Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 109 records · Page 6Linked to original sources

PubMed1999

The Relationship between Urinary Pyridinoline, Deoxypyridinoline and Bone Metastasis in a Rat Breast Cancer Model.

BACKGROUND: Bone metastasis from breast cancer is often recognized clinically, but there are nonetheless several difficulties in diagnosis. In this study we used an animal model of bone metastasis from breast cancer and clarified the relationship between the urinary Pyd/Cr and Dpd/Cr and the progression of bone metastasis, compared with other bone related markers: serum alkaline phosphatase bone isozyme (ALP-BI), osteocalcin, and calcium. METHODS: The evaluation of bone metastasis was assessed by histological examination of the thoracic and lumbar vertebrae. According to the histological findings 4 weeks after the tumor cell injection, 11 animals were retrospectively divided into 2 subgroups: (1) tumor-bearing rats with bone destruction due to bone metastasis (TBR-BD(+), n = 5), (2) tumor-bearing rats without bone destruction (TBR-BD(-), n =6). These animals were compared to age-matched controls without tumor cell injection (n =6). An additional 5 animals were sacrificed at 2 weeks after the tumor cell injection to evaluate micrometastasis to bone. RESULTS: The values of other markers for bone metastasis in animals with micrometastatic foci in bone marrow did not differ significantly from those of the controls. Pyd/Cr and Dpd/Cr in the TBR-BD(+) group were significantly higher than those of the TBR-BD(-) and the control group (233 +/- 78.3 vs 93.8 +/- 6.5, 98.5 +/- 18.7, 123.1 +/- 35.9 vs 67.9 +/- 6.2, 60.6 +/- 9.8, p< 0.01), while there were no significant differences between TBR-BD(-) and the control. CONCLUSION: Both Pyd/Cr and Dpd/Cr are correlated significantly with the volume of bone metastasis, and are useful for the diagnosis and evaluation of progression of bone metastasis compared with other markers.

Journal Article↗

PubMed1999

Cell-specific expression of the diphtheria toxin A-chain coding sequence under the control of the upstream region of the human alpha-fetoprotein gene.

BACKGROUND AND OBJECTIVES: Development of the system to express a suicide gene selectively in tumor cells is essential for gene therapy. We constructed a plasmid containing the diphtheria toxin A (DTA) fragment linked to human alpha-fetoprotein (AFP) promoter and enhancer, and tested whether it can exert its cytocidal effect selectively on AFP-producing cells. METHODS: The chloramphenical acetyltransferase (CAT) reporter gene or DTA gene was linked to the 5' upstream region of the AFP gene. The plasmids were transfected into AFP-producing or non-producing cells by the lipopolyamine-coated DNA method. Expression of CAT activity and effects on cell growth of transfected cells were assessed. RESULTS: When the AFP-producing cells HuH-7 or HepG2 were cotransfected with CAT reporter plasmid and pAF5.1DTA plasmid, the CAT activity was greatly suppressed. In contrast, cotransfection with pAF5.1DTA-R, the inversely inserted DTA gene, did not inhibit CAT activity. Furthermore, cell growth of HuH-7 cells transfected with pAF5.1DTA plasmid was significantly inhibited compared with HuH-7 cells transfected with DTA-R plasmid. CONCLUSIONS: Our results indicate that selective killing of AFP-producing cells will be attained by introducing the DTA gene linked to the promoter and enhancer region of AFP.

Carcinoma, Hepatocellular↗

PubMed1999

Collagen biosynthesis in gastric cancer: immunohistochemical analysis of prolyl 4-hydroxylase.

BACKGROUND AND OBJECTIVES: The mechanism of the desmoplastic response in gastric carcinoma tissues is largely unknown. The objective of this study is to determine the localization of prolyl 4-hydroxylase (PH), an enzyme that plays a crucial role in collagen biosynthesis. METHODS: Freshly prepared gastric carcinoma tissues from 51 cases, including 13 of the scirrhous type (diffusely infiltrative type), were immunostained by using monoclonal antibodies to human placental PH. RESULTS: Although cytoplasmic staining for PH was observed in both fibroblasts and carcinoma cells, there was increased expression of the alpha-subunit in fibroblasts and no difference in expression between the scirrhous and non-scirrhous type gastric carcinomas. In scirrhous type samples, there was increased PH expression in fibroblasts located in the tumor periphery when compared with fibroblasts in the tumor center. These findings suggested that maintenance of a balance between production and degradation of collagen in gastric carcinoma tissues might be important for stroma formation. CONCLUSIONS: It is speculated that activated fibroblasts participate in collagen biosynthesis at the tumor periphery rather than in the tumor center and that increased collagen biosynthesis at the tumor periphery in scirrhous gastric carcinoma may assist further invasion of tumor cells.

Adenocarcinoma, Scirrhous↗

PubMed1999

Kupffer cell-independent acute hepatocellular oxidative stress and decreased bile formation in post-cold-ischemic rat liver.

The purpose of this study was to examine distribution and time history of oxidative stress during the hyperacute period of reperfusion in the liver grafts undergoing cold ischemia and to investigate roles of Kupffer cells as a potential oxidant source. Rat livers were harvested at 4 degrees C in University of Wisconsin solution and followed by reperfusion with Krebs-Henseleit buffer under monitoring bile excretion. To investigate oxidative changes, laser-confocal microfluorography was performed in reperfused livers preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescence precursor sensing intracellular hydroperoxide generation. Livers undergoing the 16-hour cold storage displayed an impaired recovery of bile acid-dependent bile output concurrent with a marked increase in hydroperoxide generation in hepatocytes, which occurred as early as 5 minutes after the onset of reperfusion, whereas the status of lobular perfusion was well maintained. Pretreatment with liposome-encapsulated dichloromethylene diphosphonate, a Kupffer cell-depleting reagent, did neither alter the reperfusion-induced periportal oxidative changes nor improve the recovery of bile output in the graft. On the other hand, EPCK, a hepatotropic antioxidant composed of vitamin E phosphate ester bound to vitamin C, not only diminished the oxidative changes but also improved the reduction of bile acid-dependent bile output. Furthermore, the reagent was capable of inhibiting H(2)O(2)-induced oxidative stress in cultured hepatocytes. These results suggest that hepatocytes constitute a major site of the oxidative insult triggered through Kupffer cell-independent mechanisms and serve as an important cellular component to be protected by antioxidant therapeutics.

Animals↗

PubMed1999

Laparoscopic ileocecal resection for Crohn's disease associated with intestinal stenosis and ileorectal fistula.

Although a complete remission of Crohn's disease can be induced by conservative therapy, surgical treatment is often required for patients with intestinal stenosis or fistulas, for whom minimally invasive laparoscopic surgery appears to be most appropriate. We herein report on a 26-year-old patient with Crohn's disease, who presented with an ileorectal fistula and severe stenosis of the terminal ileum and thus underwent laparoscopic surgery. The ileorectal fistula was divided intracorporeally using an autostapling device. The return to full activity after laparoscopic surgery is earlier than after open surgery, and the former approach is often beneficial for some patients with Crohn's disease. This is the first report of laparoscopic surgery for Crohn's disease associated with ileorectal fistula.

Adult↗

PubMed1999

Curative laparoscopic surgery for early gastric cancer: five years experience.

Sixty-one patients who were diagnosed with mucosal gastric cancer have been successfully treated with two laparoscopic techniques at our institute from March 1992 to March 1997. One is laparoscopic wedge resection of the stomach using a lesion-lifting method for lesions of the anterior wall, the lesser curvature, and the greater curvature of the stomach. The other is laparoscopic intragastric mucosal resection for lesions of the posterior wall of the stomach and near the cardia or the pylorus. Indications are as follows: (1) preoperatively diagnosed mucosal cancer; (2) <25 mm diameter elevated lesions; and (3) <15 mm diameter depressed lesions without ulcer formation. Patients were discharged in 4 to 8 days uneventfully. There was no major complication or mortality. The resected specimens had sufficient surgical margins horizontally (16 +/- 5 and 8 +/- 4 mm, respectively) and vertically. In one patient histologic examination revealed slight tumor infiltration into the submucosal layer with lymphatic invasion. He underwent gastrectomy with lymph node dissection 1 month after surgery. Otherwise, histologic examination revealed curative surgery. All patients in the series have survived during the 4- to 65-month follow-up period. There have been two recurrences in the series, both of which were found near the staple line 2 years after the initial surgery and were still mucosal lesions. They were successfully treated by open gastrectomy and laser irradiation. A separate early gastric cancer was found 2 years after the initial surgery in one patient, who then underwent curative open gastrectomy. In conclusion, if the patients are selected properly, these laparoscopic procedures are curative, minimally invasive treatment for early gastric cancer.

Adult↗

PubMed1999

Surgical strategy for abdominal aortic aneurysm with concurrent symptomatic malignancy.

In an attempt to improve the guidelines for concurrent management of concomitant abdominal aortic aneurysm (AAA) and symptomatic malignancy, a retrospective study was undertaken. A total of 186 AAA repairs were performed electively, and 25 patients (13.4%) had concurrent symptomatic malignancy from April 1986 to March 1997. Fourteen patients underwent a one-stage operation, including five abdominoperineal rectal resections, four subtotal gastrectomies, three total gastrectomies, and two right hemicolectomies. Eleven others underwent a two-stage operation, including four with total gastrectomy and left hemicolectomy followed by AAA repair, as well as two with right hemicolectomy and one with left hemicolectomy prior to AAA repair. There were no operative deaths or severe postoperative complications. Of the 25 patients, 22 (88.0%) are still alive during follow-up ranging from 8 months to 11 years. Our surgical approach to both lesions is as follows: (1) Using the transperitoneal approach alone, subtotal gastrectomy and abdominoperineal rectal resection can be safely done simultaneously. (2) Although total gastrectomy can also be performed concurrently, the approach used for each lesion is separate. (3) Colorectal resection is generally done separately. However, a one-stage operation can be performed using the thromboexclusion procedure for AAA repair in patients with right-sided colonic cancer or a temporary transverse colostomy for left-sided colorectal cancer.

Aged↗

PubMed1999

Nitrosyl hemoglobin detected by near-infrared spectroscopy in rat liver allografts.

Near-infrared spectroscopy (NIRS) is a noninvasive biomeasurement system with rays in the near-infrared region that possess high permeability to biological tissues. NIRS was applied to liver allografts undergoing rejection in rats treated with deoxyspergualin (DSG) or tacrolimus (FK506). The nitrosyl hemoglobin (Hb) levels detected in the liver grafts increased 3 days and 5 days after grafting in both allogeneic and syngeneic transplantation. The levels on day 8 remained high in the allogeneic graft, but markedly decreased in the syngeneic graft. Although the serum levels of nitrite and nitrate were extremely low 8 days after grafting in allografted recipients treated with DSG or FK506, the nitrosyl-Hb level in DSG-treated graft was much higher than that in FK506-treated graft. There was no significant difference in survival time between DSG-treated and FK506-treated recipients. In conclusion, DSG and FK506 have a different effect on NO production in allografted liver with ongoing rejection, and circulating nitrite and /nitrate levels do not reflect the local levels of NO in the graft.

Animals↗

PubMed1999

Gastric tube-to-tracheal fistula closed with a latissimus dorsi myocutaneous flap.

A gastric tube-to-airway fistula is a very rare complication after esophageal reconstruction. A patient with a gastric tube-to-tracheal fistula that developed more than 9 years after surgery for cancer of the cervical esophagus was treated with transposition of a pedicled latissimus dorsi myocutaneous flap. Careful perioperative respiratory management helped save the patient's life.

Bronchoscopy↗

PubMed1999

Automated and simultaneous identification of microsatellite instability by fluorescence-based polymerase chain reaction (PCR) in four loci.

Genomic instability is sometimes due to impairment of DNA repair systems, which results in a change in the number of microsatellite repeats in tumor cells, produced by slippage during DNA replication. Such abnormal repeats are manifested as microsatellite instability (MSI). We have devised a simple assay using four-color fluorescence for the detection of MSI by an automatic sequencer. Using this method, MSI and loss of heterozygosity (LOH) at four microsatellite loci can be identified simultaneously. We have also developed an algorithm and software for automated analysis of MSI and LOH with this method. Using our method for the detection of MSI in four microsatellite loci and the algorithm and software that we developed, 18 (94.7%) of 19 patients with hereditary nonpolyposis colorectal cancer (HNPCC), meeting the Amsterdam Minimum Criteria, were found to exhibit MSI.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed1999

Effects of invaginating anastomosis in Kasai hepatic portoenterostomy on resolution of jaundice, and long-term outcome for patients with biliary atresia.

BACKGROUND/PURPOSE: This report describes a technique of hepatic portoenterostomy (HPE) to keep sustained bile drainage in biliary atresia patients. In conventional HPE, the medial posterior row of the anastomosis is placed behind the main portal vein. But around both lateral corners where the portal branches enter the liver parenchyma, the anastomosis is placed across and outside of the portal veins. Resultantly, the proximal part of the portal veins become included in anastomosis attaching directly to the dissected area where bile ducts are copious. In a devised procedure designated as invaginating anastomosis (IA), an anastomotic line was placed to invaginate the medial branch of the right portal vein and also placed behind the veins even at their roots. This technique puts all portal branches outside of the anastomosis, preventing cicatricial adhesion at the dissected area with the posterior wall of the veins. METHODS: The effect of IA was evaluated in terms of resolution of jaundice and long-term outcome compared with conventional anastomosis (CA). Group IA consisted of 20 patients and group CA of 18 patients. RESULTS: Patients in whom jaundice resolved included 19 (95%) in group IA and 11 (61%) in group CA (P < .05). Reoperation was needed in only one infant in group IA, and in six in CA (P < .05). In patients with reoperation in group CA, the portahepatis was found to be contracted with dense cicatricial tissues. The survival rates for patients with a native liver, calculated excluding those in whom the cause of death was not liver deterioration, was 87% for IA compared with 41% for CA (P < .05). Averaged biliary atresia prognostic index at the last follow-up evaluation was 20.2+/-24.5 for group IA and 62.6+/-29.8 for group CA (P < .001). CONCLUSION: The invaginating anastomosis in portoenterostomy promised a sustained bile drainage and improved long-term outcome by preventing cicatricial contraction of the portahepatis.

Anastomosis, Surgical↗

PubMed1999

Celiomesenteric anomaly with concurrent aneurysm.

We describe a rare case of a celiomesenteric anomaly with concurrent aneurysm. The patient, a 53-year-old man, had no abdominal pain or discomfort. The presence of a celiac artery aneurysm was suspected on the basis of the results of abdominal computerized tomographic scanning and echo ultrasound scanning performed because of proteinuria. Intra-arterial digital subtraction angiographic results showed the anomaly and aneurysm. Because of the risk of rupture of the aneurysm, the lesion was repaired surgically, with the placement of an interpositional prosthetic graft. We found no previous reports of celiomesenteric anomaly with concurrent aneurysm repaired with prosthetic graft.

Aneurysm↗

PubMed1999

Anthraquinones from hedyotis herbacea

A new anthraquinone, 2-hydroxymethyl-10-hydroxy-1,4-anthraquinone (1), was isolated from Hedyotis herbacea along with three other known derivatives: 1,4-dihydroxy-2-hydroxymethylanthraquinone (2); 2, 3-dimethoxy-9-hydroxy-1,4-anthraquinone; and 1,4-dihydroxy-2, 3-dimethoxyanthraquinone. The structure of 1 was determined based on analysis of its spectroscopic data.

Journal Article↗

PubMed1999

Clinical significance of telomerase activity in the non-cancerous epithelial region of oesophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to examine telomerase activity in affected and adjacent tissue in patients with oesophageal squamous cell carcinoma (SCC). METHODS: Telomerase activity was measured in oesophageal SCC cells, normal oesophageal culture cells, primary cancer tissues and adjacent normal tissues from patients with oesophageal SCC using a polymerase chain reaction-based assay. RESULTS: All oesophageal SCC cells had telomerase activity, whereas normal cultured cells showed no activity. All 57 cancer tissues showed telomerase activity compared with only five (10 per cent) of 50 normal tissues. Cancer cells infiltrating the vessels of mucosal or submucosal tissues in non-cancerous regions were detected in four of five telomerase-positive normal tissues, whereas such infiltration was detected in only three of 45 telomerase-negative normal tissues. CONCLUSION: In patients with oesophageal SCC, measurement of telomerase activity in normal epithelium is a highly sensitive method of detecting the microinvasion of cancer cells.

Carcinoma, Squamous Cell↗

PubMed1999

Intraportal perfusion of prostaglandin E1 attenuates hepatic postischaemic microcirculatory impairments in rats.

BACKGROUND: The efficacy of intraportal perfusion with prostaglandin E1(PGE1) in decreasing postischaemic hepatic microcirculatory damage was studied in rats. METHODS: An extrahepatic portosystemic shunt was created by attaching the spleen to a subcutaneous site on the left lateral wall of the abdomen in male Wistar rats weighing between 200 and 350 g. Four weeks later, when the shunt was mature, the portal vein and hepatic artery were occluded for 60 min. The animals were divided into the following three groups according to the type of intraportal perfusion during the ischaemic phase: group 1 consisted of untreated animals; group 2, animals perfused with lactated Ringer's solution; and group 3, animals perfused with PGE1 (0.1 microg/kg per min). The hepatic microcirculation was observed under an inverted intravital microscope after the injection of fluorescent dyes to label leucocytes and damaged cells 30 and 60 min after reperfusion. The liver was removed 60 min after reperfusion and stained immunohistochemically using 1A29, an anti-rat intercellular adhesion molecule-1 (ICAM-1) antibody. RESULTS: The leucocyte velocity during reperfusion was lowest in group 1 and highest in group 3. Of the three groups, group 3 showed the least leucocyte adhesion to the sinusoidal walls and terminal venules, the lowest damaged cell count and the lowest ICAM-1 expression on the sinusoidal walls. CONCLUSION: The results of this study suggest that hepatic perfusion with PGE1 markedly alleviates microcirculatory damage associated with ischaemia and reperfusion through the inhibition of leucocyte-endothelium interactions.

Alprostadil↗

PubMed1999

Value of dynamic susceptibility contrast magnetic resonance imaging in the evaluation of intracranial tumors.

The degree of tumor malignancy generally correlates to tumor grade, and the direct measurement of tumor vasculature is desired. Dynamic susceptibility contrast magnetic resonance imaging can provide relative cerebral blood volume and, therefore, is one of the most reliable methods to evaluate tumor vasculature in vivo. Tumor vessel size is extremely variable due to complex tumor angiogenesis, and the gradient-echo echo-planar imaging (GE-EPI) technique, which is sensitive to the total vascular bed, is well suited for this purpose. As many studies have shown, dynamic susceptibility contrast magnetic resonance imaging is more useful for grading glioma than conventional magnetic resonance imaging. We found that this technique can also provide supplementary information to differentiate between malignant lymphoma and glioma because the absence of tumor neovascularization of malignant lymphoma leads to low rCBV, which is in contrast to those of malignant gliomas. Indeed, this technique can be used for the differentiation of extra-axial tumors such as between meningioma and neurinoma. Recently, this technique has been focused toward determining the stereotactic biopsy site, monitoring the embolization of effect in meningioma, or evaluation of treatment effects after radiation therapy. However, the value of tumor rCBV is affected by many conditions such as the T1 relaxivity effects of gadolinium in the extravascular space. To establish the usefulness of this technique, further examination will be needed.

Adult↗

PubMed1999

Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C or cisplatin on peritoneal dissemination of human gastric cancer cell line TMK-1 in nude mice.

R-94138, a matrix metalloproteinase inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. When the supernatant of a co-culture of TMK-1 cells and human normal fibroblast cells was subjected to gelatin zymography, it was clear that the protein expression of MMP-2 had been inhibited by R-94138. When TMK-1 was injected intraperitoneally (i.p.) into nude mice at 5 x 10(5) cells/body, the resulting peritoneal dissemination mimicked clinical carcinomatous peritonitis. When the maximum tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the tumor inoculation, peritoneal dissemination was completely inhibited, while the effect of R-94138 was limited when it was given i.p. at a dose of 20 mg/kg in a schedule of q.d. x 5 starting 12 h after tumor injection. MMC and DDP also suppressed peritoneal dissemination when they were administered 1 week after the tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R-94138 inhibited peritoneal dissemination when it was administered i.p. at a dose of 30 mg/kg in a schedule of q.d. x 5 starting from 1 week after tumor injection. The combination of MMC and R-94138 increased the preventive effect on peritoneal dissemination. R-94138 seems to be a promising candidate to prevent peritoneal dissemination of gastric cancer.

Acetamides↗

PubMed1999

Treatment strategy for pancreatic head cancer: pylorus-preserving pancreatoduodenectomy, intraoperative radiotherapy and portal catheterization.

Pancreatic cancer is the disease of gastrointestinal cancer with the poorest prognosis. At present, in addition to surgery, multimodality treatment combining a variety of therapeutic methods is used. We usually employ the following combination of surgery, radiotherapy and chemotherapy: D2 surgery with pylorus-preserving pancreatoduodenectomy (PPPD), intraoperative radiotherapy (IORT), and portal catheterization (PC) with fluorouracil as the chemotherapy. In this study, we made a historical comparison of PPPD and PD and obtained the following findings: (1) PPPD allows almost the same extent of D2 dissection as conventional PD, and achieves radical treatment without any problems; (2) suppression of local recurrence by IORT cannot be expected from the results of the comparison between the four approaches, i.e. surgery alone, surgery + IORT, surgery + PC and surgery + IORT + PC, and (3) the rate of liver metastasis in patients treated by PC was significantly low.

Catheterization↗