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Biomedical subjects

K Sawai

Publications and source records attributed to K Sawai.

At least 55 records · Page 3Linked to original sources

Mp colorectal cancer should be defined as early colorectal cancer.

Little is known about the clinicopathologic features of mp colorectal cancer, defined as a cancer where the depth of invasion is limited to within the mucosa, the submucosa and the proper muscle. This study was designed to determine the clinicopathologic features of mp colorectal cancers. From 1973 to 1993, 83 mp colorectal cancer and 66 sm colorectal cancer patients were treated in our department and were enrolled in this study. During the same period, 66 patients with sm colorectal cancer defined as a cancer where the depth of invasion is limited to within the mucosa and the submucosa, were treated. The clinicopathologic findings of these patients were determined retrospectively from their hospital records. Clinicopathologic differences in sm and mp colorectal cancers were compared with sm and mp gastric cancers. The incidence of mp colorectal cancer increased from 7.9% in 1973-1977 to 16.2% in 1988-1993. An advanced macroscopic appearance, a larger tumor size, lymph node metastasis and lymph vessel invasion were more predominant in mp than sm colorectal cancer. Multivariate analysis demonstrated that these clinicopathologic factors were not statistically independent prognostic factors for mp colorectal cancer patients. There was no statistical difference in postoperative survival between sm and mp colorectal cancer patients. Mp colorectal cancer should be defined as early colorectal cancer, because the postoperative survival rate does not differ between mp and sm colorectal cancers, and the clinicopathologic differences between these two are negligible.

Colorectal Neoplasms↗

Human parvovirus B19 infection resembling systemic lupus erythematosus.

A 39-year-old female visited our hospital because of morning stiffness, arthralgia, skin rash of the extremities and general fatigue. On examination, she also had a malar rash and an oral ulcer. Laboratory findings revealed that antinuclear antibodies were positive and complement component levels (C3, C4, CH50) were all low. Serology for human parvovirus B19 (HPV-B19) was positive for both immunoglobulin (Ig)M and IgG. Gradually, her symptoms improved and laboratory data returned to normal range without medications. This case suggests that HPV-B19 infection may be attributed to the pathogenesis of systemic lupus erythematosus.

Adult↗

[Angiographic diagnosis and management of bleeding from the digestive organs].

Gastrointestinal bleeding is recently seen less often by the angiographer. This is mainly due to advances in endoscopy, and nuclear medicine. When patients with gastrointestinal bleeding are referred, endoscopic diagnosis and therapy should be performed at first. However, when it is impossible to diagnose or to control the bleeding, angiography must be considered as soon as possible. Intra-abdominal bleeding should be diagnosed by angiography at first. In both cases, embolization is generally safe and effective depending on the advance of occlusive agents.

Angiography↗

[What 100 HPN patients taught us].

Recently, Terumo Corporation has developed a new management system, 'Home-Joint', which helps hospitals discharge patients easily. Several hospitals have adopted this system for HPN (home parenteral nutrition) patients, as it can provide discharge program from the hospital and provide items required in alternate site care. This report gives an evaluation of 100 HPN patients who underwent 'Home-Joint' program in 1997. 1) Profiles of patients. Number: 100 (female 47, male 53) Age: 26-96 (61 patients over 70) DIAGNOSIS: cancer 57, others 21, unknown 22 Therapeutic periods: average 53 days (2-617) for terminated 84 patients. Infusion Devices: ambulatory pump 55, stationary pump 41, gravity 4. 2) Important factors for HPN support 1. Be reliable for patients and staff. 2. Train patients well before discharge. 3. The simpler the device the better. 4. Trial or short home-coming required. 3) Issues. 1. Compared with other home therapies, HPN blood access requires much care. 2. Therapeutic period too short. 3. Pay for HPN service too small for a business HPN is very useful for the hospital to discharge the patient comfortably, but requires a complete service system and suitable reimbursement for business.

Adult↗

Analysis of lymph node metastasis in early gastric cancer: rationale of limited surgery.

BACKGROUND: Since the majority of patients with early gastric cancer show long-term survival after surgery, a special attention must be directed to preserving gastric function in these patients. Little is known about the protocol of surgical treatment appropriate for early gastric cancer patients. This study was designed to determine the appropriate surgical procedure for early gastric cancer. METHODS: The clinicopathologic features of 52 patients with node-positive early gastric cancer were reviewed retrospectively from hospital records between 1969 and 1994 and were compared with those of 582 patients with node-negative early gastric cancer. Nodal status of positive nodes in the 52 cases was investigated. RESULTS: Depth of invasion, lymph vessel invasion, and tumor size were associated with lymph mode metastasis. Node-positive patients with early gastric cancer had a poorer survival rate than node-negative patients (P < 0.05). Patients with five or more positive nodes and positive nodes distant from the common hepatic artery showed an extremely poor prognosis. CONCLUSIONS: The surgical procedures most appropriate for the treatment of early gastric cancer are as follows: (1) local gastric resection without lymphadenectomy for mucosal cancers of < 2 cm in diameter and for elevated submucosal cancers of < 1 cm in diameter, (2) gastrectomy with dissection of the perigastric nodes, the nodes along the left gastric artery and the common hepatic artery, for the treatment of other early gastric cancers.

Aged↗

Overexpression of bax enhances the radiation sensitivity in human breast cancer cells.

Bax-alpha, a splice variant of bax which promotes apoptosis, is expressed in many kinds of untransformed cell lines and breast tissue, whereas only weak or no expression could be detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax and neomycin-resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus generated which expressed different levels of bax-alpha. Sensitivity to ionizing radiation (IR) was examined and each was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax, and IR was found to induce intranucleosomal DNA fragmentation in stable transfectant but not in parent cells, thus suggesting that this sensitization is due to apoptosis. We suggest that exogenous bax-alpha expression might therefore be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may potentially have a therapeutic application by enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗

The operative indications for proximal gastrectomy in patients with gastric cancer in the upper third of the stomach.

While proximal gastrectomy is often performed for early gastric cancer in Japan, it remains unclear whether or not proximal gastrectomy should be performed for advanced gastric cancer. This study was designed to determine the operative indications for proximal gastrectomy in patients with gastric cancer in the upper third of the stomach. A total of 1691 patients with gastric cancer were reviewed retrospectively from hospital records during the period from 1969 to 1994, and the clinicopathologic characteristics of 82 patients who underwent proximal gastrectomy were compared with those of 150 patients who underwent total gastrectomy. Lymph node metastasis along the lower part of the stomach was observed in gastric cancers which had invaded beyond the muscularis propria of the stomach, but not in those confined to the muscularis propria. Three patients with gastric cancer that had invaded beyond the muscularis propria and metastasized to nodes along the lower part of the stomach were cured by total gastrectomy. However, there was no difference in the postoperative survival rates of the patients treated with proximal gastrectomy and those treated with total gastrectomy, irrespective of tumor stage and depth of invasion. Thus, proximal gastrectomy should be performed for gastric cancer when the depth of invasion is confined to the muscularis propria of the stomach.

Aged↗

Overexpression of bax sensitizes breast cancer MCF-7 cells to cisplatin and etoposide.

Bax, one of the bcl-2 family genes, is expressed in a number of untransformed cell lines and various breast tissues, whereas only weak or no expression has been detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax; and two unique clones, MCF-7/bax-1 and MCF-7/ bax-2, that expressed different levels of bax were generated. Sensitivity to cisplatin (CDDP) and etoposide (VP-16) was examined and each stable transfectant was more sensitive to these agents than the parental MCF-7 cells. The degree of enhancement in sensitivity to these anticancer agents was dependent on the expression level of bax. The enzyme-linked immunosorbent assay (ELISA), which quantifies DNA damage, demonstrated that this sensitization was due to apoptosis. Thus, we suggest that exogenous bax-alpha overexpression may be one of the factors determining cellular chemosensitivity in MCF-7 breast cancer cells and that it could be applied therapeutically to enhance chemosensitivity in breast cancer cells.

Antineoplastic Agents↗

Analysis of vascular anatomy and lymph node metastases warrants radical segmental bowel resection for colon cancer.

To determine the indications for limited colon cancer surgery in each location, we reviewed the arterial branching patterns and lymph node metastases along the course of specific vascular trunks in 344 colon cancer patients who had undergone preoperative angiography and colectomy with lymph node dissection. Our conclusions are follows: Because the ileocecal artery always arises from the superior mesenteric artery and lymph node metastases of cecum cancer were limited to nodes along the ileocolic artery, cecum cancer can be cured by ileocecal resection. The right colic artery has various origins, and ascending colon cancer shows various patterns of lymph node metastases. Therefore a right hemicolectomy should be performed for ascending colon cancer. The middle colic artery forks into right and left branches, and each branch has different branching variations. If the right colic and middle colic arteries have a common trunk, a right hemicolectomy should be performed for transverse colon cancer on the right side. If the left branch of the middle colic artery has an independent replaced origin, lymph node dissection should be modified according to the variant origin. If the left colic artery and the first sigmoidal artery have a common trunk, the lymph nodes along the common trunk should be removed for sigmoid colon cancer and for descending colon cancer. Of the patients with sigmoid colon cancer, 6.3% also had lymph node metastases along the superior rectal artery. Given that the lymph nodes along the superior rectal artery are skeletonized, sigmoid colon cancer can be also cured by partial sigmoidectomy.

Arteries↗

Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney.

PURPOSE: To clarify the mechanism of the renal clearance of recombinant human interleukin- 11 (rhIL- 1), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. METHODS: The disposition characteristics of (111)In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions. RESULTS: Steady-state distribution volume (Vd) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 microg/kidney was between 0.35 and 0.40 ml/g kidney. However, Vd at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine. CONCLUSIONS: The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.

Animals↗

End results of simultaneous pancreatectomy, splenectomy and total gastrectomy for patients with gastric carcinoma.

A distal pancreatectomy is often performed simultaneously with splenectomy and total gastrectomy in the treatment of gastric carcinoma to facilitate dissection of the lymph nodes around the splenic artery. However, the morbidity of partial pancreatectomy is high. Patients undergoing pancreaticosplenectomy in conjunction with total gastrectomy are subject to leaks from the pancreatic stump, which may cause further complications. We performed a retrospective analysis to evaluate the end results of simultaneous distal pancreatectomy with total gastrectomy. The effect of distal pancreatectomy on survival was studied by examination of the records of 174 patients who underwent splenectomy and total gastrectomy for gastric carcinoma. Of these, 93 underwent distal pancreatectomy. Prognostic factors were determined and were examined in relation to the post-operative complications. There was no significant difference in the 5-year survival of the patients who did or did not undergo distal pancreatectomy. There was no correlation between any prognostic factor and distal pancreatectomy. In contrast, distal pancreatectomy was independently associated with post-operative complications. In this retrospective study, the addition of distal pancreatectomy to splenectomy at total gastrectomy for patients with gastric cancer did not affect survival but was associated with severe complications.

Aged↗

Early gastric cancer mimicking advanced gastric cancer.

The clinicopathological features of 37 early gastric cancers mimicking advanced gastric cancer were reviewed retrospectively, and were compared with 596 other early gastric cancers and 126 mp gastric cancers, defined as gastric cancer invading the muscularis propria of the stomach. A greater tumour size (P < 0.005), submucosal invasion (P < 0.005), lymph node and lymph vessel invasion (P < 0.005) and vascular invasion (P < 0.025) were found more frequently in early gastric cancers mimicking advanced gastric cancers than in other early gastric cancers. There were no significant differences in the clinicopathological findings between early gastric cancers mimicking advanced gastric cancers and mp gastric cancers. Patients with early gastric cancers mimicking advanced gastric cancers showed a lower survival rate than patients with other early gastric cancers, but a higher survival than those with mp gastric cancers. The macroscopic appearance of an advanced gastric cancer was an indicator of massive submucosal invasion and lymph node metastasis in early gastric cancer. As early gastric cancers mimicking advanced gastric cancers showed similar clinicopathological findings to mp gastric cancers, these cancers should be treated as mp gastric cancers.

Female↗

Cell-specific targeting of Sindbis virus vectors displaying IgG-binding domains of protein A.

Sindbis virus can infect a broad range of insect and vertebrate cell types due to the widespread distribution of the cellular receptor for the virus. The development of Sindbis virus vectors that target specific cell types could have important implications for the design of gene therapy strategies. To achieve this goal we have designed and constructed Sindbis virus particles displaying the IgG-binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector has minimal infectivities against baby hamster kidney and human cell lines. When used in conjunction with monoclonal antibodies that react with cell-surface antigens, however, the protein A-envelope chimeric virus was able to infect human cell lines with high efficiency. Infection rates were 90% or higher for human lymphoblastoid cells. A variety of cells could be targeted by changing the monoclonal antibody without generating a new recombinant virus.

Animals↗

Human decidual cell biosynthesis of leukemia inhibitory factor: regulation by decidual cytokines and steroid hormones.

The production of leukemia inhibitory factor (LIF) is suggested to be critical for the successful implantation of blastocysts into decidua, because LIF expression is essential for the implantation of mouse blastocytes. We investigated the regulation of LIF production by decidual cytokines and steroid hormones. Stimulation of decidual cells by interleukin-1, tumor necrosis factor alpha, or transforming growth factor beta augmented LIF production in a dose-dependent manner. Moreover, estradiol, a steroid hormone that increases during ovulation and early pregnancy, also enhanced LIF production in a dose-dependent manner. These responses were blocked by protein kinase C (PKC) inhibitor but not by other kinase inhibitors, suggesting an important role of PKC in decidual LIF production mediated by cytokines and estradiol. We also showed that stimulating decidual cells with LIF failed to stimulate DNA synthesis and prolactin production in these cells. In summary, LIF was mainly localized in the decidual glands and stroma, and its production was increased by cytokines and estradiol in a dose-dependent fashion; but stimulation of decidual cells by LIF did not influence their proliferation or their prolactin production.

Animals↗

Stage-specific requirement of cysteine during in vitro maturation of porcine oocytes for glutathione synthesis associated with male pronuclear formation.

The present study was designed to clarify the duration of maturation of porcine oocytes when cysteine promotes male pronuclear (MPN) formation through oocyte glutathione (GSH) synthesis. When cumulus-oocyte complexes (COCs) were cultured in a serum-free maturation medium supplemented or not supplemented with 0.57 mM cysteine, about 90% of oocytes reached metaphase I (M-I) to metaphase II (M-II) and M-II at 36 and 48 h of culture, respectively. When cysteine was added to medium at 0, 12, 24, and 36 h of culture and COCs were cultured for a total of 48 h, oocyte GSH concentrations at the end of culture and the incidence of MPN formation after sperm penetration in vitro were both higher than the values in oocytes cultured for 48 h without cysteine. In contrast, the GSH concentration at 48 h and the incidence of MPN formation were not increased when cysteine was present only during the first 24 h of maturation culture. When cysteine was added to medium every 3 h from 36 h of culture on, a higher incidence of MPN formation was obtained in oocytes cultured in the presence of cysteine from 36 to 42 h than from 36 to 45 h of culture, although GSH concentrations were higher in oocytes cultured with cysteine from 36 to 42 h than from 39 to 42 h of culture. These results suggest that the presence of cysteine in maturation medium is critical only between 42 and 48 h of culture when porcine oocytes are in the late M-I to M-II stage of development. At that time cysteine is utilized for GSH synthesis, which is subsequently instrumental in the formation of MPN after sperm penetration in vitro.

Animals↗

Amino acids in maturation medium and presence of cumulus cells at fertilization promote male pronuclear formation in porcine oocytes matured and penetrated in vitro.

The present study was conducted to examine the ability of porcine oocytes to achieve male pronuclear (MPN) formation when they are matured and penetrated in vitro under various culture conditions. When cumulus-enclosed oocytes were cultured for 24-48 h in modified Whitten's medium (pH 7.4) supplemented with 10% porcine follicular fluid, 10 IU eCG/ml, and 10 IU hCG/ml (designated mWM-FG), nuclear maturation of oocytes reaching metaphase II was completed by 36 h after the start of culture. However, there were no differences in the proportions (94-95%) of oocytes penetrated in vitro by cryopreserved ejaculated spermatozoa or in the rates (35-45%) of MPN formation between oocytes cultured for 36 and 48 h. When cumulus-enclosed oocytes were cultured for 36 h in mWM-FG supplemented with 2% (v:v) minimal essential medium (MEM) essential amino acids (EAA) with the addition of 0.1 mM glutamine and/or 1% (v:v) MEM nonessential amino acids (NEAA) and inseminated in vitro, 93-97% of oocytes were penetrated regardless of the presence of amino acids during maturation, but the rates of MPN formation were higher in the presence (79-84%) than in the absence (51%) of any amino acids. The addition of EAA+NEAA and/or 0.57 mM cysteine to mWM-FG also did not affect sperm penetration in vitro, while it promoted MPN formation (76-83%) in penetrated oocytes as compared with those matured in the absence of amino acids and cysteine (53%). When oocytes were freed from cumulus cells after culture in mWM-FG, sperm penetration rates were not different between cumulus-enclosed (100%) and cumulus-free (92%) oocytes, but the rate of MPN formation was higher in cumulus-enclosed (53%) than in cumulus-free (28%) oocytes. When EAA+NEAA+cysteine was added to mWM-FG, MPN formation was not improved in cumulus-free oocytes but was much improved (78%) in cumulus-enclosed oocytes. These results indicate that MPN formation in porcine oocytes is promoted by the addition of amino acids and/or cysteine in simple maturation medium and by the presence of cumulus cells at fertilization in vitro.

Amino Acids↗

Selective delivery of 5-fluorouracil (5-FU) to i.p. tissues using 5-FU microspheres in rats.

A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.

Animals↗

Selective drug delivery to peri-tumoral region and regional lymphatics by local injection of aclarubicin adsorbed on activated carbon particles in patients with breast cancer--a pilot study.

ACR-CH, which consists of aclarubicin (ACR) adsorbed onto activated carbon particles, was developed for locoregional chemotherapy for breast cancer. Thirty patients with breast cancer received an ACR (10 mg) injection intra- and peri-tumorally, either as ACR-CH or as ACR aqueous solution (ACR-AQ) 5 min before the operation for breast cancer. The ACR concentrations were significantly higher in the peritumoral regions and regional lymph nodes, and were also significantly lower in the blood plasma in patients given ACR-CH versus patients given ACR-AQ.

Aclarubicin↗