Biomedical subjects

K Sugihara

Publications and source records attributed to K Sugihara.

At least 19 recordsLinked to original sources

PubMed1995

Patterns of recurrence after nerve-sparing surgery for rectal adenocarcinoma with special reference to loco-regional recurrence.

PURPOSE: Since the early 1980s to relieve functional disturbances after rectal excision, we have been performing nerve-sparing surgery for rectal cancer. The aim of this study was to analyze patterns of recurrences, especially concerning causes of local ones. Furthermore, we would like to address the criteria we used in patient selection to effect successful nerve-sparing surgery. METHODS: From 1982 to 1991, 306 patients underwent nerve-sparing operations, which may be categorized into three types: 1) total autonomic nerve preservation (125 cases), 2) complete pelvic nerve preservation (105 cases), and 3) partial pelvic nerve preservation with removal of parasympathetic nerve (79 cases). Single and multivariant regression analyses were conducted to investigate patterns of recurrence, especially causes of local ones. RESULTS: Sixty-five patients (21 percent) developed recurrent tumors, 19 of which (6.2 percent) were local. Using Dukes terms, there were five patients with Dukes A 13 with Dukes B, and 47 (35 percent) with Dukes C stages. Rate of local recurrences was 13 percent in patients with Dukes C tumor. According to single-variant analysis of Dukes C patients, the following factors are thought to influence local recurrences: number of lymph nodes metastases, level of primary growth, and direction of lymphatic spread. Multivariate regression analysis suggested that lymph node metastasis was the most important and influencing factor on local regrowth (P < 0.002). CONCLUSIONS: Compared with local recurrences is so-called extended surgery appeared to be lower. Our current policy is aggressive application of nerve-sparing surgery, even to patients with node-positive rectal cancer, taking into consideration the exact extent of cancer spread. From the viewpoint of neuroanatomy related to mesorectum, we discussed patient determination for our nerve-sparing surgery.

Adenocarcinoma↗

PubMed1995

Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus.

We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b + 2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japanese isolates, we should take more care because genotype 3a is not determined by current typing systems.

Amino Acid Sequence↗

PubMed1995

Continuous hepatic arterial infusion of 5-fluorouracil for unresectable colorectal liver metastases: phase II study.

BACKGROUND: Although hepatic arterial infusion therapy (HAIT) with 5-fluoro-2'-deoxyuridine for colorectal liver metastases yielded a good response, the treatment may be limited by hepatic toxicities. This study was designed to evaluate HAIT by using 5-fluorouracil (5-FU), with the expectation of a good response with little hepatic toxicities. METHODS: HAIT was begun at a dose of 360 mg/m2 of 5-FU for 7 days by using an extracorporeal infusion pump, followed by 180 mg/m2 of 5-FU for 21 days. After a 7-day interval, 180 mg/m2 of 5-FU was infused for 7 days; this 7-day infusion/7-day no infusion cycle was repeated. RESULTS: Fifty-three of the 68 patients who were referred to this study were evaluable. Complete response was observed in two patients and partial response in 25 (response rate of 50.9%), with a median survival time of 11 months: 18 months for 27 responders and 7 months for 26 nonresponders. Gastrointestinal complications were observed in 18 patients: abdominal pain in nine, vomiting in five, and bleeding in four. No hepatobiliary or hematologic toxicities occurred. Infusion-related complications occurred in 20 patients. CONCLUSIONS: HAIT with 5-FU may provide an effect similar to HAIT with fluoro-2' deoxyuridine but without hepatobiliary complications.

Abdominal Pain↗

PubMed1995

Internephron heterogeneity of growth factors and sclerosis--modulation of platelet-derived growth factor by angiotensin II.

We studied the early phase after 5/6 nephrectomy in Munich-Wistar rats to determine whether treatment with angiotensin II receptor antagonist (AIIRA) modulates the expression of platelet-derived growth factor (PDGF) mRNA and its protein among the glomeruli which are undergoing progressive hypertrophy and sclerosis. Average PDGF-B immunohistochemistry staining score (IHS, 0 to 3 scale) in glomeruli and PDGF-B chain mRNA from kidneys were both increased in 5/6 nephrectomy rats (N = 6) versus age-matched normal (N = 5) at week 4, when glomeruli were at early stages of sclerosis (IHS, 0.81 +/- 0.12 vs. 0.19 +/- 0.05; sclerosis index, S.I., 0 to 4 scale: 0.41 +/- 0.04 vs. 0.05 +/- 0.01, both P < 0.05). AIIRA (80 mg/liter drinking water, N = 6) started at time of 5/6 nephrectomy prevented the development of sclerosis (S.I. 0.08 +/- 0.03) and decreased PDGF-B protein (IHS 0.22 +/- 0.08, both P = NS vs. normal), and PDGF-B chain mRNA. In contrast, triple therapy (TRX; hydralazine, reserpine and hydrochlorothiazide, N = 5) in doses which controlled systemic blood pressure resulted in intermediate level of glomerulosclerosis at this early time point of progressive injury. Concurrently, TRX failed to affect the expression of PDGF-B protein (IHS 0.86 +/- 0.19) or its mRNA expression. The PDGF-B distribution was not uniform amongst the glomeruli with varying stages of sclerosis. There was a strong correlation in individual glomeruli of increased PDGF-B staining with early sclerotic changes (P < 0.01), with the disappearance of this correlation in glomeruli with advanced sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1995

Pathologic support for limited hepatectomy in the treatment of liver metastases from colorectal cancer.

OBJECTIVE: The authors determined an appropriate surgical treatment for liver metastases from colorectal cancers. Clinicopathologic features of metastatic lesions of colorectal cancers were studied. SUMMARY BACKGROUND DATA: Major hepatic resection is the usual procedure for treatment of hepatic metastases from colorectal cancers. METHODS: Forty consecutive patients who underwent hepatic resections were prospectively studied, for a total of 89 metastatic liver tumors. RESULTS: Metastatic tumor often extended along Glisson's capsule, including invasion to the portal vein (9 cases), the hepatic vein (3 cases), the bile duct (16 cases), and the nerve (6 cases). The main tumor had small satellite nodules in only one patient, and there were no microscopic deposits in the parenchyma, even within 10 mm from the metastatic tumors. Fibrous pseudocapsule formation was observed in 28 patients. DISCUSSION: The rarity of intrahepatic metastasis from metastatic tumor supports nonanatomic limited hepatic resection as the procedure of choice for metastatic colorectal cancer in the liver. The spread via Glisson's capsule should be taken into consideration for complete tumor clearance.

Adenocarcinoma↗

PubMed1995

Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity.

All disulfide analogs (types I, II and III) of protegrin (PG)-1, an 18-residue antimicrobial peptide having two intramolecular disulfide bonds, were synthesized using regioselective disulfide bond formation. Random air-oxidation of the fully reduced PG-1 formed the type III PG-1. In addition, a type III analog containing an amidated carboxy-terminal residue was also prepared. Each analog showed significant and different antibacterial and anti-human immunodeficiency virus (HIV) activity. Deletion of two disulfide bridges caused a significant decrease in activity.

Amino Acid Sequence↗

PubMed1995

[Does aging influence effect of pirenzepine alone or combination of pirenzepine and famotidine on gastric secretion during anesthesia and surgery?].

Effect of pirenzepine alone or the combination of pirenzepine and famotidine on gastric secretion during anesthesia and surgery was evaluated in 52 elective surgical patients ranged in age from 17 to 68 years. These patients of each group were divided into two subgroups according to their age either 40 years and under or over. The patients underwent orthopedic, ophthalmic, ENT, plastic or non-abdominal general surgery under neuroleptanesthesia except 5 patients who had enflurane or isoflurane anesthesia. They received either pirenzepine 10 mg or the combination of pirenzepine 10 mg and famotidine 20 mg intravenously just before the induction of anesthesia. Volume and acidity of gastric juice were measured for 3 hours after the administration of these agents. Decrease in volume and acidity of gastric juice continued for more than 3 hours after the administration of pirenzepine alone or the combination of pirenzepine and famotidine, and it was more prominent in the combination group than in the pirenzepine group. There was no statistical difference in volume of gastric juice between the patients of 40 years and under in age and those over 40 years in each group. However, the intragastric pH tended to be lower in patients of 40 years and under in age than that in those over 40 years. A percentage of patients who had intragastric pH below 2.5 was larger in the pirenzepine administered patients of 40 years and under in age than that of the remaining patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Small depressed cancer of the large bowel: report of three cases.

This report describes three patients in whom colonoscopy detected small depressed cancers (without an elevated component) that had invaded the submucosa. They represent 0.4% (3/884) of all patients with invasive cancers and 3% (3/101) of patients with submucosal cancers in the National Cancer Center Hospital between January 1990 and February 1994. This type of cancer may have been overlooked in the past because of its small, flat nature. A slight deformity of the lumen, a faint color change (slightly reddish), and a loss of a vascular network pattern were important colonoscopic findings. Small depressed cancers may follow a different pathway to advanced cancer than polypoid cancers, although both pathways are included in the adenoma-carcinoma sequence. We should be aware of these lesions in our efforts to detect colorectal cancers in the early stage.

Adenocarcinoma↗

PubMed1994

The promotion of invasion through the basement membrane of cervical carcinoma cells by fibronectin as a chemoattractant.

An in vitro migration and invasion assay was used as the model system to study the effect of 3T3 fibroblast conditioned medium (FCM) and purified human fibronectin on the invasion of cervical carcinoma cells. The 3T3 FCM significantly enhanced both the migration and the invasion of a cervical carcinoma cell line, HeLa. This enhancement of migration and invasion was inhibited by anti-fibronectin antibody. Purified fibronectin alone enhanced the invasion in a dose-dependent manner for all cervical carcinoma cell lines, HeLa, CAC-1 and TMCC. The pretreatment of cells with cell binding aminosequences, GRGDSP and/or YIGSR blocked the enhancement of cell invasion. The implication of these findings for the invasion of cervical carcinoma is discussed.

3T3 Cells↗

PubMed1994

Endoscopic mucosal resection for colorectal neoplastic lesions.

PURPOSE: Endoscopic mucosal resection, which is a new option for endoscopic polypectomy of colorectal polyps without stalks, was evaluated on its usefulness in polypectomy. METHODS: Three hundred thirty-seven lesions, which were removed by endoscopic mucosal resection between January 1990 and January 1993, were studied. The endoscopic configuration of neoplastic lesions were classified into four types: flat, sessile, large sessile with distinct lobulations, and semipedunculated. RESULTS: The 337 lesions included 243 adenomas, 30 mucosal cancers, 13 submucosal cancers, 3 carcinoids, 43 hyperplastic polyps, and 5 inflammatory polyps. Of the 286 neoplastic lesions, excluding 3 carcinoids, 137 were flat, 81 were sessile, 18 were large sessile, and 50 were semipedunculated. The 137 flat lesions consisted of 125 adenomas, 10 mucosal cancers, and 2 submucosal cancers. The rate of complete removal was related to their size and configuration and was 87 percent in flat neoplastic lesions. Lesion diameters of greater than 20 mm and the large sessile-type configurations were factors that were associated with incomplete removal. Two (0.7 percent) cases were complicated by perforations, and one (0.4 percent) case was complicated by bleeding. CONCLUSION: Endoscopic mucosal resection is an useful option for complete removal of colorectal nonpolypoid adenomas and cancers.

Colonoscopy↗

PubMed1994

Design of variants of the second domain of urinary trypsin inhibitor (R-020) with increased factor Xa inhibitory activity.

The second domain (R-020) of human urinary trypsin inhibitor (UTI) exerts similar inhibitory activities on trypsin, alpha-chymotrypsin, leukocyte elastase, and plasmin to those of UTI itself, and additionally inhibits coagulation factor Xa (FXa) and plasma kallikrein, on both of which UTI has no inhibitory effect. In the present study, we attempted to increase this FXa-inhibitory activity by modeling the structure of R-020-FXa complex and substituting one or two amino acids in R-020 using recombinant DNA technology. Molecular modeling of R-020 and FXa was performed with reference to X-ray analysis of the complex of bovine pancreatic trypsin inhibitor (BPTI) and bovine trypsin to determine the site of amino acid modification. The expression plasmids into which R-020 genes with base substitution were inserted were prepared and introduced into Escherichia coli to express R-020 variants. The resulting variants were purified and their enzyme inhibitory activities were measured. The FXa-inhibitory activity was increased in four variants with single amino acid substitution. With another four variants having two amino acid substitutions involving combinations of the above single amino acid substitutions, the FXa-inhibitory activity was further increased. Because the electrostatic interaction within R-020-FXa complex seemed stronger in these R-020 variants, this increase in FXa-inhibitory effect was speculated to be a consequence of more potent binding between the enzyme and the inhibitor.

Amino Acid Sequence↗

PubMed1994

Mixed connective tissue disease complicated by infection with human immunodeficiency virus.

A case of HIV-infection presenting as mixed connective tissue disease (MCTD) is reported. A 26-year-old woman from Kenya was admitted with the symptoms and laboratory findings of MCTD. Her peripheral CD4 cell count was decreased. She had high titers of antibodies to HIV antigen by a passive agglutination test and an immunofluorescence technique. Moreover, specific IgG and IgM antibodies to HIV antigens were detected by Western blot analysis after complete absorption of the serum in extractable nuclear antigens from calf thymus. While undergoing azidothymidine treatment, she developed AIDS and died of intracranial bleeding. This is the first report of HIV infection associated with MCTD-like symptoms.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Parachordoma of the buttock: an immunohistochemical case study and review.

We report a case of parachordoma occurring in the buttock of a 43-year-old man, and review 20 cases of parachordoma reported in the English literature. The tumor in our case was grossly 3 cm in dimension, solid, lobulated and grayish-white in color. Microscopically, the tumor consisted of epithelioid and spindle cells, and fibromyxoid stroma. The epithelioid cells were immunohistochemically positive for vimentin, S-100 protein, neuron-specific enolase, keratin, carcinoembryonic antigen and epithelial membrane antigen, and negative for HMB45. These findings are similar to those for chordoma rather than extraskeletal myxoid chrondrosarcoma. Although the etiopathogenesis of parachordoma remains obscure, Schwann cells or some other neuron-related cell origin are suspected.

Adult↗

PubMed1994

Reductase activity of aldehyde oxidase toward the carcinogen N-hydroxy-2-acetylaminofluorene and the related hydroxamic acids.

Liver aldehyde oxidase (EC 1.2.3.1) was capable of reducing N-arylacetohydroxamic acids, N-hydroxy-2-acetyl-aminofluorene, N-hydroxy-4-acetylaminobiphenyl and N-hydroxyphenacetin, to the corresponding amides in the presence of an electron donor of the enzyme under anaerobic conditions. When supplemented with an electron donor of the enzyme, a significant reduction of N-hydroxy-2-acetylaminofluorene occurred, which was sensitive to an inhibitor of the enzyme. These observations were made with cytosolic fractions prepared from the livers of rabbits, guinea pigs, rats and mice.

Aldehyde Oxidase↗

PubMed1994

Generation of self HLA-DR-specific CD3+CD4-CD8+ cytotoxic T cells in chronic graft-versus-host disease.

To analyze the mechanism of chronic graft-versus-host disease (GVHD) characteristic of autoimmune disease, we used a cell-mediated lympholysis assay to study the autoreactivity of PBL from two patients after MHC-matched BMT. Our data indicate the induction of CD3+CD4-CD8+ autoreactive cytotoxic T lymphocytes (CTL) in the one patient with chronic GVHD and an important role for allo-non-MHC (minor histocompatibility) antigen-specific CD3+CD4+CD8- helper T cells in this induction. Experiments using HLA-DR gene-transfected mouse L cells as target cells and blocking assays with anti-HLA class I and class II antibodies provided evidence that autoreactive CTL recognized HLA-DR antigen on autologous cells. Analysis of antigen-specific T cell proliferative responses in these patients to examine the effect of self HLA-DR-specific CTL on the antigen presenting cell (APC)-T cell interaction suggested that donor bone marrow-derived self HLA-DR-specific CTL are responsible for the decreased antigen-presenting ability of the patient's APC. These results suggest a new interpretation of the induction mechanism of chronic GVHD and its associated immunosuppression after MHC-matched BMT based on diminished APC function.

Antibodies, Monoclonal↗

PubMed1994

An analysis on the effect of blood transfusion on recurrence and survival in patients undergoing extended lymphadenectomy for colorectal cancer.

In a retrospective study data were collected from 644 patients with cancer of the colon or rectum undergoing curative surgery with extended lymphadenectomy to evaluate a possible effect of blood transfusion, given perioperatively, on tumor recurrence and patient survival. Univariate analysis showed depth of bowel wall invasion, number and level of lymph node metastases to be of highly significant prognostic factors. After 5 years the overall recurrence rate was 16.6% for the non-transfused (n = 223) and 26.1% for the transfused (n = 421; p < .01) patients, and survival rates showed borderline significance favoring the non-transfused patients (90.5% vs. 80.0% after 5 years; p < 0.05). However, after stratification for the prognostically important factors, in a multivariate analysis a possible detrimental effect of perioperative blood transfusions could not be demonstrated.

Adenocarcinoma↗

PubMed1994

Antiproliferative lymphokine production by human peripheral blood lymphocytes and lymph node lymphocytes detected by a modified double layer soft agarose clonogenic assay.

The double layer soft agarose clonogenic assay using colony formation of target cells as an endpoint was adapted for the detection of antiproliferative lymphokine production from peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL). The colony formation of cervical cancer cell lines, HeLa, CAC-1, and TMCC, in the upper layers was significantly inhibited by the inclusion of either PBL or LNL pretreated with PHA in the lower layers. Without stimulation by PHA, neither resident PBL nor LNL exhibited antiproliferative activity on the tumor cells in the upper layers. The antiproliferative activity against target cells increased in relation to the density of lymphocytes in the lower layers, and was dependent on protein synthesis by lymphocytes. Since the cell to cell contact between the effector cells and target cells is not possible in this assay, the reduction of colony formation should be attributed to soluble factor(s) that were secreted from the lymphocytes. Additionally, an antibody against IFN-gamma neutralized most of the antiproliferative activity, and equivalent levels of IFN-gamma were found to be present in the supernatant of PBL and LNL lower layers by a radioimmunoassay. The double layer soft agarose assay system should thus serve as a useful method for studying antiproliferative lymphokine production by lymphocytes.

Animals↗

PubMed1994

Resection for multiple metastatic liver tumors after portal embolization.

BACKGROUND: Five patients with bilateral multiple liver metastases (3 to 12 lesions) from colorectal cancer who underwent extensive liver resection after portal embolization are described. METHODS: Portal embolization of the right portal branch was performed 9 days to 8 months before hepatic resection. The location and number of metastases were determined by intraoperative ultrasonography at the time of liver resection to accomplish complete resection of the tumors. Extended right lobectomy was carried out in four patients, two of whom underwent additional wedge resection of nodules located in the left lateral segment. The other patient underwent right lobectomy associated with local resection of the tumor in the left lobe. RESULTS: The postoperative course in the five patients was uneventful, with no serious complication or liver dysfunction. Although one patient died of recurrence 28 months after liver resection, the remaining four patients were alive and free of cancer between 36 and 74 months after hepatectomy. CONCLUSIONS: The presence of bilateral multiple (four or more) metastatic liver lesions from colorectal cancer is not considered a contraindication for hepatic resection if thorough examination of the liver is performed with intraoperative ultrasonography and the surgical risk is minimal. Portal embolization appears effective for increasing the safety of hepatectomy for patients with small metastases who require major right-sided resection combined with wedge resection of the left lobe.

Adult↗