PubMed HealthSearch

Biomedical subjects

A Sugita

Publications and source records attributed to A Sugita.

At least 19 recordsLinked to original sources

Two forms of avian(chicken) TATA-binding protein mRNA generated by alternative polyadenylation.

We have isolated and sequenced the cDNA encoding avian(chicken) TATA-binding protein (cTBP). The cTBP protein shows a significant homology to those of the other species, and especially its C-terminal region (180 amino acid residues) is identical to those of the vertebrates. By Northern blot analysis, we found that two transcripts with about 2.1 kb (cTBP0) and 2.7 kb (cTBP1) were expressed in various chicken tissues, though only one type of the TBP transcript was reported in vertebrates. A primer extension study demonstrated a single transcription start site. The analysis of the genomic structure of cTBP with the sequences of the two types of cTBP cDNAs(cTBP0 and cTBP1) revealed that the alternative polyadenylation generates two transcripts with different 3'untranslated regions (3'UTRs), indicating a putative role of the different 3'UTRs on the stability of cTBP mRNAs.

Amino Acid Sequence

ERC-55, a binding protein for the papilloma virus E6 oncoprotein, specifically interacts with vitamin D receptor among nuclear receptors.

VDR regulates gene expression in a ligand-dependent way by binding to cognate enhancer elements of target gene promoters. The ligand-dependent activation function, AF-2, of VDR is thought to require transcriptional co-activators/co-repressors together with basal transcriptional machinery. Using a yeast two hybrid system with VDR, we have isolated a mouse Ca(2+)-binding protein (designated as VAF1) specifically interacting in vivo and in vitro with VDR among nuclear receptors like RAR, RXR, ER and GR. VAF1 is a mouse homologue to human ERC-55, which has recently been shown to interact with human papillomavirus oncogenic protein, E6[1]. Unlike those of many previously identified co-activators, the VDR-VAF1 interaction was ligand-independent. Thus, VAF1 seems a putative VDR-specific cofactor modulating its function.

Amino Acid Sequence

Enhanced expression of PP1 gamma 1, a catalytic subunit isoform of protein phosphatase type 1, in invasive ductal carcinoma of the breast.

Breast cancer is one of the most common malignancies of women. Assessing the biological parameters of malignant tumors may facilitate predictions of clinical outcome. The expression of the three catalytic subunits of protein phosphatase (PP) type 1, PP1 alpha, PP1 gamma 1 and PP1 delta, as well as the one catalytic subunit of PP type 2, PP2AC, were examined in ten cases of mammary dysplasia, ten cases of fibroadenoma and 12 cases of invasive ductal carcinoma, using immunohistochemical analysis. Moreover, we measured the S-phase fraction of the cell cycle for use as a marker value of cell growth, using flow cytometric analysis. The percentage of proliferating cells that stained positive with antisera against PP1 gamma 1 was significantly higher in invasive ductal carcinoma than in mammary dysplasia and fibroadenoma. Furthermore, invasive ductal carcinoma showed a markedly high number of tumor cells in the S-phase of the cell cycle, as compared to mammary dysplasia and fibroadenoma. Our results indicate that PP1 gamma 1 may be involved in the accelerated growth of malignant cells in breast tumors.

Adult

Urinary changes in patients following restorative proctocolectomy.

Following restorative proctocolectomy, the physiological function of the large intestine to absorb water and electrolytes is lost. Therefore, the kidney plays an important role in adjusting the water and electrolyte balance along with the ileal pouch. The reservoir function of the ileal pouch, however, may affect the functional adaptation of urinary changes. To observe the functional adaptation of urinary changes in ileal pouch patients, their changes in urinary output and electrolytes were investigated. Urinary output, pH, and electrolytes were all measured at 1 month, 6 months, and 1 year after surgery in patients with a J-pouch (n = 30) and compared with those in patients who had undergone ileostomy (n = 11) and healthy controls (n = 22). In the patients with a J-pouch, the urinary output, pH, and sodium concentration were significantly lower than those of the controls at 1 month after the operation. However, they gradually increased to near the control values at 1 year. In patients with an ileostomy, the urinary output, pH, and sodium concentration were lower than the control values up to 1 year postoperatively, but the urinary uric acid concentration was higher than that in the controls in both groups up to 1 year. The patients who had persistent aciduria were given a citrate mixture (3g/day), which effectively normalized the aciduria and also possibly prevented urinary uric acid stone formation.

Adult

[Preservation of anal transitional zone in restorative proctocolectomy].

Since 1980, restorative proctocolectomy has been established for surgical therapy to ulcerative colitis. The crucial points of this procedure are mucosectomy of the anorectal mucosa and pouch anal anastomosis. Mucosectomy is often difficult due to long standing acute and chronic inflammation and incomplete microscopically and leakage of pouch anal anastomosis is relatively high probably due to steroid given prior to surgery or direct effect of anorectal mucosal inflammation. Regards to postoperative bowel function, nocternal soiling is frequently recognized in the patients who received this operation. To overcome these technical and functional disadvantages, anal transitional zone preservation without mucosectomy and stapled anastomosis between pouch and the upper rim of the puborectalis muscle has been performed. Our series of 84 cases with this modified method, anastomotic leakage was significantly decreased and nocternal soiling was completely disappeared within 7 months postoperatively. And one stage procedure became possible unless severe, or high doses of steroid given prior to surgery. Only one case of mild dysplasia was experienced in the remaining rectal mucosa which was disappeared at the next examination. Medical treatment to the remaining lesion was not necessary in the most of cases. Anal canal preservation is superior to mucosectomy in the points of bowel function and minimizing postoperative complications.

Anal Canal

[Clinical study of occupational uroepithelial cancer].

We studied 438 persons who were engaged in the production and use of aromatic amines (benzidine sulfate, beta-naphthylamine, alpha-naphthylamine and dianisidine). Among these 438 persons, 88 new cases of occupational uroepithelial cancer had occurred from 1949 to 1995. The incident rate of occupational uroepithelial cancer was 20.1%. The average exposure period of these 88 cases to the aromatic amines was 7.40 years (range, 0.75-26.75), and the incidence rate of tumors increased with the length of exposure to aromatic amines. The average latent period was 26.79 years (range, 1.33-48.50), and the average age of first onset was 52.59 (range, 24-79). Recently it has been determined that the longer the latent period, the older the age of first onset. Of these 88 cases, the tumor sites were bladder in 67 cases (76.1%) and upper urinary tract (renal pelvis and/or ureter) in 5 cases (5.7%). The other 16 cases (18.2%) were the bladder and upper urinary tract. The screening examination for chemical workers using urinary cytology was begun in 1962. In our cases, urine cytology was a useful method for diagnosing occupational uroepithelial cancer. As for initial treatment of the 88 cases, transurethral surgery was most frequently performed, that is on 58 cases (65.9%). However, eight cases (9.1%) had to undergo a total nephroureterectomy, and six cases (6.8%) had a total cystectomy. Recurrence was observed in 61 cases (69.3%) out of the 88 patients with an average of 1.81 times. The other organic cancers developed in 39 cases (8.9%) out of 438 workers who were exposed to aromatic amines and in 8 cases out of 88 patients (9.1%). Prognosis of the 88 patients is that, the number of alive and dead is 51 (58.0%) and 37 (42.0%) respectively on December 31, 1995. Twenty-eight patients (31.8%) died of uroepithelial cancer, and five patients (5.7%) died of other organic cancers. The survival rates of 5, 10, 15 and 20 years was 87.9%, 74.0%, 65.9% and 56.3%, respectively. From these results, patients with occupational uroepithelial cancer and workers who are exposed to aromatic amines should undergo long term observation.

2-Naphthylamine

Incidence of p53 and Ha-ras gene mutations in chemically induced rat mammary carcinomas.

To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha-ras genes were examined for mutations by polymerase chain reaction single-strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA-induced mammary tumors had a p53 mutation, a single-base substitution (AGC-->GGC) at codon 307, resulting in an amino-acid change from Ser to Gly. No mutations were found in NMU-induced tumors. The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha-ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors.

9,10-Dimethyl-1,2-benzanthracene

Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate.

The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and the subsequent formation of a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in the rat kidney (Umemura et al., 1990). Using an improved DNA isolation method (Nakae et al., 1995), which reduces the background level of 8-OH-Gua, we found a five-fold increase in the 8-OH-Gua level in kidney DNA after a single i.p. injection of Fe-NTA. On the basis of the report that 8-OH-Gua repair activity is enhanced after cells are exposed to oxidative stress due to ionizing radiation (Bases et al., 1992), the measurement of 8-OH-Gua repair activity will also be useful to assess cellular oxidative stress. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22 mer DNA that contains 8-OH-Gua at a specific position. A five-fold increase in the 8-OH-Gua repair activity as compared with the control, was observed in the target organ, the rat kidney, 120 h after Fe-NTA administration. In the non-target organ, the liver, the increase was not as large (two-fold). This simple assay of oxidative DNA damage repair will be useful for evaluating the carcinogenicity of oxygen radical forming chemicals, in addition to chemical analyses of oxidative DNA damage.

Animals

Centration and fixation of posterior chamber intraocular lenses in eyes with pseudoexfoliation syndrome. An analysis of explanted autopsy eyes.

Pseudoexfoliation syndrome is an important risk factor in cataract surgery. We examined decentration of posterior chamber intraocular lenses in a series of 24 autopsy eyes with pseudoexfoliation syndrome that had undergone cataract surgery and intraocular lens implantation. The results were compared to a control group of 25 normal autopsy eyes that matched the pseudoexfoliation collection for age distribution, implant duration and further anatomical parameters. The mean lens decentration in all pseudoexfoliation eyes (0.75 +/- 0.38 mm) was significantly higher than in the control group (0.40 +/- 0.29 mm) (p = 0.0008). Analysis of subgroups with symmetrical bag/bag fixated intraocular lenses showed a significantly higher decentration in the pseudoexfoliation group (p = 0.04). The main reason for decentration was a decentration of the entire capsular bag in pseudoexfoliative eyes (p = 0.001), which was related to zonular weakness and damage. The results indicate that in patients with pseudoexfoliation syndrome alternative fixation sites, like sulcus or transscleral fixation, should also be considered.

Aged

[MRSA enteritis following severe gastroenteritis of salmonellosis].

A 62-year-old female patient was given cancer chemotherapy for lymph nodes metastases in the left breast cancer. She was admitted to the hospital because of severe watery diarrhea, in hypovolemic shock, and was diagnosed as suffering from not-typhoidal Salmonella by stool culture. After systemic administration of antibiotic agents, she became well in a few days, but on the 16th hospital day, she had severe watery diarrhea, hypovolemic shock and then cardiac arrest. She was resuscitated immediately. The stool culture revealed methicillin-resistant Staphylococcus aureus (MRSA), type II coagulase, producing TSST-1 and type BC staphylococcal enterotoxin. It was thought that in this case, MRSA enteritis was caused by damage of the intestinal mucosal barrier of the defense mechanism against infection due to salmonellosis and administration of multiple antibiotic agents.

Anti-Bacterial Agents

Increase in the 8-hydroxyguanine repair activity in the rat kidney after the administration of a renal carcinogen, ferric nitrilotriacetate.

One type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), is known to increase in rat kidney DNA after the administration of a renal carcinogen, ferric nitrilotriacetate (Fe-NTA). To determine the involvement of oxygen radicals in Fe-NTA carcinogenesis, we examined whether the 8-OH-Gua repair enzymes are induced in the rat kidney after Fe-NTA administration, in addition to our analysis of the 8-OH-Gua levels in the DNA, because the 8-OH-Gua repair activity is known to be induced in mammalian cells by oxidative stress due to ionizing radiation. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22-mer double strand DNA, which contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua repair activity was observed in the rat kidney after a single intraperitoneal injection of Fe-NTA (p < 0.01). This is the first report on the induction of the repair activity for 8-OH-Gua after treatment with a chemical carcinogen. This assay will be useful for evaluating the carcinogenicity of oxygen radical-forming chemicals.

Animals

Role of protein phosphatase in malignant osteogenic and soft tissue tumors.

The expression of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in osteogenic tumors and soft tissue tumors by immunohistochemical analysis. The percentage of cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1, was significantly higher in malignant osteogenic tumors (chondrosarcoma, osteosarcoma, and Ewing's sarcoma) and in malignant soft tissue tumors (liposarcoma and malignant fibrous histiocytoma [M.F.H.]) than in benign tumors (osteochondroma, osteoblastoma, ossifying fibroma, enchondroma and lipoma). Furthermore, the malignant tumor lesions showed a markedly high number of cells in the S-phase fraction of the cell cycle, as compared to benign tumors. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant tumor cells.

Bone Neoplasms

[The histological changes in the spinal cord following percutaneous cervical cordotomy (PCC) and correlation of these changes with the efficacy of PCC].

We observed the histological changes in the spinal cord following percutaneous cervical cordotomy (PCC) and correlation of these changes with the efficacy of PCC in 7 cases. A fine monopolar electrode which we used, measured 0.25 mm or 0.27 mm in diameter with exposed length of 2 mm. An oval or elliptical-shaped lesion, 1 to 3 mm in width and 3 to 4 mm in length, was observed in 6 of these cases. The main lesion was found in the anterolateral column in 5 cases. In 3 of these 5 cases, the whole anterolateral column had been destroyed, and in the other 2 cases dorsal one half to two thirds of it had been destroyed. In these 5 cases, pain sensation on the opposite side of PCC was lost for a long time and pain was relieved until death (21-239 days after PCC). In the other 2 cases the lesion in the anterolateral column was tenuous or unrecognizable, and the loss of pain sensation was temporary with pain recurring by the next day. This study showed that an oval or elliptical-shaped lesion was made in PCC and that in cases in which main lesion was located in the anterolateral column, pain relief was long lasting.

Adult

Seton treatment for perianal Crohn's fistulas.

In this study, we evaluated the efficacy of long-term seton drainage in the management of 13 patients with severe perianal Crohn's fistulas which had proven to be intractable to conventional therapy. After adequate curettage of the fistulous tracts and infected tissue, either a Penrose drain or a fine polyethylene catheter was inserted to encircle the tracts and tied. Patients were followed up for a mean period of 12.1 months. Perianal pain disappeared or improved in all 13 patients, while the body temperature of all 7 with pyrexia dropped to within the normal range. Discharge disappeared or diminished in 77% (10/13) and tenderness disappeared or improved in 77% (10/13). Induration disappeared or improved in 69% (9/13). Overall, good results were achieved in 10 patients, although 3 required redrainage. In one of these patients, a good result was achieved after colostomy was performed for active intestinal disease. Nevertheless, 2 patients did not improve, one of whom required lay-open surgery after seton treatment. In 8 of the 13 patients, some seton drains were able to be removed, and none of the patients experienced any soiling or leakage. Thus, we conclude that seton treatment is worthwhile in the management of perianal Crohn's fistulas as it alleviates the symptoms and simplifies multiple tracts. Moreover, it preserves sphincter function, is less invasive, and can be managed easily.

Adult

Cytochrome P4501A1 gene polymorphism and homozygous deletion of the glutathione S-transferase M1 gene in urothelial cancer patients.

Japanese urothelial (bladder, renal pelvis and ureter) cancer patients (n = 83) and community controls (n = 101) were compared for rates of polymorphism in exon 7 of the cytochrome P4501A1 (CYP1A1) gene or homozygous deletion of the glutathione S-transferase class mu (GSTM1) gene. A CYP1A1 polymorphism was detected in a HinCII polymorphism assay utilizing a primer with a single base pair mismatch. The frequency distribution of the CYP1A1 genotypes in urothelial cancer patients showed no significant difference from that in healthy controls. The increased frequency of homozygous deletions of GSTM1 gene loci in patients with urothelial cancer was statistically significant compared with the controls, 51 of 83 (61%) and 43 of 101 (43%) (odds ratio = .2.15, 95% confidence interval = 1.18-3.86). These results lead us to conclude that homozygous deletion of the GSTM1 gene may be associated with susceptibility to urothelial cancer.

Adult

Observations on the growth rate of renal cell carcinoma.

We retrospectively reviewed the records of 18 patients to investigate the growth rate of renal cell carcinoma (RCC). Growth rates were calculated from two or more gross measurements of neoplastic foci in the kidney (6 cases) and lung (12 cases). RCCs in primary sites grew slowly and the tumor volume doubling time (DT) raged from 372 to 579 days (468 +/- 84.6). Pulmonary metastases present in 12 cases grew rapidly, with a DT ranging from 20 to 154 days (89.4 +/- 43.0). Tumors in both the kidney and lung were composed of cancer cells with equal proliferative activity, as determined by immunohistochemical analysis of argyrophilic nucleolar organizer regions and proliferating cell nuclear antigen activity. Thus, our results suggest that, in addition to the proliferative activity of cancer cells, the microenvironment of the specific region is an important determinant of the growth rate of cancer cells.

Adult

[A survey of the inclinations of medical students towards becoming occupational physicians].

We conducted a survey to investigate medical students awareness of the activities of occupational physicians and their willingness to do postgraduate courses in this field. Those surveyed were fifth grade students in six universities in the Kinki district of Japan in 1993. In analyzing the responses of 368 eligible subjects, the response rate was 68.4% and the following results were obtained. 1) Only one of the 368 subjects expressed a desire to become an occupational physician after graduation, however 24.2% of those surveyed had considered becoming occupational physicians. More female students and, males over the age of 25, had considered becoming occupational physicians. Anxiety about a possible surplus of medical doctors in the near future was a factor that led them to consider becoming occupational physicians. 2) There were few negative responses concerning the activities of occupational physicians, even among those who had not considered becoming occupational physicians. 88.3% of those surveyed complained of a lack of information regarding postgraduate courses. 3) Responses were varied concerning conditions in the practice of occupational physicians. Those who had considered becoming occupational physicians were mostly concerned with the establishment of a system for the acceptance of occupational physicians in industry, while those who had not thought of becoming occupational physicians, considered practicing as occupational physicians as a sideline to regular clinic duties. 4) Having considered the above results and those of other researchers, we concluded that supplying more information related to the activities of occupational physicians and offering further postgraduate training programs in occupational medicine would encourage more medical students to become occupational physicians.

Career Choice