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Biomedical subjects

T Sawai

Publications and source records attributed to T Sawai.

At least 109 records · Page 6Linked to original sources
PubMed1999

Structure of the extended-spectrum class C beta-lactamase of Enterobacter cloacae GC1, a natural mutant with a tandem tripeptide insertion.

A class C beta-lactamase from a clinical isolate of Enterobacter cloacae strain GC1 with improved hydrolytic activity for oxyimino beta-lactam antibiotics has been analyzed by X-ray crystallography to 1.8 A resolution. Relative to the wild-type P99 beta-lactamase, this natural mutant contains a highly unique tandem repeat Ala211-Val212-Arg213 [Nugaka et al. (1995) J. Biol. Chem. 270, 5729-5735]. The 39.4 kDa chromosomal beta-lactamase crystallizes from poly(ethylene glycol) 8000 in potassium phosphate in space group P2(1)2(1)2 with cell dimensions a = 78.0 A, b = 69.5 A, and c = 63.1 A. The crystal structure was solved by the molecular replacement method, and the model has been refined to an R-factor of 0.20 for all nonzero data from 8 to 1.8 A. Deviations of model bonds and angles from ideal values are 0.008 A and 1.4 degrees, respectively. Overlay of alpha-carbon atoms in the GC1 and P99 beta-lactamases results in an rms deviation of 0.6 A. Largest deviations occur in a loop containing Gln120 and in the Omega loop region (200-218) where the three residues 213-215 are disordered. Possibly as a result of this disorder, the width of the opening to the substrate binding cavity, as measured from the 318-324 beta-strand to two loops containing Gln120 and Tyr150 on the other side, is 0.6-1.4 A wider than in P99. It is suggested that conformational flexibility in the expanded Omega loop, and its influence on adjacent protein structure, may facilitate hydrolysis of oxyimino beta-lactams by making the acyl intermediate more open to attack by water. Nevertheless, backbone atoms in core catalytic site residues Ser64, Lys67, Tyr150, Asn152, Lys318, and Ser321 deviate only 0.4 A (rmsd) from atoms in P99. A rotation of a potential catalytic base, Tyr150, relative to P99 at pH 8, is consistent with the requirement for a lower than normal pK(a) for this residue.

Amino Acid Sequence↗
PubMed1999

Structure and expression of an adhesive protein-like molecule of mosquito invasive-stage malarial parasite.

Invasion of the malarial parasite into a vector mosquito begins when the motile ookinete transverses the gut epithelium. Adhesive proteins that may mediate this invasive process have not been identified to date. We found that a molecule with an adhesive protein-like structure was expressed in the ookinete of Plasmodium berghei. This protein is structurally homologous to circumsporozoite protein and thrombospondin-related adhesive protein (TRAP)-related protein, CTRP, of Plasmodium falciparum. We named it P. berghei CTRP (PbCTRP) and report here its structure and manner of expression. PbCTRP has six integrin I region-like domains and seven thrombospondin-like domains in its putative extracellular region. This structure is similar to that of CTRP and TRAPs of malaria sporozoite. The putative transmembrane and cytoplasmic regions of PbCTRP, CTRP, and TRAP also have conserved amino acid sequences. PbCTRP is produced at least 10 h after fertilization when zygotes begin transformation to ookinetes. In the mature ookinete, PbCTRP is located mainly in the anterior cytoplasm. The staining pattern was also similar to TRAP in the sporozoite. We suggest that PbCTRP may play a role in ookinete invasive motility and belongs to a protein family together with TRAP and other structurally related proteins of apicomplexan parasites.

Amino Acid Sequence↗
PubMed1999

Relationship between hyaluronan production and metastatic potential of mouse mammary carcinoma cells.

To investigate the roles of hyaluronan produced by cancer cells in cancer metastasis, the metastatic potential of the highly metastatic mouse mammary carcinoma FM3A HA1 cell line was compared with those of hyaluronan-deficient mutant cells. Five different mutant clones showed markedly reduced hyaluronan production and lacked the ability to form hyaluronan-rich pericellular coats. These mutant clones displayed significant decreases in metastatic ability compared with the parental cells after i.v. injection into syngeneic mice. These results suggested that the decreased hyaluronan production caused not only the lack of matrix formation but also decreased metastatic potential of the cancer cells. Expression of mouse hyaluronan synthase 1 (HAS1) by transfection into HAS- cells defective in hyaluronan synthase activity rescued hyaluronan matrix formation as well as hyaluronan production. Lung metastasis after i.v. injection of HAS1 transfectants was also recovered significantly. The results provide direct evidence for the involvement of hyaluronan in cancer metastasis.

Animals↗
PubMed1999

Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation.

Graft recurrence of insulin-dependent diabetes mellitus (IDDM) was examined. Islet transplantation or pancreas-alone transplantation excluding the duodenum and peripancreatic lymph nodes was compared with whole pancreaticoduodenal transplantation. A Wistar Furth (WF; RT1(u), RT6.2) to major histocompatibility complex (MHC)-compatible diabetes-prone (DP; RT1(u), RT6.1 gene carrier)-biobreeding (BB) rat transplantation model was used. Only DP recipients that had been transplanted with whole pancreaticoduodenal grafts were free from IDDM recurrence (>60 days postgrafting) when treated with anti-intercellular adhesion moluecule-1 (ICAM)-1/leukocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs). In the spleen cells of the DP rats that had accepted pancreatic grafts (60 days postgrafting), flow cytometric analysis showed that NKR-P1(+)TCRalphabeta(+) (NKT) cells had proliferated markedly, with the proportion of 12.8 +/- 1.7% in the total splenic T cells, most of which (86.2%) were derived from the donor (RT6.2(+)). By enzyme-linked immunonosorbent assay (ELISA), serum interferon gamma (IFN-gamma) was not detected (<13 pg/ml) in all rats. However, interleukin-4 (IL-4) was detected as 158.8 +/- 28.0 pg/ml in the nonrecurrent DP recipients. These data suggested that to prevent IDDM recurrence in the pancreatic graft, the lymphocytes in the pancreaticoduodenal grafts are necessary. Also, the donor-derived NKT cells might have some immunoregulatory functions with a Th2 deviation.

Animals↗
PubMed1999

Successful transvaginal repair of a rectovaginal fistula developing after double-stapled anastomosis in low anterior resection: report of four cases.

The management of postoperative rectovaginal fistula (RVF) after low anterior resection for rectal cancer is difficult and the results are often unsatisfactory. Among 140 patients with rectal cancer who underwent low anterior resection with a double-stapled anastomosis at our hospital between 1986 and 1996, 4 (2.9%) developed RVF as a postoperative complication. The RVF developed gradually from 9 to 128 days after low anterior resection. We describe herein our technique of using a modified transvaginal approach for RVF repair with a diverting colostomy. In all four patients, the RVFs were completely eradicated with reestablishment of intestinal continuity and did not recur during the mean follow-up period of 29.5 months, ranging from 12 to 67 months. This report serves to demonstrate that emerging RVFs secondary to stapled anastomosis in low anterior resection for rectal cancer must be recognized, and that a modified transvaginal approach provides an effective method of repair.

Adolescent↗
PubMed1999

The use of an omental pedicle graft to prevent small-bowel obstruction after restorative proctocolectomy.

Small-bowel obstruction remains one of the most frequent complications after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Of particular concern is small-bowel adhesion to the pelvic dead space that causes afferent limb obstruction, sometimes necessitating laparotomy. In this report, we describe a technique using an omental pedicle graft (OPG) to fill the pelvic dead space to prevent small-bowel obstruction and the resulting afferent limb obstruction after IPAA. The OPG is created from the left half of the omentum, while maintaining the blood supply from the left gastroepiploic vessels. The omentum is placed into the pelvis along the left paracolic gutter from where the colon has been resected. It is then passed over the pelvic brim and placed behind and along the bilateral sides of the ileal pouch, filling the space. This modified technique was employed in the treatment of four patients with chronic ulcerative colitis, none of whom developed any signs of small-bowel obstruction.

Chronic Disease↗
PubMed1999

Relationship between Ca-dependent change of serum PTH and extracellular Ca2+-sensing receptor expression in parathyroid adenoma.

Abnormal PTH secretion and cell growth in hyperparathyroid tissues are accompanied with reduced expression of Ca2+-sensing receptor (CaR) which plays a key role in Ca-regulated PTH release. In this study, we examined the receptor expression in parathyroid adenomas using specific anti-CaR antibody and investigated relationship between CaR expression in adenomatous tissues and parameters of Ca-dependent change of serum PTH. The results show a considerable variation in the number of CaR positive cells among the adenomatous tissues. Expression of the receptor protein was not related to set-point error but was more reduced in the patients with more elevated minimum or baseline levels of serum PTH. CaR expression was severely reduced in the patients with highly elevated maximum serum PTH, while the receptor expression was also decreased in some patients with normal maximum serum PTH. Baseline level / maximum level ratio of serum PTH was increased in these patients. In conclusion, reduced CaR expression is related to abnormality in three parameters of PTH secretion (minimum serum PTH, maximum serum PTH, and baseline level / maximum level ratio of serum PTH) and may contribute to hypersecretion from parathyroid adenomas.

Adenoma↗
PubMed1999

Clinical significance of the lung/thorax transverse-area ratio in fetuses with cystic lung disease.

We examined the clinical significance of the lung-thorax transverse-area ratio (L/T) in fetuses with cystic lung disease (CLD). The transverse section of the thorax was analyzed at the level of the 4-chamber view of the heart. L/T was calculated as the bilateral normal lung area divided by the thoracic area. Within a 9-year period, ultrasonography was performed in 15 fetuses with CLD, 13 of which were histologically diagnosed: congenital cystic adenomatoid malformation of the lung (CAM; n = 8), pulmonary sequestration (n = 4), and bronchial atresia (n = 1). Although the initial L/T measurement (29.6 +/- 4.2 weeks) showed significantly lower values than in the controls, the final measurement (36.4 +/- 1. 6 weeks) indicated that the L/T in CLD excluding CAM was significantly higher than that in CAM. Six patients with a final L/T of less than 0.21 required mechanical ventilation immediately after birth. Two of these patients died, and the autopsy findings indicated pulmonary hypoplasia. In these cases, a significant correlation was observed between the maximal value of L/T and preductal alveolar-arterial oxygen difference (A-aDO(2)), although the final L/T was not correlated to A-aDO(2). These results indicate that serial measurements of L/T may be useful in the diagnosis of CLD and may help to predict postnatal respiratory conditions.

Bronchopulmonary Sequestration↗
PubMed1999

High serum concentrations of sialyl Tn antigen in carcinomas of the biliary tract and pancreas.

Sialyl-Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. In the present study, we compared the serum level of STn antigen in 14 patients with benign diseases of the biliary tract and pancreas, 15 patients with bile duct cancers, and 9 patients with cancer of the pancreas. High levels of serum STn (>45 U/ml) were frequently detected in patients with carcinoma of the biliary tract (53.3%) or pancreas (55.6%), compared with the detection of high levels in those with benign diseases (14.3%; P < 0.05). Serum levels of STn did not correlate with the presence of jaundice, cholangitis, or pancreatitis, or with the level of carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9. In cancer tissues, the expression of STn antigen detected by immunostaining correlated significantly with serum STn (P < 0.05). Our results indicate that measurement of serum STn level may be potentially useful for the diagnosis of carcinomas of the biliary tract and pancreas, particularly when combined with other tumor markers such as CEA or CA19-9.

Adult↗
PubMed1999

Expression of multidrug resistance protein in metastatic colorectal carcinomas.

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.

ATP-Binding Cassette Transporters↗