Biomedical subjects

Y Kasai

Publications and source records attributed to Y Kasai.

At least 55 records · Page 3Linked to original sources

PubMed1999

Phase II trial of 5-fluorouracil and low-dose cisplatin in patients with squamous cell carcinoma of the esophagus.

A phase II study was conducted to determine the clinical efficacy and toxicity of 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) in patients with squamous cell carcinoma of the esophagus. Chemotherapy consisted of 5-FU at a dose of 330 mg/m2 per day, given as a 24-h infusion on days 1-7, and CDDP at a dose of 6 mg/m2 per day, given as a 2-h infusion on days 1-5. Either two or four cycles of chemotherapy were administered to 20 patients with stage III advanced esophageal carcinoma. All 20 patients were then assessed for response and toxicity. An objective response was demonstrated by 11 of the 20 patients, with one complete response (CR) and ten partial responses (PR), bringing the response rate to 55%, with a 95% confidence interval of 27% to 83%. Surgical resection of the tumor was performed in all 20 patients. One patient was found to have a grade 3 histological CR. The median survival of all the patients was 20.5 months, with a range of 4.5 to 48.0 months. Neutropenia and thrombocytopenia developed in five (25%) and two (10%) patients, respectively, and the nonhematologic toxicities were insignificant. The findings of this phase II study indicate that preoperative treatment using 5-FU and low-dose CDDP chemotherapy for patients with advanced esophageal carcinoma appears to achieve a high response rate after short-term administration without affecting the quality of sophisticated lymph node dissection.

Aged↗

PubMed1999

On-line measurement of adenosine triphosphate and catecholamine released from adrenal chromaffin cells.

Adenosine triphosphate (ATP) and catecholamine (CA) released from cultured porcine adrenal chromaffin cells were continuously measured with an ATP photometer (luciferin-luciferase method) and electrochemical detector, respectively. Application of acetylcholine (ACh, 0.1 mM) or high K+ (60 mM) caused increases of ATP and CA in perfused effluent with the same time course. The peak molar ratio of CA to ATP in the effluent was about 10 for ACh and high K+ stimulation. The high-performance liquid chromatographic (HPLC) analysis of adenine nucleotides in the collected effluent revealed that the relative amounts of ATP, ADP and AMP were almost the same throughout the period of stimulation, suggesting that ATP breakdown in the effluent was constant. Changes in the peak molar ratio of CA to ATP appearing in the effluent did not occur with repetitive high K+ or sustained Ba2+ stimulation (5 mM). The similarity between the time courses of ATP and CA appearing in the effluent suggests that releasable chromaffin granules have a constant molar ratio of CA to ATP. The on-line system developed is a simple and rapid method for examining ATP and CA secretion, simultaneously.

Acetylcholine↗

PubMed1999

Expression of midkine in the early stage of carcinogenesis in human colorectal cancer.

It has been suggested that a heparin-binding growth factor, midkine (MK), plays an important role in carcinogenesis because of its frequent overexpression in various malignant tumours. To clarify whether or not MK contributes to the early stage of carcinogenesis, we examined the status of MK mRNA in 20 adenomas with moderate- and severe-grade dysplasia, 28 carcinomas and 28 corresponding normal tissues, by means of Northern blotting. The MK expression level was significantly more elevated in adenomas than in normal tissues (P < 0.001, unpaired Student's t-test). A difference was also observed between carcinomas and the corresponding normal tissues (P < 0.04, paired Student's t-test). Moreover, MK immunostaining was positive in the adenomas with moderate- and severe-grade dysplasia and in the carcinomas, but not in mild-grade dysplasia or in normal tissues. These findings were in line with those on Western blotting. In three patients with both adenomas with moderate- or severe-grade dysplasia and carcinomas, elevated MK expression was observed in the neoplastic lesions. This is the first report of the association of elevated MK expression with the early stage of carcinogenesis in humans.

Adenoma↗

PubMed1999

[Treatment of solid tumor by a direct electric current].

This is a case report of a 37-year-old Japanese married female with laryngeal sarcoma, treated by direct electric current so as to obtain remission for more than 4 years without signs of recurrence. Due to her hoarseness and laryngeal numb feeling she underwent a laryngeal examination including a biopsy, resulting in a diagnosis of sarcoma. She refused a total laryngectomy and was given Cobalt treatment of 40 Grey. In the following several months, no improvement was observed, objectively or subjectively. In Nagoya University Hospital the patient then received direct electric current therapy of 36 Coulombs through two platinum electrodes inserted into the tumor under a CT guide, pericutaneously. Two months later, as the hoarseness remained in spite of some improvement, she underwent another session of direct electric current therapy of 14.4 Coulombs through the platinum electrodes by bronchoscope-guided direct insertion. Her hoarseness soon disappeared thereafter and there was a regression of the tumor in 6 months. She did well thereafter without any signs of recurrence for 4 years. Clinical treatment of solid tumors with electric treatment with direct electric current has been done in more than 8,000 cases with CR in 25% of all cases and PR in 50%. Its mechanism, however, remains unclear. In our experimental animal studies, apoptosis was observed. It is considered that this electric therapy using direct electric current will be recognized as one method to treat solid tumors.

Adult↗

PubMed1999

Petroleum biodegradation in marine environments.

Petroleum-based products are the major source of energy for industry and daily life. Petroleum is also the raw material for many chemical products such as plastics, paints, and cosmetics. The transport of petroleum across the world is frequent, and the amounts of petroleum stocks in developed countries are enormous. Consequently, the potential for oil spills is significant, and research on the fate of petroleum in a marine environment is important to evaluate the environmental threat of oil spills, and to develop biotechnology to cope with them. Crude oil is constituted from thousands of components which are separated into saturates, aromatics, resins and asphaltenes. Upon discharge into the sea, crude oil is subjected to weathering, the process caused by the combined effects of physical, chemical and biological modification. Saturates, especially those of smaller molecular weight, are readily biodegraded in marine environments. Aromatics with one, two or three aromatic rings are also efficiently biodegraded; however, those with four or more aromatic ring are quite resistant to biodegradation. The asphaltene and resin fractions contain higher molecular weight compounds whose chemical structures have not yet been resolved. The biodegradability of these compounds is not yet known. It is known that the concentrations of available nitrogen and phosphorus in seawater limit the growth and activities of hydrocarbon-degrading microorganisms in a marine environment. In other words, the addition of nitrogen and phosphorus fertilizers to an oil-contaminated marine environment can stimulate the biodegradation of spilled oil. This notion was confirmed in the large-scale operation for bioremediation after the oil spill from the Exxon Valdez in Alaska. Many microorganisms capable of degrading petroleum components have been isolated. However, few of them seem to be important for petroleum biodegradation in natural environments. One group of bacteria belonging to the genus Alcanivorax does become predominant in an oil-contaminated marine environment, especially when nitrogen and phosphorus fertilizers are added to stimulate the growth of endogenous microorganisms.

Biodegradation, Environmental↗

PubMed1998

Liver-type arginase in serum during and after liver transplantation: a novel index in monitoring conditions of the liver graft and its clinical significance.

We quantified liver-type arginase in sera of 47 patients undergoing partial liver transplantation with use of an ELISA method. The level of liver-type arginase fluctuated slightly beyond the normal range in successful liver recipients, while it changed more drastically or precipitously in unsuccessful ones, accompanying or unaccompanying elevation of AST and ALT levels. A higher elevation pattern of the arginase level (above 100 ng ml-1) was observed in each of the unsuccessful recipients with critical condition, except for one patient. Other hepatic markers (LDH, ALP, and T-BIL) remained relatively unchanged until the terminal stage of deceasing patients. The finding that the liver-type arginase emerged in large quantity in the blood stream immediately after reperfusion of the liver graft indicates that the enzyme leaks out of hepatocytes damaged, presumably, by storage in the absence of circulation. A half-life of the liver-type arginase in the human blood was estimated to be 1 h, that is clearly shorter than that of AST. The short half-life of the arginase appears to be ascribable, at least partly, to formation of an immune complex with circulating autoantibody which appears in many liver recipients. These results suggest that liver-type arginase behaves uniquely in the serum among many hepatic enzymes, and could serve as a distinct marker of hepatic lesions, particularly during and after liver transplantation.

Adolescent↗

PubMed1998

Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells.

BACKGROUND AND OBJECTIVE: Peritoneal dissemination and hepatic metastasis commonly occur after patients with pancreatic cancer have undergone surgery. It is thought that specific adhesion molecules play corresponding roles in cancer metastasis. STUDY DESIGN/MATERIALS AND METHODS: We conducted in vitro and in vivo studies to assess the role of adhesion molecules in these processes, using SW1990 cells derived from human pancreatic cancer. RESULTS: SW1990 cells pronouncedly expressed sialyl Lewis(a) (s-Le[a]) and sialyl Lewis(x) antigens (s-Le[x]), CD44H, and beta1 integrin. Also, SW1990 cells showed a strong binding activity to IL-1beta activated human umbilical vein endothelial cells, cultured murine endothelial cells (F-2 cells), and human peritoneal mesothelial cells. Invasive ability of SW1990 cells to F-2 cells was also observed. The adhesion leading to implantation of cancer cells to endothelial cells were inhibited by treatment with the antibodies against s-Le(a) and against beta1 integrin, respectively. Treatments with the antibodies against s-Le(a) and beta1 integrin each inhibited the development of liver metastasis in nude mice with SW1990 cells. The adhesion of SW1990 cells to peritoneal mesothelial cells was markedly inhibited by antibodies each against CD44 or beta1 integrin, but was completely blocked by using a combination of these two antibodies. These antibodies inhibited the dissemination of SW1990 cells in the peritoneal cavity of nude mice and prolonged their survival. CONCLUSION: These findings suggest that s-Le(a) and integrin mediate the process from adhesion to implantation of SW1990 cells to endothelial cells, and CD44 and integrin play important roles in the initial attachment of SW1990 cells to mesothelial cells. It is thus speculated that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of pancreatic cancer metastasis.

Animals↗

PubMed1998

Preoperative embolization therapy for esophageal operation.

BACKGROUND AND OBJECTIVES: Since 1993, we have performed preoperative embolization therapy (PET) in an attempt to augment the blood flow of the gastric tube and prevent anastomotic leakage after esophageal resection. The clinical effects and complications associated with PET are reported. METHODS: The femoral artery was punctured and the left gastric artery, right gastric artery, and splenic artery underwent embolization, leaving the right gastroepiploic artery as the only patent feeding artery for the stomach. PET was performed in 54 patients, and data concerning blood flow of the stomach before and after the construction of the gastric tube were available in 51 patients. Of the 25 patients who were operated in the same period without undergoing PET, similar data were available in 20 patients. RESULTS: In the group of patients who underwent PET, the blood flow of the gastric tube after its construction was 67% of the value measured at the upper part of the stomach just after opening the abdominal cavity. For those who were not pretreated by PET, it declined to 33%. CONCLUSIONS: PET for esophageal cancer is a safe procedure that contributes to the decrease in the frequency of anastomotic dehiscence after esophageal operation, owing to the augmented tissue blood flow of the upper portion of the stomach following the construction of gastric tubes.

Anastomosis, Surgical↗

PubMed1998

Effect on colon cancer cells of human interferon-beta gene entrapped in cationic multilamellar liposomes.

When cultured cells of human colon cancer cell line SW480 were transfected with human interferon-beta (hIFN-beta) gene by means of cationic multilamellar liposomes, the endogenously produced hIFN-beta exhibited a remarkable anti-proliferative effect on the cells, which was more effective than that of exogenously added hIFN-beta. This effect lasted for several days, and was blocked completely by the addition of sufficient amounts of anti-hIFN-beta antibody. From experiments using a transwell plate and an infusion pump, we found that endogenously produced hIFN-beta acted effectively on the cells around the transfectants and that the growth-inhibitory effect was totally retained upon continuous dilution of the medium. These data indicate that hIFN-beta expressed endogenously by transfer of its gene acted on these cancer cells mainly in a paracrine manner. Although the transfection with hIFN-gamma gene also revealed a definite growth-inhibitory effect on the same tumor cells, the extent was less than that of hIFN-beta gene.

Antibodies↗

PubMed1998

Specification of the Drosophila CNS midline cell lineage: direct control of single-minded transcription by dorsal/ventral patterning genes.

The Drosophila CNS consists of a bilaterally symmetric group of neurons separated by a discrete group of CNS midline cells. The specification of the CNS midline cell lineage requires transcription of the single-minded gene. Genetic evidence suggests that a group of transcription factors, including Dorsal, Snail, Twist, and Daughterless:: Scute, is required for initial single-minded transcription. Comparison of the DNA sequences of the single-minded gene regulatory regions between two Drosophila species reveals conserved sequence elements. Biochemical studies using purified proteins indicate that a number of these conserved sequences represent binding sites for Dorsal, Snail, and Twist. In vitro mutagenesis combined with germline transformation indicates that these binding sites are required in vivo for single-minded mesectodermal transcription. These results show that single-minded transcription and, thus, CNS midline specification is directly controlled by dorsal/ventral patterning transcription factors. They also suggest a model in which multiple transcriptional activators function in a cooperative, concentration-dependent mode in combination with a transcriptional repressor to restrict single-minded transcription to the CNS midline precursor cells.

Amino Acid Sequence↗

PubMed1997

Endothelium-dependent frequency modulation of Ca2+ signalling in individual vascular smooth muscle cells of the rat.

1. We visualized intracellular Ca2+ concentration ([Ca2+]i) changes, using fluo-3 as an indicator, of individual vascular smooth muscle cells and endothelial cells within intact rat tail arteries by confocal microscopy. 2. Using a piezo-driven objective, we focused on endothelial and smooth muscle cell layers alternately to obtain Ca2+ images of their cells. In the presence of 1 microM acetylcholine (ACh), individual endothelial cells responded with intermittent increases in the [Ca2+]i (Ca2+ oscillations). At the same time, the frequency of Ca2+ oscillations in smooth muscle cells induced by electrical stimulation of the perivascular sympathetic nerve was greatly decreased. 3. A [Ca2+]i rise during the oscillations in the endothelial cells propagated in the form of a wave along the long axis of the cells. 4. In the presence of a NO synthase inhibitor, no significant inhibitory effect of ACh on the Ca2+ signalling in the vascular smooth muscle cells was detected, although the Ca2+ oscillations in the endothelial cells persisted. 5. The inhibitory effect of ACh on the frequency of Ca2+ oscillations in the vascular smooth muscle cells was mimicked by 1 microM sodium nitroprusside, a NO donor. 6. These results indicate that Ca2+ waves and oscillations in vascular endothelial cells regulate NO production, which modulates vascular tone by decreasing the frequency of Ca2+ oscillations in smooth muscle cells activated by sympathetic agonists.

Acetylcholine↗

PubMed1997

Altered mRNA expression of specific molecular species of fucosyl- and sialyl-transferases in human colorectal cancer tissues.

Human colorectal cancers express various cancer-associated carbohydrate determinants such as Lewis Y or sialyl Lewis A, suggesting a considerable alteration in glycosyltransferase activities occurring upon malignant transformation. We investigated the mRNA amounts of fucosyltransferase (Fuc-T) and sialyltransferase (ST) isoenzymes, including Fuc-T III, IV, V, VI and VII and ST-3N, ST-30 and ST-4, in human colorectal cancer tissues by Northern blotting and RT-PCR. Regarding fucosyltransferases, mRNA of Fuc-T III and VI was not significantly altered, and only Fuc-T IV mRNA showed a moderate increase in cancer tissues when compared with adjacent non-malignant colonic epithelia taken from the same patient (273 +/- 96%; p < 0.001). The moderate increase of Fuc-T IV message may be related to an enhanced expression of Lewis Y in colon cancer tissues. In the ST isoenzymes, mRNA for ST-3N remained unchanged, whereas that for ST-4 decreased significantly in cancer tissues, to 32 +/- 29%, (p < 0.005). The most remarkable finding was that the message of ST-30 was prominently increased in cancer tissues compared with non-malignant colorectal mucosa. When further investigated by quantitative RT-PCR assays on a larger series of patients with colorectal cancers, the average increase in mRNA for ST-30 was 459 +/- 200% compared with that in adjacent non-malignant epithelium (significant at p < 0.0001). The increase of ST-30 message was more prominent in the cancer tissues strongly expressing sialyl Lewis A than in the cancer tissues expressing sialyl Lewis A only weakly or moderately (significant at p < 0.05). The marked increase in the message of ST-30 is suggested to be related to an enhanced expression of sialylated carbohydrate determinants in colon cancer tissues including sialyl Lewis A, since the enzyme exhibited a significant activity against the type 1 chain carbohydrate substrate and produced the precursors for sialyl Lewis A synthesis, when its cDNA was expressed in Cos-7 cells.

Adenocarcinoma↗

PubMed1997

Adhesion molecules and TGF-beta1 are involved in the peritoneal dissemination of NUGC-4 human gastric cancer cells.

Peritoneal dissemination frequently occurs after surgery in patients with gastric cancer. The presence of peritoneal metastasis after surgery affects prognosis. Very little is known about the biochemical processes involved in the initial attachment of gastric cancer cells to peritoneal mesothelial cells. We conducted in vitro and in vivo studies to assess the role of adhesion molecules and TGF-beta1 in this process, using 4 cell lines derived from human gastric cancers. NUGC-4 cells, which disseminate early after inoculation into the abdominal cavity of nude mice, predominantly express CD44H and beta1 integrin. We found that NUGC-4 cells adhered to monolayers of mesothelial cells more firmly than to other cell lines. Adhesion of NUGC-4 cells to mesothelial cells was partially inhibited by antibodies against CD44H or the beta1 subunit of integrin and was completely blocked by a combination of these 2 antibodies. Treatment with ligands for CD44H and beta1 integrin also inhibited adhesion. In the NUGC-4 cell culture medium, larger amounts of TGF-beta1 were detected in relation to the increase in cancer cells than in the other cell lines. TGF-beta1 increased the expression of CD44H in NUGC-4 cells and in mesothelial cells and augmented adhesion and implantation of NUGC-4 cells to mesothelial cells accompanied by accumulation of extracellular matrix (ECM) components. Treatment with antibodies against both CD44H and beta1 integrin inhibited the dissemination of NUGC-4 cells in the peritoneal cavity of nude mice and prolonged their survival time. Our findings suggest that CD44H and integrins mediate the initial attachment of gastric cancer cells to mesothelial cells and that TGF-beta1 participates in the promotion of the disease. Increased expression of CD44H and of the amount of ligands for CD44H and integrins induced by TGF-beta1 promotes early development of peritoneal dissemination.

Animals↗

PubMed1997

Peritoneal washing cytology combined with immunocytochemical staining and detecting mutant K-ras in pancreatic cancer: comparison of the sensitivity and availability of various methods.

Peritoneal metastases are the second most common site of involvement, following the liver, in pancreatic cancer. Thus, we performed peritoneal washing cytology at laparotomy to diagnose accurately the intraperitoneal spread of carcinoma cells to determine the appropriate therapy. Peritoneal washings were collected at laparotomy from 20 Japanese pancreatic carcinoma patients at Nagoya University Hospital between April 1993 and December 1994. From centrifuged deposits, we examined the cytology by three methods as follows. The first method was conventional cytology, including May-Grünwald and Giemsa, Papanicolaou, periodic acid-Schiff, and Alcian blue. The second method was immunocytochemical staining, using antibodies to carbohydrate antigen (CA19-9) and carcinoembryonic antigen. After extracting DNA from the remaining pellet, we studied the last method, detecting K-ras point mutation, by two-step polymerase chain reaction and restriction fragment length polymorphism analysis. In two cases, peritoneal metastases were macroscopically recognized, and the results of all three methods were positive. In the two other cases, where peritoneal dissemination was not macroscopically recognized, the judgments of conventional cytological study and detecting K-ras point mutation were negative. However, a few malignant cells were found by the immunocytochemical staining method. Judging from their clinical course, the positively stained cells were suggestive of malignancy. At present, the immunocytochemical staining method is the most sensitive of these three methods in peritoneal washing cytology. However, preserving DNA is suitable for repeated examination, and a modified method can be applied. If the sensitivity increases, the method of detecting K-ras has the potential to become the standard for peritoneal washing cytology in pancreatic cancer.

Adult↗

PubMed1997

Alternative splicing of the FHIT gene in colorectal cancers.

In the present study, we examined the status of the FHIT gene in 112 colorectal cancer and 137 colorectal adenoma specimens. In a total of 5 specimens (4 colorectal cancers and 1 colorectal adenoma), a common smaller product was detected in addition to the normal size product. This smaller product had lost exon 4, the 5' noncoding region of the FHIT gene, owing to alternative splicing. Moreover, all of the 5 tumors with alternative splicing were located lower on the rectum than the anterior peritoneal reflection.

Acid Anhydride Hydrolases↗

PubMed1997

Clinical usefulness of urinary CrossLaps as a sensitive marker of bone metabolism.

CrossLaps peptide [Glu-Lys-Ala-His-Asp-Gly-Gly-Arg], a part of the C-telopeptide of the alpha 1-chain of type I collagen of bone, is a recently developed biochemical marker of bone turnover. In this study, the clinical utility of measurement of urinary CrossLaps was investigated in eleven premenopausal women who received a gonadotropin-releasing hormone (GnRH) agonist for 6 months for treatment of adenomyosis (n = 1) or leiomyomas (n = 10). Along with urinary CrossLaps, the levels of various biochemical markers, and serum estradiol, calcitonin and intact parathyroid hormone (i-PTH) were measured, and lumbar spine bone mineral density (BMD) was also monitored before, during, and at the end of the course of GnRH agonist therapy. Apart from CrossLaps, markers of bone resorption tested were urinary pyridinoline, deoxypyridinoline and hydroxyproline. Markers of bone formation tested were serum osteocalcin and bone-specific alkaline phosphatase (B-ALP). Serum estradiol levels decreased to undetectable levels at 2 months of GnRH agonist therapy. The values for all biochemical markers increased significantly throughout the therapy. The degree of an increase in CrossLaps levels was greater than that in all other markers. Mean lumbar spine (L2-L4) BMD was decreased by 7.2% at 6 months of treatment. The percent change in BMD at 6 months of treatment correlated inversely with the percent change in CrossLaps levels from the baseline to 1, 2, and 5 months of treatment. These results indicate that measurement of urinary CrossLaps might be a useful tool to predict the risk of bone loss caused by hypoestrogenism including GnRH agonist therapy.

Adenomyoma↗

PubMed1997

[Effects of carcinostatic agents in the hematogenous metastasis of cancer].

The experimental studies in vitro and in vivo were performed to investigate the effects of carcinostatic agents in the adhesion of cancer cells to endothelial cells. Certain carcinostatic agents induce the expression of E-selectin on endothelial cells and enhance the expression of carbohydrate ligands on cancer cells. Consequently, increased adhesion of cancer cells to endothelial cells was observed by the treatment of carcinostatic agents. In the trans-splenic hepatic metastasis model using nude mice, the augmentation of cancer metastasis was observed by the treatment of carcinostatic agents. From the above, we concluded that carcinostatic agents may increase the metastatic ability of cancer cells in patients with cancer.

Animals↗

PubMed1997

[Diagnosis of local recurrence of colorectal cancer, using PET and immunoscintigraphy by means of 131I or 111In anti-CEA monoclonal antibody].

The accurate and early diagnosis of the tumor in the point of the size, the location, the depth of invasion of other organs or the stages of the recurrent cancer became much more important than before, not only for the selection of the treatment method but also for the decision of the quality of the operation for preserving the function as much as possible for the quality of the life of the patient. The usefulness of positron emission tomography (PET) and immunoscintigraphy by means of 131I or 111In anti-CEA onoclonal antibody for the diagnosis of the recurrent colorectal cancer had been confirmed in clinical use of colorectal cancers. No adverse effect of this monoclonal anti-body of the mouse was seen in this studies. The differential absorption ratio (DAR) was useful indicator in PET-imaging to differentiate the true tumor tissue from the scar tissue or granulation-tissue around the tumor. Even though the imaging, structure of PET is inferior to those of CT or MRI, the imaging of PET reflects the biological character of tumor, itself and makes the more accurate diagnosis possibly by combined use with regular CT and MRI.

Adult↗