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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 181 records · Page 10Linked to original sources
PubMed2000

Clinicopathological studies of esophageal carcinosarcoma: analyses of its morphological characteristics using endoscopic, histological, and immunohistochemical procedures.

BACKGROUND AND STUDY AIMS: Carcinosarcoma of the esophagus is a rare malignant neoplasm consisting of both carcinomatous and sarcomatous components, which characteristically forms polypoid tumors. PATIENTS AND METHODS: Seven carcinosarcomas were analyzed using endoscopic, histological, and immunohistochemical procedures. Endoscopically, six of the seven lesions were found to be of the protruding type, while the other one was an ulcerating tumor. RESULTS: In all seven cases, the carcinomatous component consisted of differentiated squamous cell carcinoma, and the sarcomatous component was spindle cell carcinoma. Histological analyses demonstrated that the majority of the protruding tumors consisted of the sarcomatous component, while the ulcerating tumor mainly consisted of squamous cell carcinoma. The Ki-67 (MIB-1) labeling index (LI) of the carcinomatous component (28.2%) did not differ significantly from that of the sarcomatous component (25.5%). The sarcomatous component showed abundant expression of type IV collagen and laminin. CONCLUSIONS: It is conceivable that the carcinomatous and sarcomatous components grow separately from the early stage of the tumors, and that the sarcomatous component forms a protruding tumor mass because it has abundant stroma positive for type IV collagen and laminin.

Aged↗
PubMed2000

Superiority of a new UICC-TNM staging system for gastric carcinoma.

BACKGROUND: The definition of the degree of lymph node metastasis (n-classification) for gastric cancer differs greatly in the new Union Internationale Contre le Cancer--TNM classification (5th edition) and the Japanese gastric cancer classification (JGC). The feasibility of the new TNM classification is evaluated in comparison with the JGC. METHODS: At Chiba University, 940 patients who underwent a gastrectomy were retrospectively classified into appropriate stages with both the TNM and JGC systems, and the survival curves of the respective stages were also compared. RESULTS: Patients with 1 to 6 metastatic nodes (TNM-pN1) showed similar survival rates whether the metastases were limited to the perigastric area (JGC-n1) or reached distant areas (JGC-n2). The patients with node metastasis that was limited to the perigastric area (JGC-n1) had significantly different survival rates, depending on the number of metastatic nodes (TNM-pN1 or pN2, P = .022). A similar phenomenon was also observed in patients with TNM-N2 and JGC-n2. A multivariate analysis indicated the TNM N-classification, rather than the JGC n-classification, as an independent prognostic factor. CONCLUSIONS: The new TNM classification appears to be a better prognostic indicator than the JGC system for patients with gastric carcinoma.

Female↗
PubMed2000

Intrahepatic inflow areas of the drainage vein of the gallbladder: analysis by angio-CT.

BACKGROUND: The drainage veins of the gallbladder (cystic veins) are important hepatic metastatic routes of gallbladder cancer. We studied the cystic vein inflow portions of the intrahepatic vessels by computed tomography during angiography (angio-CT). METHODS: The subjects were 27 unoperated pancreatic-biliary patients. After superselective catheterization of the cystic artery, angio-CT was performed, and cystic veins and sinusoidal filling were visualized. We identified the cystic vein inflow routes and the vessels they fed. RESULTS: We found 72 cystic veins in 26 patients. All cystic veins flowed into the intrahepatic portal branches or sinusoids. The cystic veins took either of two routes: one into the liver through the hepatic hilum (17 patients, 21 veins), taken mainly by the portal branch for subsegment 4a (P4a), the anterior portal branch, and the umbilical portion of the portal branch; and the other through the hepatic bed (23 patients, 51 veins), taken mainly by S4a sinusoid, S5 sinusoid, P4a, and P5. CONCLUSIONS: Angio-CT is useful for detecting the cystic vein inflow portions of the intrahepatic vessels. It makes possible identification of areas where there is a possibility for micrometastasis of the gallbladder cancer.

Adult↗
PubMed2000

Clinical benefits of steroid therapy on surgical stress in patients with esophageal cancer.

BACKGROUND: Despite improvements in surgical techniques and perioperative care, severe complications lead to long hospital stays for some esophageal cancer patients. The purpose of this study was to evaluate the safety and effectiveness of perioperative steroid therapy on the postoperative clinical course. METHODS: Fifty-seven patients operated for esophageal cancer in 1997 and 1998 were treated with perioperative steroid therapy. Fifty consecutive patients operated in 1995 and 1996 served as a control group. In the steroid group, each patient was given 250 mg of methylprednisolone intravenously before operation followed by 125 mg on postoperative days 1 and 2. Serum interleukin-6, polymorphonuclear cell elastase, and C-reactive protein levels, and the postoperative clinical course were compared between the groups. RESULTS: Morbidity rates including hyperbilirubinemia, anastomotic leakage, and liver dysfunction were significantly lower in the steroid group than in the control group. Days until extubation and hospital stay were significantly shorter for the steroid group. Inflammatory mediators, body temperature, heart rate, and respiratory index after the surgical procedure were significantly lower in the steroid group. Adverse effects possibly caused by steroid therapy were not observed. CONCLUSIONS: Perioperative steroid therapy was safe and effective for the inhibition of inflammatory mediators and the improvement of the postoperative clinical course of patients with esophageal cancer.

Acute-Phase Proteins↗
PubMed2000

X-ray crystal structure and catalytic properties of Thr252Ile mutant of cytochrome P450cam: roles of Thr252 and water in the active center.

The structure-function relationship in cytochrome P450cam monooxygenase was studied by employing its active site mutant Thr252Ile. X-ray crystallographic analyses of the ferric d-camphor-bound form of the mutant revealed that the mutation caused a structural change in the active site giving an enlarged oxygen-binding pocket that did not contain any hydrophilic group such as the OH group of Thr and H(2)O. The enzyme showed a low monooxygenase activity of ca. 1/10 of the activity of the wild-type enzyme. Kinetic analyses of each catalytic step revealed that the rate of proton-coupled reduction of the oxygenated intermediate of the enzyme, a ternary complex of dioxygen and d-camphor with the ferrous enzyme, decreased to about 1/30 of that of the wild-type enzyme, while the rates of other catalytic steps including the reduction of the ferric d-camphor-bound form by reduced putidaredoxin did not change significantly. These results indicated that a hydrophilic group(s) such as water and/or hydroxyl group in the active site is prerequisite to a proton supply for the reduction of the oxygenated intermediate, thereby giving support for the operation of a proton transfer network composed of Thr252, Asp251, and two other amino acids and water proposed by previous investigators.

Binding Sites↗
PubMed2000

A cysteine protease from maize isolated in a complex with cystatin.

We recently purified a latent but SDS-activated protease complex (40, 15- or 13-kDa proteins) from maize [Yamada et al. (1998) Plant Cell Physiol. 39: 106]. Here, we revealed that the complex was composed of a cysteine protease (40 kDa) and a cystatin, cysteine protease inhibitor (15- or 13-kDa). This is the first report on the isolation of a complex consisting of a cystatin and a target cysteine protease from plants. Cloning of the cysteine protease revealed that it had low homology (25-30%) to other maize cysteine proteases cloned to date but was highly homologous to other plant cysteine proteases such as rice oryzain alpha (84%) and the homologs (50-80%). The cysteine protease expressed in Escherichia coli showed the same substrate and inhibitor specificities as the protease of the complex, demonstrating that the isolated cDNA clone exactly encodes the protease of the complex. The protease expressed in E. coli itself was active but not latent, probably because it was not bound to cystatin. It is most likely that in vitro activation of the protease complex by SDS is caused by the release of bound cystatin. The mRNA of protease was expressed in various tissues except for seeds.

Amino Acid Sequence↗
PubMed2000

Overexpression, enzymatic properties and tissue localization of a ferrochelatase of cucumber.

Ferrochelatase catalyzes the insertion of Fe2+ into protoporphyrin IX to generate protoheme. A putative mature region of a cucumber ferrochelatase cDNA (hemH) was overexpressed in Escherichia coli and purified to homogeneity (40 kDa). The optimum pH was 7.7, and the apparent K(m) values for deuteroporphyrin IX and Fe2+ were 14.4 microM and 4.7 microM, respectively. The activity of the ferrochelatase was inhibited by N-methylprotoporphyrin IX (I50 = 4 nM). Western blot analysis with a polyclonal antibody raised against the recombinant ferrochelatase showed that the antibody crossreacted with protein extracts from hypocotyls and roots of cucumber but not with that from cotyledons. The antibody did not crossreact with proteins of thylakoid membranes of chloroplasts in cucumber cotyledons, although the ferrochelatase activity was mainly associated with the thylakoid membranes. Northern blot analysis also indicated that the hemH gene was expressed mainly in hypocotyls and roots, but little in cotyledons, and the level of the hemH transcripts was not light-responsive. These results demonstrated that the cucumber hemH gene encodes a ferrochelatase which presumably functions for heme biosynthesis in non-photosynthetic tissues, such as hypocotyls and roots, and suggested the presence of other types of ferrochelatase in cucumber, one of which is located in thylakoid membranes of chloroplasts.

Animals↗
PubMed2000

Acute, nontoxic cadmium exposure inhibits pancreatic protease activities in the mouse.

Toxic effects of cadmium on liver, kidney, lung, and testes have been well established in experimental animals and in cell model systems. However, little is known about the effect of cadmium on pancreas, though the pancreas has been reported to accumulate high concentrations of cadmium. Therefore, in this study we examined the effects of cadmium on the pancreas of mice. A single sc injection of 1 mg Cd/kg to mice had no obvious toxic effects on the liver, kidney, and pancreas at both 1 and 5 days after cadmium treatment. Within the pancreas, however, the activities of trypsin, chymotrypsin, and carboxypeptidase A were significantly decreased at 1 day after cadmium treatment, whereas the activity of carboxypeptidase B was not changed. All pancreatic enzyme activities returned to the control levels by 5 days after cadmium treatment. The concentrations of cadmium in pancreas were very similar at 1 and 5 days after cadmium treatment, indicating a stable deposition of the metal. The concentration of zinc in pancreas was markedly increased at 5 days after cadmium treatment. In order to more fully examine the inhibitory effects of cadmium on these protease activities in pancreas, the direct effects of cadmium on purified proteases were studied in vitro. Contrary to the results in vivo, cadmium increased the activity of purified trypsin in a concentration-dependent manner. Consistent with the in vivo results, the activity of purified carboxypeptidase A was decreased by cadmium treatment in a concentration-dependent fashion in vitro. The activities of chymotrypsin and carboxypeptidase B did not change by the cadmium exposure in vitro. The enhanced activity of trypsin by cadmium was returned to the control levels by subsequent treatment with EDTA, indicating that enhancement was reversible. In addition, the zinc normally contained in purified carboxypeptidase A and carboxypeptidase B was released by the cadmium treatment. These results indicate that cadmium inhibits protease activities within the pancreas in vivo at doses that do not induce overt hepatic, renal, or pancreatic toxicity. Based on in vitro study, the decreases seen in trypsin and chymotrypsin activities might be based on indirect effects of cadmium, whereas the decreases in carboxypeptidase A are probably due to the direct inhibition by the metal.

Alanine Transaminase↗
PubMed2000

Hematin polymerization assay as a high-throughput screen for identification of new antimalarial pharmacophores.

Hematin polymerization is a parasite-specific process that enables the detoxification of heme following its release in the lysosomal digestive vacuole during hemoglobin degradation, and represents both an essential and a unique pharmacological drug target. We have developed a high-throughput in vitro microassay of hematin polymerization based on the detection of (14)C-labeled hematin incorporated into polymeric hemozoin (malaria pigment). The assay uses 96-well filtration microplates and requires 12 h and a Wallac 1450 MicroBeta liquid scintillation counter. The robustness of the assay allowed the rapid screening and evaluation of more than 100, 000 compounds. Random screening was complemented by the development of a pharmacophore hypothesis using the "Catalyst" program and a large amount of data available on the inhibitory activity of a large library of 4-aminoquinolines. Using these methods, we identified "hit" compounds belonging to several chemical structural classes that had potential antimalarial activity. Follow-up evaluation of the antimalarial activity of these compounds in culture and in the Plasmodium berghei murine model further identified compounds with actual antimalarial activity. Of particular interest was a triarylcarbinol (Ro 06-9075) and a related benzophenone (Ro 22-8014) that showed oral activity in the murine model. These compounds are chemically accessible and could form the basis of a new antimalarial medicinal chemistry program.

Animals↗
PubMed2000

Two-step selective clamping of IVC for removal of hepatocellular carcinoma with intracaval extension.

Hepatocellular carcinoma (HCC) with retrohepatic intracaval extensions are difficult to treat. HCC may sometimes extend into the inferior vena cava (IVC) through two routes: via the right hepatic vein and via the inferior right hepatic vein. In such cases, in which tumor emboli are located both above and below the confluence of the hepatic vein with the IVC, we first remove the upper embolus during THVE, and then remove the lower one while the IVC is clamped obliquely in order to preserve the residual liver circulation.

Carcinoma, Hepatocellular↗
PubMed2000

Occurrence of IgE antibody-recognizing N-linked glycan moiety of a soybean allergen, Gly m Bd 28K.

BACKGROUND: It has been reported that N-linked glycan moieties of glycoproteins function as IgE-reactive determinants. Gly m Bd 28K, a soybean allergen, was a glycoprotein with glycan moieties, which are supposed to be the Man(3)GlcNAc(2) backbone with the beta1-->2 xylose and alpha1-->3 fucose branches. The purpose of the present study was to examine the IgE-binding ability of the glycan moiety of Gly m Bd 28K in the binding reaction with patients' sera. METHODS: A peptide containing the glycan moiety was prepared from Gly m Bd 28K by digestion with lysyl endopeptidase. The binding site of the glycan moiety was determined by amino acid sequence analyses. The glycan moiety of the allergen was characterized using anti-horseradish peroxidase antibody (anti-HRP) recognizing the N-linked glycan moieties of glycoproteins. The binding of patients' IgE antibodies with their glycan moiety was examined by an immunostaining technique using the glycopeptide and its deglycosylated peptide derived from Gly m Bd 28K. RESULTS: The binding site of the glycan moiety in Gly m Bd 28K was shown to be its Asn20 residue. Gly m Bd 28K did react with anti-HRP and the sera of soybean-sensitive patients, but the binding of IgE antibodies was inhibited by the preincubation with anti-HRP. Moreover, the glycopeptide also reacted with the sera of soybean-sensitive patients, but its deglycosylated peptide did not react with any IgE antibodies of patients' sera. CONCLUSIONS: The specific IgE antibodies recognizing the N-linked glycan moieties of Gly m Bd 28K and other glycoproteins with homologous glycan moieties occur in the sera of soybean-sensitive patients. It was indicated that the N-linked glycan moieties such as that of Gly m Bd 28K may be one of the common IgE-reactive determinants distributed in various plant food proteins.

Allergens↗
PubMed2000

Decreased bilirubin-binding capacity in uremic serum caused by an accumulation of furan dicarboxylic acid.

In chronic renal failure, substances that are effectively excreted in healthy subjects accumulate in serum. These substances, uremic toxins, include a variety of organic acids. It has been reported that a decrease in the bilirubin (BR) binding capacity occurs in the serum of renal failure patients. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has a high affinity for human serum albumin (HSA) and is a potent inhibitor of the serum protein binding of many drugs. We recently reported that CMPF and BR share the binding site for dicarboxylate molecules on the HSA molecule [Pharm Res 1999;16:916-923]. In this study, in order to confirm whether CMPF is involved in the decrease of BR serum binding capacity in chronic renal failure patients, the total concentrations of uremic toxins, CMPF, and indoxyl sulfate (IS) and the free BR concentration in serum from healthy volunteers and renal failure patients were determined. Both total CMPF and IS concentrations correlate with the free BR concentration. However, results from the peroxidase method reveal that IS cannot displace BR under the physiological condition [IS]/[HSA] <1. We, therefore, conclude that CMPF is one of the substances which contribute to the decreased binding capacity of BR in uremic serum.

Adult↗
PubMed2000

Biologic variables in the outcome of stages I and II neuroblastoma treated with surgery as primary therapy: a children's cancer group study.

PURPOSE: To determine prospectively whether surgery alone is sufficient therapy for Evans stages I and II neuroblastoma and to define biologic and clinical features having prognostic potential for this group. PATIENTS AND METHODS: Between June 1989 and August 1995, 374 eligible children (age range, 0 to 18 years) with newly diagnosed stage I (n = 141) and stage II (n = 233) neuroblastoma were registered onto Children's Cancer Group trial 3881. Surgical resection was the only primary therapy except in cases with spinal cord compression, where radiation therapy was allowed. Event-free survival (EFS) and overall survival (OS) were analyzed by life-table methods according to clinical and biologic features. RESULTS: EFS and OS (mean +/- SE) for all stage I patients were 93% +/- 3.0% and 99% +/- 1.0%, respectively, compared with 81% +/- 4.0% and 98% +/- 2. 0%, respectively, for stage II patients. The significantly higher recurrence rate among stage II patients was managed successfully in 38 of 43 children with either surgery or multimodality treatment. There was one death among stage I patients and six among stage II. For stage II patients tumor MYCN gene amplication, unfavorable histopathology, an age greater than 2 years, and positive lymph nodes predicted a lower OS (P <.05). CONCLUSION: Children with stages I and II neuroblastoma have 98% survival with surgery alone as primary therapy. Supplemental treatment was necessary in only 10% of stage I patients and 20% of stage II patients. In children with localized neuroblastoma, a subset of patients that are at higher risk for death can be defined as those with stage II disease who have tumor MYCN amplification or who are >/= 2 years of age with either unfavorable histopathology or positive lymph nodes.

Adolescent↗
PubMed2000

Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children's Cancer Group study.

PURPOSE: Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy. PATIENTS AND METHODS: Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined. RESULTS: Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P =.005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age </= 3 months at diagnosis was significant for EFS (P =. 043), it was less significant for survival (P =.077). The only other significant factor predictive for improved survival was favorable Shimada histopathologic classification. Sites of metastatic involvement (liver, skin, or bone marrow) and surgical resection of the primary tumor were not significant for survival. CONCLUSION: This study confirms the favorable biologic features and excellent survival of infants with stage IV-S neuroblastoma with minimal therapy. Infants younger than 2 months old at diagnosis with rapidly progressive abdominal disease may benefit from earlier and more intensive treatment.

Adrenal Gland Neoplasms↗
PubMed2000

Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group study.

PURPOSE: A prospective Children's Cancer Group study, CCG-3881, has been completed to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NBL) who require differing intensities of treatment. PATIENTS AND METHODS: One hundred thirty-four infants were registered from June 1989 to August 1995, with a median follow-up of 47.1 months (range, 0 to 88 months). The biologic factors examined were tumor MYCN copy number, Shimada histopathologic classification, serum ferritin, and bone marrow immunocytology (sensitivity, one tumor cell per 10(5) bone marrow cells). Patients treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 months (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequent infants with tumor MYCN amplification (n = 18) were transferred after one cycle of therapy to the high-risk CCG-3891 protocol (open January 1991 to April 1996) for more intensive treatment. RESULTS: The 3-year event-free survival (EFS) and overall survival (mean +/- SD) for the 134 infants were 63% +/- 5% and 71% +/- 5%, respectively. Patients whose tumors were without MYCN amplification had a 93% +/- 4% 3-year EFS, whereas those with amplified MYCN had a 10% +/- 7% 3-year EFS (P <. 0001). Each of the other biologic features studied had prognostic significance in univariate analysis but not after stratifying by MYCN copy number. CONCLUSION: Infants less than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children >/= 1 year of age. Nonamplified MYCN tumors identify a group of infants with a 93% +/- 4% EFS, whereas amplified MYCN copy number clearly identifies patients who are unlikely to survive despite intensive chemotherapy.

Biological Factors↗
PubMed2000

Reaction of various lectins to mucin derived from the different layers of rat gastric mucosa: comparison of enzyme-linked lectin binding assay with lectin histochemistry.

The purpose of this study was to demonstrate that the histochemical staining reactivities of lectins in rat stomach actually represent the gastric mucins, and to estimate the utility of the lectins for mucin histochemistry. In this paper, the lectin histochemistry was compared with an enzyme-linked lectin binding assay (ELLA) of the mucins derived from distinct regions and layers of the Sprague-Dawley rat stomach and it was examined to determine the definite binding and problematic binding of the conventional lectin. Among the 10 different biotinylated lectins, Canavalia ensiformis (ConA), Griffonia simplicifolia II (GS-II), Triticuin vulgaris (WGA), Ricinus communis I (RCA-I), Arachis hypogaea (PNA), Glycine max (SBA), Dolichos biflorus (DBA), Ulex europaeus I (UEA-I), Sambucus nigra (SNA) and Maackia amurensis II (MAL-II), examined in this study, GS-II, SBA, DBA, UEA-I, SNA and MAL-II bound clearly to the mucin of distinct regions and layers of the Sprague-Dawley rat stomach in agreement with the results of ELLA. Namely GS-II lectins preferentially bound to the mucin in the mucous neck cells of the corpus area. SBA and DBA clearly recognized the mucin in the covering epithelial mucous cells in the corpus and antral area. UEA-I was widely bound to all the mucin present in both the corpus and antrum. On the other hand, SNA and MAL-II could not react with the mucin obtained from the gastric mucosa but was specifically bound to the mucin purified from the mucous gel layer. These results suggested that the lectins described above are useful histochemical tools to recognize the mucus present in the different regions and layers of Sprague-Dawley rat gastric mucosa.

Animals↗
PubMed2000

Clastogenicity of quinoline derivatives tested by micronucleus induction in vivo in the hepatocytes of partially hepatectomized mice.

The induction of micronucleated liver cells (MN-liver cell) was examined with halogenated and hydroxylated quinolines using partially hepatectomized mice. Among the chloroquinolines, 8-chloroquinoline demonstrated a significantly higher level of induction than the control. All the fluorinated derivatives examined, except for 6-fluoroquinoline, induced significantly higher levels, and there were no appreciable differences in MN-liver cell induction among the fluorinated quinolines, regardless of their mutagenic potencies in the Ames test. Of the hydroxylated quinolines examined, 2- and 4-isomers, which are not mutagenic, induced MN-liver cells to the same extent as a mutagenic isomer, 8-hydroxyquinoline. It seems that clastogenicity was not satisfactorily correlated with mutagenicity in the Ames test as far as this class of compounds is concerned.

Animals↗