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Biomedical subjects

K Sawai

Publications and source records attributed to K Sawai.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Prophylaxis of peritoneal carcinomatosis with intraperitoneal administration of cell-adhesion inhibitor, in mice].

DSD was studied for its prophylactic effect against peritoneal carcinomatosis using B-16 melanoma cell line. In in vitro examinations, incubation in medium containing 0.2% DSD significantly inhibited B-16 melanoma cells from adhering both to the plastic wall and the injured peritoneum, as compared to incubation in normal medium. Upon in vivo examination, intraperitoneal administration of 0.2% of DSD (1 ml/mouse) diminished the cancer cell number implanted into the injured peritoneum more than intraperitoneal administration of DSD-free medium.

Animals↗
PubMed1996

Disposition of oligonucleotides in isolated perfused rat kidney: involvement of scavenger receptors in their renal uptake.

The objective of this study was to clarify the renal disposition characteristics of a 20-mer model phosphodiester oligonucleotide and its partially (PS3) and fully (PS) phosphorothioated derivatives, in isolated rat perfused kidney. Venous outflow and urinary excretion pattern, as well as tissue accumulation of radioactivity after bolus injection of 32P-labeled oligonucleotides, were evaluated under both filtering and nonfiltering conditions. The binding affinity of oligonucleotides to bovine serum albumin in the perfusate increased as the number of sulfur atoms present in the oligonucleotide molecules increased, resulting in 21, 60 and 86% binding to bovine serum albumin for phosphodiester oligonucleotide, PS3 and PS, respectively. The apparent steady-state distribution volumes of the oligonucleotides, as calculated from the venous outflow patterns, were larger than that of inulin, which corresponds to the extracellular volume of the kidney, suggesting their interaction with tissue from the vascular space. PS showed the largest distribution volume. Urinary excretion of oligonucleotides was greatly restricted, compared with that of inulin, which was used as a marker of glomerular filtration rate. The accumulation of these oligonucleotides was ascribed to both tubular reabsorption and uptake from the capillary side. The uptake of oligonucleotides from the capillary side increased as the number of sulfur atoms present in the molecules increased, suggesting sulfur atom-dependent interactions between oligonucleotides and renal tissue. In addition, the uptake of PS3 was a saturable process. Furthermore, coadministration of dextran sulfate and polyinosinic acid inhibited the renal uptake of PS3, whereas polycytidic acid and 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid did not, suggesting that oligonucleotides were taken up via the scavenger receptor-mediated process for polyanions. These findings provide valuable information for the development of delivery systems for antisense oligonucleotides.

Animals↗
PubMed1996

The novel role of 3',5'-guanosine monophosphate (cGMP) on the differentiation of trophoblasts: comparison with the effects of 3',5'-adenosine monophosphate (cAMP).

We investigated the effects of 3',5'-guanosine monophosphate (cGMP) on the differentiation of human trophoblasts. Isolated cytotrophoblasts were cultured with 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) or 8-bromoadenosine 3'5-cyclic monophosphate (8-Br-cAMP) and then stained immunocytochemically with anti-human chorionic gonadotropin (anti-hCG) antibody to identify hCG expression as an index of differentiation. Concurrently, morphological changes from cytotrophoblasts to syncytiotrophoblasts were analyzed. Both 8-Br-cGMP and 8-Br-cAMP enhanced the expression of hCG in cultured cytotrophoblasts with the differentiation of cytotrophoblasts to syncytiotrophoblasts dose-dependently. With regard to trophoblast proliferation, 8-Br-cAMP but not 8-Br-cGMP enhanced [3H]thymidine uptake by these cells. hCG, a trophoblast-specific glycoprotein hormone has been identified as a potent growth factor for trophoblasts, also increased [3H]thymidine uptake and the intracellular 3',5'-adenosine monophosphate (cAMP) concentration. However, in this study, hCG did not increase the concentration of intracellular cGMP. We also showed that sodium nitroprusside (SNP), which is a donor of nitric oxide (NO), enhanced intracellular cGMP concentration. These results suggest that cGMP enhances trophoblast differentiation without affecting their proliferation, while cAMP enhances both differentiation and proliferation. We conclude that an alternative pathway mediated through cGMP is responsible for the differentiation of trophoblasts. NO may be involved in trophoblast differentiation with an increase in cellular cGMP level.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Leukemia inhibitory factor (LIF) enhances trophoblast differentiation mediated by human chorionic gonadotropin (hCG).

We investigated the effect of LIF on the differentiation of trophoblasts. Isolated cytotrophoblasts were cultured with and without LIF and cell smears were immunocytochemically analyzed, using anti-hCG antibody. The percentage of differentiated trophoblasts stimulated by 10ng/ml of LIF was about 2.5-fold that in the control culture. The effect of LIF in inducing the differentiation of cytotrophoblasts to syncytiotrophoblasts was dose-dependent. The same effect was shown when hCG was added to the medium. This enhancing effect of LIF on trophoblast differentiation was blocked by adding anti-hCG antibody to the culture system. These results indicate that LIF enhanced trophoblast differentiation by stimulating hCG production in trophoblasts, and not by exerting a direct effect on the trophoblasts.

Abortion, Legal↗
PubMed1995

Activated carbon-oriented gastrectomy for early gastric cancer.

Twenty-two patients with early gastric cancer received injections of activated carbon particles (CH-40) to identify during surgery the location of non-palpable tumours present in the upper portion of the stomach. A few days before surgery, 0.2 ml of CH-40 was injected endoscopically into the gastric muscle adjacent to the cancer. In 20 of the 22 patients, the CH-40-stained area was recognized as a blackened patch on the serosal surface of the stomach which indicated the location of the non-palpable cancer tissue. The surgical margin for gastrectomy was defined as the proximal margin of the carbon-stained area and gastrectomies were performed on the 22 patients. CH-40 injection made it possible to choose the extent of lymph node dissection.

Aged↗
PubMed1995

Rapid and accurate method for delineating cancer lesions in laparoscopic colectomy using activated carbon injection.

The aim of our study was to evaluate the clinical efficacy of preoperative injection of activated carbon in delineation of cancer location in laparoscopic colectomy. Activated carbon particles were injected during endoscopy into the normal colonic wall surrounding cancer lesions in five cases of early colon cancer, prior to laparoscopic surgery. The carbon-stained area was clearly recognizable as a blackened patch on the serosal surface of the colon. Using the carbon-stained area as a reference point, partial colectomies were successfully performed on all five patients. The preoperative injection of activated carbon assisted in the intraoperative delineation of early colonic cancer lesions. This method is recommended for the rapid and accurate delineation of early colonic cancers in laparoscopic surgery.

Aged↗
PubMed1995

Total gastrectomy for early gastric cancer.

A total gastrectomy was performed in 49 patients with early gastric cancer, and the effectiveness of this procedure was evaluated by reviewing the hospital files of the patients. The reasons for this total gastrectomy were as follows: (1) lymph node dissection for 22 patients, (2) surgeon's choice in reconstruction for 10 patients, (3) modification of the surgery from subtotal to total gastrectomy for seven patients, (4) synchronous multiple cancers for seven patients, and (5) cancer in a stomach remnant for three patients. Of 49 patients, 42 had the cancerous lesions in the upper portion of their stomachs. Lymph node involvement occurred in 5 patients, but not in the supra- or infrapyloric lymph nodes. Postoperative complications such as anastomotic leakage, reflux esophagitis and pancreatic fistula occurred in five, four, and two patients, respectively. Postoperative death, including two patients who died within 30 days after the surgery, occurred in 5 patients. Our study showed that total gastrectomy resulted in excessive unnecessary surgery in 39 out of 49 patients (79.6%). We conclude that a total gastrectomy should not be performed on patients with early gastric cancer except for synchronous multiple cancers and for cancers in a stomach remnant.

Anastomosis, Roux-en-Y↗
PubMed1995

Pylorus-preserving gastrectomy with radical lymph node dissection based on anatomical variations of the infrapyloric artery.

We devised a method for performing pylorus-preserving gastrectomy (PPG) with radical lymph node dissection without compromising pyloric blood flow, based on vascular anatomical evaluation of 210 celiac angiograms. The origin of the infrapyloric artery was variable, but consistently supplied blood flow to the pylorus and the posterior wall of the antrum. When the infrapyloric artery originated from the gastroduodenal artery or from one of its pancreatic branches (type A, 88%), the right gastroepiploic artery was divided at its origin, allowing the excision of all adjacent lymph nodes. When the infrapyloric artery originated from the right gastroepiploic artery (type B, 12%), the right gastroepiploic artery was divided distal to the infrapyloric artery origin and the short right gastroepiploic artery remnant was skeletonized of lymph nodes. We have used this technique to perform PPG on 25 patients with early gastric cancer in the middle third of the stomach with minimal morbidity and no mortality.

Adult↗
PubMed1995

Renal disposition characteristics of oligonucleotides modified at terminal linkages in the perfused rat kidney.

To clarify the renal disposition characteristics of oligonucleotides at the organ level, the renal handling of model end-capped oligonucleotides, 3'-methoxyethylamine 5'-biotin-decathymidylic acid containing phosphoramidate modifications at 3'- and 5'-terminal internucleoside linkages (T10) and its phosphorothioate (Ts10), were studied in the perfused rat kidney. In a single-pass indicator dilution experiment, venous outflow and urinary excretion patterns and tissue accumulation of radiolabeled oligonucleotides were evaluated under filtering or nonfiltering conditions. No significant binding to bovine serum albumin (BSA) in the perfusate was observed for T10, whereas more than 90% of Ts10 bound to BSA. The steady-state distribution volume of T10 calculated from the venous outflow pattern was larger than that of inulin, which corresponds to the extracellular volume of the kidney, whereas the distribution volume of Ts10 was larger than that of BSA (the intravascular volume). These results suggested their interaction with the vascular wall. Rapid urinary excretion was observed for T10, similar to inulin used as a marker of golmerular filtration rate. On the other hand, urinary excretion of Ts10 was greatly restricted due to its high binding ability (> 90%) to BSA in the perfusate. A significant amount of T10 and Ts10 was accumulated in the kidney (T10, 1.8% of injected dose; Ts10, 1.3%) compared with inulin (0.2%) and BSA (< 0.1%). The accumulation of these oligonucleotides was ascribed to both tubular reabsorption and uptake from the capillary side. In addition, the uptake of T10 from the capillary side was significantly inhibited by simultaneous injection of dextran sulfate, suggesting that the oligonucleotide was taken up as an anionic molecule. These findings will be useful information for the development of delivery systems for antisense oligonucleotides.

Animals↗
PubMed1995

Detection of monocyte chemotactic and activating factor (MCAF) and interleukin (IL)-6 in human seminal plasma and effect of leukospermia on these cytokine levels.

PROBLEM: To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia. METHODS: Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated. RESULTS: Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 +/- 2.75 micrograms/l) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 +/- 0.53 micrograms/l) and the fertile men (2.78 +/- 0.35 micrograms/l) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 +/- 4.49 ng/l) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 +/- 1.92 ng/l) and the fertile men (6.94 +/- 1.27 ng/l) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma. CONCLUSIONS: These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.

Chemokine CCL2↗
PubMed1995

Soluble interleukin-6 (IL-6) receptor in the sera of pregnant women forms a complex with IL-6 and augments human chorionic gonadotropin production by normal human trophoblasts through binding to the IL-6 signal transducer.

To study the role of soluble interleukin-6 receptor (sIL-6R) during pregnancy, sIL-6R levels in the sera of pregnant women in the first, second, and third trimesters were determined and found to remain unchanged during pregnancy, but were significantly higher than those in nonpregnant women in the follicular, ovulatory, and luteal phases of the menstrual cycle (P < 0.001). IL-6 levels, however, in the sera of pregnant women at all trimesters showed no difference from those in nonpregnant women at any stage of the menstrual cycle. Recombinant sIL-6R (rsIL-6R) augmented hCG production by rIL-6-stimulated trophoblasts dose dependently, but failed to enhance hCG production by unstimulated trophoblasts. rIL-6- and rsIL-6R-induced hCG production was significantly blocked by anti-IL-6R antibody, PM1; antisignal transducing glycoprotein 130 (gp130) antibody, GPX7; or a tyrosine kinase inhibitor, genistein. Thus, sIL-6R in serum from pregnant women forms a complex with placental and decidual IL-6 in a manner similar to trophoblast membrane-bound IL-6R. These two discrete types of IL-6R and IL-6 complex might act cooperatively by binding to gp130 and subsequently evoking tyrosine kinase activity in the trophoblasts to produce hCG in vivo.

Abortion, Legal↗
PubMed1995

Leukemia inhibitory factor produced at the fetomaternal interface stimulates chorionic gonadotropin production: its possible implication during pregnancy, including implantation period.

We investigated the role of leukemia inhibitory factor (LIF) at the implantation site of human embryos. The first trimester decidual tissue produced higher levels of LIF than chorionic tissue, but the decidua produced much smaller amounts of interleukin-6 (IL-6) than the chorion in vitro, as determined by enzyme-linked immunosorbent assay. The reverse transcription-polymerase chain reaction and immunohistochemical analysis revealed the expression and localization, on the trophoblasts, of glycoprotein 130 (gp130), an IL-6 signal transducer receptor component shared by the cytokines such as LIF and IL-6. Trophoblasts stimulated by recombinant LIF (rLIF) produced CG titer at the amount similar to that induced by rIL-6. Recombinant LIF-induced CG production was significantly blocked by anti-gp130 antibody but not by anti-IL-6 receptor antibody, whereas rIL-6-induced CG was completely blocked by both antibodies. Recombinant LIF- and rIL-6-induced CG productions were both significantly blocked by genistein, a tyrosine kinase inhibitor, suggesting an involvement of tyrosine kinase in gp130-mediated CG production. Since CG is capable of stimulating trophoblast growth and differentiation as well as placental metabolism, LIF produced at the fetomaternal interface are considered to stimulate the trophoblasts to produce CG, which may contribute to the maintenance of the placental functions and embryonal growth.

Antibodies↗
PubMed1995

[Clinico-pathological studies on three preoperative combined treatments for rectal cancer].

To prevent postoperative local recurrence of rectal cancer, we treated patients using preoperative hyperthermia (5-6 times), irradiation (total 30 Gy) and 5-fluorouracil suppository (2,000-2,500 mg). The subjects were 31 patients given combined treatments and 28 patients given surgery alone. The results were as follows: 1. Histologically, therapeutic effects were recognized in 80.6% of patients receiving combined treatments. 2. The mean distance from the adventitia to the site of cancer infiltration was 6.54 mm in the combined treatments group and 3.35 mm in the surgery alone group. The difference between the two was significant (p < 0.05). 3. The rate of local recurrence in the combined treatments group was less than that in the surgery alone group. 4. No systemic side effects nor severe complications were observed during hospitalization in the combined treatments group. 5. The survival rate of the combined treatments group was higher than that of the surgery alone group. It was considered that combined preoperative treatments for rectal cancer were beneficial to survival and local control.

Adult↗
PubMed1995

[Endoscopic injection of methotrexate bound to activated carbon particles in the treatment of gastric cancer].

A new dosage formulation (MTX-CH), composed of fine activated carbon particles absorbing methotrexate (MTX), distributes concentrated MTX for long periods of time to the regional lymph nodes as well as to the injection site, in animal experiments. MTX-CH would enhance the therapeutic effects not only on the primary lesion but also on the lymphatic metastasis. As clinical trials, (A) in five patients with early gastric cancer, MTX-CH at 50 to 200 mg/person of MTX was injected endoscopically in and around the primary lesion before operation. Surgically removed specimens showed that three out of the 5 primary lesions had disappeared or were necrotic, and the remaining two lesions had shrunk. (B) Three patients with contraindication to surgery received the endoscopic injection of MTX-CH. The MTX-CH injected at 250 to 1,500 mg/person into and around the primary lesion of relatively early gastric cancer resulted in the complete disappearance of the primary lesions for 14 to 24 months up to the present time without enlargement of the lymph nodes. It was thought that local injection of MTX-CH will be effective therapy, especially for gastric cancer with potential lymphatic metastasis in patients with contraindications to surgery.

Animals↗
PubMed1995

[Trial of a treatment for lymph node metastases in patients with breast cancer using aclarubicin bound to activated carbon particles].

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, was developed for the treatment of lymph node metastases in patients with breast cancer. In a mice experimental model, ACR-CH had superior therapeutic effects on lymph node metastases compared to the same dose of ACR aqueous solution. In clinical trials, patients with breast cancer received a local injection of 10 mg/person of ACR in the form of ACR-CH or ACR aqueous solution just before mastectomy. In the regional lymph nodes removed by the operation, the ACR concentration of 40.7 micrograms/g in patients given ACR-CH was higher than the 25.1 micrograms/g in patients given ACR aqueous solution, whereas in blood plasma the concentration was higher in patients given ACR aqueous solution than in those given ACR-CH.

Aclarubicin↗
PubMed1994

New trends in surgery for gastric cancer in Japan.

Although standard radical gastrectomy for gastric cancer, including lymph node dissection of compartments I and II, has been commonly utilized in Japan, new trends in gastric cancer surgery recently have been developed. In the treatment of early gastric cancer, endoscopic and limited surgeries have become more prevalent, whereas for advanced gastric cancer, super extended radical gastrectomy (SERG) and aggressive adjuvant therapy have been applied. Limited surgery includes wedge resection of the stomach, pylorus-preserving gastrectomy, vagus-preserving gastrectomy, and proximal gastrectomy. The purpose of these more limited techniques is usually to improve quality of life after surgery. Since Takahashi's lymph node staining method using fine activated carbon particles (CH40) made possible systematic para-aortic lymph node dissection, SERG has increased in popularity. The survival rate of patients with para-aortic lymph node metastases who underwent SERG was higher than that of patients who underwent extended radical gastrectomy.

Chemotherapy, Adjuvant↗
PubMed1994

Reduced toxicity of a new formulation--peplomycin adsorbed on activated carbon particles--in mice.

We studied the acute toxicity and pathological effects of peplomycin adsorbed on fine activated carbon particles (PEP-CH) injected subcutaneously in mice. The 50% lethal dose value was 41.2 mg/kg in terms of peplomycin, which was 1.52 times that of the peplomycin aqueous solution (PEP-AQ) of 27.1 mg/kg. Deaths occurred from 5 to 31 days after administration of PEP-CH and from 5 to 22 days after administration of PEP-AQ solution. These figures are remarkably different from another report in which the mice given PEP-AQ died within 10 days.

Adsorption↗