Search PubMed⌕ Search

Biomedical subjects

K Sawai

Publications and source records attributed to K Sawai.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cell-specific targeting of a thymidine kinase/ganciclovir gene therapy system using a recombinant Sindbis virus vector.

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. The possibility of using a novel targetable Sindbis virus expression vector containing the HSV-TK gene was examined. Baby hamster kidney (BHK) cells and several human tumor cells infected with a Sindbis virus containing the HSV-TK gene showed strong expression of HSV-TK protein. Cells transduced with the HSV-TK gene exhibited increased TK activity, ranging from 3- to 20-fold over an average baseline level. The human HeLa-CD4+ cells infected with recombinant Sindbis virus containing the HSV-TK gene were sensitive to low concentrations of GCV (0.1-1 microg/ml) and the 50% growth inhibitory concentration (IC50) was 0.6 microg/ml. We also demonstrated applications of cell type-specific Sindbis virus-mediated antigen-antibody targeting of the HSV-TK/GCV system in vitro. Sindbis virus containing the HSV-TK gene packaged in a helper virus displaying the IgG-binding domain of protein A on its envelope could infect various tumor cell lines in the presence of specific antibodies that recognize antigens on their surfaces. HSV-TK-transduced tumor cell lines exhibited sensitivity to GCV. Our data suggest the potential for targeted gene therapy of the HSV-TK/GCV system using a cell type-specific recombinant Sindbis virus vector-antibody system.

Animals↗
PubMed1999

Reducing cytotoxicity induced by Sindbis viral vectors.

Sindbis virus has been recognized as a potentially useful virus vector for gene therapy. In an effort to improve its utility and provide cell-targeting capability to gene therapy vectors, we recently developed Sindbis virus vectors possessing chimeric envelopes with cell-specific targeting ability [K. Ohno et al. Nature Biotechnol 15:763-767, 1997; K. Sawai et al. Biochem Biophys Res Commun 248:315-323, 1998]. However, a residual problem associated with Sindbis virus vectors is the apoptotic effect of this virus on infected cells. To address this issue, we have studied the possible role of bcl-2 expression. Bcl-2 expression has been postulated to facilitate the establishment of persistent Sindbis viral infection by blocking virus-induced apoptosis. In this study we produced a Sindbis virus vector capable of expressing human bcl-2 and the reporter gene, lacZ. This chimeric virus (SinRep/lacZ/bcl-2/DH-BB) showed a marked reduction in induced apoptosis in infected cells. For example, after infection with this vector, cell proliferation of BHK cells was 55% of that of uninfected cells 2 days after infection and 40% 3 days after infection. While this reflected a significant degree of apoptosis, the effect was much less pronounced than that seen with wild-type Sindbis virus. Cell proliferation was reduced to 26% 2 days after wild-type virus infection of BHK cells and to only 7% 3 days after infection. Although additional work will be required to eliminate apoptosis induced by Sindbis virus vectors, the studies reported here suggest that such a goal may be achievable after additional modification of the vectors.

Animals↗
PubMed1999

Total gastrectomy with simultaneous pancreaticosplenectomy or splenectomy in patients with advanced gastric carcinoma.

A splenectomy or distal pancreaticosplenectomy is often performed simultaneously with total gastrectomy in the treatment of gastric carcinoma to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. However, the negative impact of splenectomy and pancreaticosplenectomy has also been reported. A retrospective analysis was performed to evaluate the outcomes of distal pancreaticosplenectomy and total gastrectomy, splenectomy and total gastrectomy, and gastrectomy alone in the patients with advanced gastric carcinoma without distant metastasis. Prognostic factors were examined. No significant differences existed in 5-year survival in the patients who underwent gastrectomy with splenectomy, gastrectomy with distal pancreaticosplenectomy, or gastrectomy alone. Neither splenectomy, nor distal pancreaticosplenectomy were prognostic factors. However, distal pancreaticosplenectomy was an independent predictor of pancreatic fistula. In conclusion, the addition of distal pancreaticosplenectomy or splenectomy to total gastrectomy for gastric cancer increases the risk of severe complications, but does not improve survival.

Aged↗
PubMed1999

No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer.

BACKGROUND: It remains unknown whether extended surgery improves the survival rate of patients with gastric cancer. This study was a review of combined pancreaticosplenectomy with total gastrectomy for gastric cancer. METHODS: The clinicopathological details of 190 patients who underwent combined pancreaticosplenectomy with total gastrectomy between 1969 and 1996 were compared retrospectively with those of 206 patients who underwent total gastrectomy with splenectomy alone. RESULTS: There was no statistical difference in the survival rate when pancreaticosplenectomy was added to total gastrectomy. The mortality rate was similar, but the morbidity rate was higher in patients who had pancreaticosplenectomy. Six patients who had direct pancreatic invasion and two thought to have involved lymph nodes along the splenic artery survived for more than 5 years after operation. In the latter group, the metastatic lymph nodes along the splenic artery could have been resected without pancreatectomy. CONCLUSION: Since a combined pancreaticosplenectomy adds no survival advantage to total gastrectomy for gastric cancer, this procedure should no longer be regarded as routine.

Female↗
PubMed1999

Number and anatomical extent of lymph node metastases in gastric cancer: analysis using intra-lymph node injection of activated carbon particles (CH40).

BACKGROUND: The long-term survival of 200 patients with gastric cancer who underwent radical gastrectomy was analyzed with respect to the number and anatomical extent of lymph node metastasis. All of the patients received intra-lymph node injection of fine activated carbon particle solution (CH40) during surgery. METHODS: The average number of resected lymph nodes increased in line with the anatomical level of lymph node dissection; 32.5 per patient in D1, 42.3 in D2, 3 and 66.3 in D4. The percentage of blackened lymph nodes without metastasis (42.4%) was slightly higher than that of lymph nodes containing metastasis (37.2%), but the difference was not statistically significant. Of the 200 patients, 61 (30.5%) had microscopic evidence of metastatic lymph node involvement. Twenty-two patients had between one and three metastatic lymph nodes, 19 had between four and nine and 20 patients had more than nine. The 5-year survival rate was 93.1% in patients without lymph node metastasis, 71.9% in patients with 1-8 metastatic nodes, 36.1% in patients with 4-9 nodes and 19.2% in patients with > 9 nodes. RESULTS: The 5-year survival rate according to the anatomical extent of metastatic lymph nodes was 93.1% in n0, 63.1% in n1, 37.9% in n2, 27.8% in n3 and 0% in n4. The number of metastatic lymph nodes and also their anatomical extent were identified as independent prognostic factors for survival by multivariate analysis. CONCLUSION: The number and anatomical extent of metastatic lymph nodes have similar impacts on prognosis in gastric cancer.

Adult↗
PubMed1999

Regional lymph node metastasis as a predictor of peritoneal carcinomatosis in patients with Borrmann type IV gastric carcinoma.

OBJECTIVE: Postoperative survival of patients with Borrmann type IV gastric carcinoma is significantly worse than that in patients with other Borrmann types of gastric carcinomas. The most common pattern of recurrence in patients with Borrmann type IV gastric carcinoma is peritoneal metastasis. We examined the predictors of developing peritoneal metastasis. METHODS: We retrospectively analyzed the relationship between peritoneal metastasis and Borrmann type IV gastric carcinoma. We also examined the dependence of the peritoneal metastasis on clinicopathological findings. RESULTS: Borrmann type IV was an independent prognostic factor of survival by multivariate analysis, and regional lymph node metastasis was an independent predictor of peritoneal metastasis in patients with Borrmann type IV gastric carcinoma. CONCLUSION: Because type of lymph node dissection was not associated with developing peritoneal metastasis, early detection of cancer without lymph node metastasis may be the only means of improving survival in patients with Borrmann type IV gastric cancer.

Carcinoma↗
PubMed1999

[Development of cancer treatment practice guidelines in Japan: advantages and disadvantages].

The development of clinical practice guidelines for the systematic treatment of cancer is being promoted as a way to assist clinicians and patients. In this paper, the advantages and disadvantages of developing clinical practice guidelines for both clinicians and patients are discussed. Physicians may regard guidelines to be unrealistic, and some may even consider guidelines to be a challenge to their autonomy. However, the advantages of guidelines for the patients and clinicians exceed any disadvantages. The development of guidelines should therefore be promoted, although with consideration of both the many advantages and disadvantages for clinicians and patients.

Diagnosis-Related Groups↗
PubMed1999

[Treatment of postoperative recurrence of digestive cancers: peritonitis carcinomatosa].

Carcinomatous peritonitis is the most frequent type of recurrence observed after surgery for cancer of the digestive tract. Most patients with carcinomatous peritonitis present with bowel obstruction and/or ascites. Surgical treatment including colostomy and intestinal anastomosis and chemotherapy have been attempted in patients with carcinomatous peritonitis, although the results have not been satisfactory. New drug delivery systems, such as mitomycin C-adsorbed charcoal, anticancer drugs entrapped in microspheres, and immunoconjugates composed of anticancer drugs and antibodies, will be powerful new tools for the treatment of metastatic cancer.

Digestive System Neoplasms↗
PubMed1999

Concealed hypothyroidism in patients with myeloperoxidase antineutrophili cytoplasmic autoantibodies- (MPO-ANCA) positive renal disease.

AIM: To elucidate the relationship between thyroid disorders and myeloperoxidase (MPO) antineutrophili cytoplasmic autoantibodies-(ANCA) positive renal disease, we investigated the prevalence of thyroid diseases in patients with them. SUBJECTS AND METHODS: The subjects consisted of 10 patients (6 males and 4 females) diagnosed as having MPO-ANCA-positive renal disease in our hospital. To evaluate thyroid function, serum thyroid-stimulating hormone (TSH) and free-thyroxine (FT4) levels were measured by a immunoradiometric assay (IRMA) and a radioimmunoassay (RIA), respectively. Thyroid autoantibodies against microsomal antigen and thyroglobulin were measured by means of particle agglutination. In addition, antibodies against thyroid peroxidase (TPO-Ab) and purified thyroglobulin (Tg-Ab) were also determined by RIA. To assess the disease activity, we employed Birmingham Vasculitis Activity Score (BVAS). RESULTS: The results were that 4 out of 10 patients (40%) were accompanied by hypothyroidism, including 2 patients with subclinical hypothyroidism and I during thyroid hormone replacement therapy. The BVAS of the hypothyroidism group (group A) was significantly lower (p < 0.05) than that of non-hypothyroidism group (group B), 18.5 +/- 9.0 (mean +/- SD) versus 24.2 +/- 16.6. MPO-ANCA titers were not significant between the two groups, 376.8 +/- 316.8 EU versus 311.5 +/- 203.6 EU. CONCLUSION: Thyroid disorder, especially hypothyroidism would not be a rare complication in patients with MPO-ANCA-positive renal disease. We should concentrate more on thyroid lesion in them.

Aged↗
PubMed1999

[Recent spread of home parenteral nutrition in Japan--the view of an HPN managing company].

Terumo Corporation has developed a nation wide home healthcare management system "Home-Joint," which helps hospitals to safely discharge patients early. Recently, this system mainly has been adopted with HPN (home parenteral nutrition) patients. This report evaluates 472 HPN patients who underwent the "Home-Joint" program in 1998, and also presents some issues from the standpoint of a HPN managing company. I. Profiles of HPN patients Number: 472 (female 43%, male 57%) Age: 1-104 (47% patients over 70) DIAGNOSIS: cancer 54%, others 25%, unknown 21% Infusion devices: ambulatory pump 85%, stationary pump 15%, gravity none. Therapeutic periods: average 65.6 days (1-437) for 300 patients who completed the program. II. HPN trends from 1997 to 1998 1. Increase in patients directly supported by hospitals. 2. Wider patient variation: increase in patients under 70 years old, in non-cancer patients and in longer periods (longer than 2 months). III. Issues 1. Development of hospital-clinic-pharmacy local relationship. 2. Development of devices for easier infusion control. 3. Evaluation of HPN outcome for patients' QOL and for cost-effectiveness. HPN is becoming a popular home healthcare therapy in Japan, and it requires higher level of performance by medical staff and managing companies.

Cooperative Behavior↗
PubMed1998

Cell-specific transfection of choriocarcinoma cells by using Sindbis virus hCG expressing chimeric vector.

The development of Sindbis virus vectors that can target specific cell types would provide an important gene therapy strategy. We explored the possibility of designing a Sindbis virus vector that can target human choriocarcinoma cells via ligand-receptor interaction. The Sindbis virus envelope gene was modified by insertion of the alpha- and beta-hCG genes. The chimeric helper RNA was then transfected into BHK cells along with a virus-based expression vector, allowing the production of virus particles containing hCG-envelope chimeras. The hCG-envelope chimeric virus vector has minimal infectivities against BHK cells and human cancer cells which do not contain LH/CG receptors on their surface. This vector can, however, infect and transfer a reporter gene to choriocarcinoma cells as well as other cells bearing LH/CG receptors. This chimeric Sindbis virus vector may provide a novel approach for gene therapy of gestational trophoblast disease and placental dysfunction.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Recent advances in surgical treatment have improved the survival of patients with gastric carcinoma.

BACKGROUND: Mortality resulting from gastric carcinoma is decreasing. This is mainly due to vigorous endoscopic screening and the consequent higher incidence of early detection of the disease. In this study, to evaluate the effect of surgical treatment on the prognoses of patients with gastric carcinoma, the survival of 1579 patients who underwent gastrectomy between 1970 and 1994 was retrospectively analyzed. METHODS: The patients were divided into 5 groups at 5-year intervals. Postoperative survival was compared among the groups. RESULTS: Postoperative survival was significantly improved in the later groups for patients with Stage I, II, III, and IV disease. A multivariate analysis of prognostic factors revealed that the time period during which the gastrectomy was performed was an independent predictor of survival. CONCLUSIONS: It was concluded that survival has been improved by recent advances in the surgical approach to gastric carcinoma.

Carcinoma↗
PubMed1998

Characterization of signet ring cell carcinoma of the stomach.

BACKGROUND AND OBJECTIVES: As there is no consensus regarding the prognosis of patients with signet cell carcinoma of the stomach compared with other types of gastric cancer, we retrospectively studied the clinicopathologic features and prognosis of signet cell carcinoma in comparison with other types of gastric cancer. METHODS: Gastrectomies were performed because of gastric cancer in 1,498 patients between 1970 and 1994. Of the 154 patients diagnosed with signet ring cell carcinoma, 94 had early and 60 had advanced gastric carcinoma. The percentage of patients with an early carcinoma was significantly higher among those with signet ring cell carcinoma compared with those with other gastric carcinoma histologies. RESULTS: The survival of the total group of patients with signet ring cell carcinoma was significantly better than that of patients with other types of gastric carcinoma (P < 0.05). Survival of the subset of patients with early signet ring cell carcinoma was also improved compared with patients with other types of gastric carcinoma (P < 0.05). However, patients with advanced signet ring cell carcinoma had a poor prognosis similar to that of patients with other types of gastric carcinoma.

Carcinoma, Signet Ring Cell↗
PubMed1998

A novel method of cell-specific mRNA transfection.

In this study, we developed a cell-specific mRNA transfection system using streptavidin-protein A (ST-PA) fusion protein and monoclonal antibodies (mAbs). We previously reported that ST-PA fusion protein and mAb complexes can transfer certain biotinylated proteins into specific cell types. At this time, we combined an in vitro transcribed biotinylated and self-replicating Sindbis virus genomic RNA with ST-PA fusion protein and mAbs. In the presence of cationic liposomes, to prevent RNA degradation, this complex is able to transfect a reporter gene to specific cancer cells in a mAb does-dependent manner. Even in the absence of cationic liposomes, biotinylated mRNA, ST-PA fusion, and mAb complexes can transfer some types of cancer cell suspension cultures. This cell-specific transfection system is a novel method of introducing various mRNAs into cells that results in high levels of transient protein expression.

Animals↗
PubMed1998

Hyperprolactinemic recurrent miscarriage and results of randomized bromocriptine treatment trials.

OBJECTIVE: To evaluate hyperprolactinemia in the pathogenesis of recurrent spontaneous abortion. DESIGN: Randomized trial. SETTING: Miscarriage clinic, Yokohama City University Hospital, Yokohama, Japan. PATIENT(S): From a group of 352 women with recurrent spontaneous abortion, we identified 64 patients with a prolactin disorder that was not associated with any other etiologic abnormalities, including ovarian or endocrinologic disturbances such as luteal phase dysfunction, polycystic ovaries, hypersecretion of LH, galactorrhea, or thyroid hormone disorders. INTERVENTION(S): Restoration of prolactin levels with bromocriptine. MAIN OUTCOME MEASURE(S): Successful pregnancy (live birth). RESULT(S): The percentage of successful pregnancies was higher in the bromocriptine-treated group than in the group that was not treated with bromocriptine (85.7% versus 52.4%, P < .05). Serum prolactin levels during early pregnancy (5-10 weeks of gestation) were significantly higher in patients who miscarried (31.8-55.3 ng/mL) than in patients whose pregnancies were successful (4.6-15.5 ng/mL, P < .01 or P < .05). CONCLUSION(S): Appropriate circulating levels of prolactin may play an important role in maintaining early pregnancy, especially in cases of hyperprolactinemic recurrent miscarriage.

Abortion, Habitual↗
PubMed1998

Mechanical strength of calcium phosphate cement in vivo and in vitro.

Two different kinds of calcium phosphate cement were developed for implant fixation: cement A comprised of alpha-tricalcium phosphate (alpha-TCP) 95% and dicalcium phosphate dihydrate (DCPD) 5%, and cement B comprised of alpha-tricalcium phosphate 90% and dicalcium phosphate dihydrate 10%. The compression strength and pullout force of the new materials were tested both in vitro and in vivo. Microscopic observations were performed on the interface between bone and cement. Cement A showed a greater mechanical strength than cement B. The results suggest the clinical possibility of this calcium phosphate cement, which could be used as a material for enhancing implant fixation.

Animals↗
PubMed1998

Regulation of placental monocyte chemotactic and activating factor during pregnancy and chorioamnionitis.

A number of placental cytokines participate in the feto-maternal defence mechanism. Monocyte chemotactic and activating factor (MCAF) is one of these chemokines. We investigated the pattern of placental MCAF production, the localization of MCAF-producing cells in the placenta, and alterations in its expression in chorioamnionitis. The amounts of MCAF protein produced by the placenta increased during pregnancy irrespective of the presence of uterine contraction. MCAF mRNA was expressed at equivalent levels in the first and second trimester placenta, but at higher levels in the third trimester placenta. Chorioamnionitis in the third trimester placenta induced a 10-fold increase in MCAF protein production and a 3-fold increase in MCAF mRNA level. Immunohistochemical analysis of the placenta revealed the MCAF-producing cells to be trophoblasts. Stimulation of placental cells with lipopolysaccharide augmented MCAF production. These results indicate unique transcriptional and developmental regulation of MCAF mRNA and protein production during pregnancy and chorioamnionitis. Placental MCAF may be involved in the feto-maternal defence mechanism by activating feto-placental and maternal monocytes in chorioamnionitis.

Blotting, Western↗