 0.05 mm2 in size, despite its small spread (3 mm in diameter) on the mucosal layer. Each small channel always was accompanied by the small blood vessels penetrating the lamina muscularis. The size of carcinoma in submucosa grew further to reach 3 to 10 times small infiltrating sites of lamina muscularis mucosa. The growth pattern of the carcinoma in the submucosa, therefore, seemed to be an "expanded balloon." Moreover, a small but distinct vascular invasion could be demonstrated within the balloon, suggesting a possible vascular metastasis.

Carcinoma

[Clinicopathological study of a malignant lesion in the remnant stomach].

Thirty-six cases of malignant lesion in the remnant stomach were studied clinicopathologically. Ten had been surgically managed as benign lesions and eight were suspected of being metachronous multiple gastric cancer. The pathological characteristics of the malignant lesions and the operation interval (mostly more than 10 years) were similar in these two groups. Although malignant lesion in the remnant stomach is difficult to differentiate clearly when there is no sufficient histological evidence, the operation interval of more than 10 years can be one of the criteria for differential diagnosis.

Adult

[Studies on the results of operations for carcinoma of the sigmoid colon].

Of 734 patients with colorectal cancer operated on during the past 21 years, 142 had carcinoma of the sigmoid colon. Curative resections were performed in 103 patients and non-curative resections in 22, the resection rate being 88.0%. Among 103 patients with curative resection, resection of the sigmoid colon was performed in 79, and their 5-year survival rate was 84.6%. Eight patients died within 5 years due to recurrence. Many of them had the constricting type macroscopically and Dukes C with positive lymph node metastasis. Therefore, in such cases, resection of the sigmoid colon with extended lymph node dissection or left hemicolectomy should be performed.

Adenocarcinoma

[Early stomach cancer derived from heterotopic glands--a case report].

A 69-year-old man with early gastric cancer derived from heterotopic glands in the submucosal layer is reported. Macroscopically, two flat elevated lesions were found on the anterior and posterior walls of the stomach; histologic examination revealed submucosal cystic glands in each lesion. Carcinoma was proved only in the deeper part of the submucosal glands on the anterior wall; no obvious cancerous change was confirmed in the overlying mucosa and heterotopic glands in the posterior wall.

Aged

[Clinico-pathological studies on multiple colorectal cancer].

Of 743 patients with colorectal cancer operated during the past 21 years, 52 with double cancer, excepting patients in whom the disease was associated with familial polyposis, were examined. A higher association of adenomas was noted in multiple carcinomas of the large intestine than in a single carcinoma. As most of the multiple carcinomas were located close to each portion, it is possible to resect the multiple tumors concomitantly during a single operative procedure. No recurrence or mortality was seen in patients with synchronous multiple carcinomas that coexisted with advanced and early cancers. However, all patients with two or more advanced cancers died a short time after the operation. In 66.7% of the cases the other organ involved in the double cancer was the stomach. When the cancers were in the early stage, long-term survival could be achieved even in the presence of synchronous double cancers. Despite the early detection of the primary cancer in metachronous double cancer, patients whose second cancer was in the advanced stage died shortly after the second operation.

Adult

[Clinicopathological evaluation of patients surviving stomach cancer for 10 years following gastrectomy].

The clinicopathological findings on 232 patients with advanced gastric cancer who survived longer than 10 years after curative surgery were reviews and compared with those on 287 patients who died within 5 years of their operation. There were significantly more 10-year survivors in the group whose tumor size was less than 5 cm, where the center was not located in the cardia, in patients without lymph node involvement, less vessel invasion and higher lymphocyte infiltration around the stroma of the cancerous nests. No statistical differences were observed with regard to patient age, sex, Borrmann classification, histological types and invasive patterns between 10-year survivors and patients who died less than 50 years postoperatively.

Female