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Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 19 recordsLinked to original sources

Carbohydrate binding specificity of immobilized Psathyrella velutina lectin.

The carbohydrate binding specificity of Psathyrella velutina lectin (PVL) was thoroughly investigated by analyzing the behavior of various complex-type oligosaccharides and human milk oligosaccharides on a PVL-Affi-Gel 10 column. Basically, the lectin interacts with the nonreducing terminal beta-N-acetylglucosamine residue, but does not show any affinity for the nonreducing terminal N-acetylgalactosamine or N-acetylneuraminic acid residue. Substitution of the terminal N-acetylglucosamine residues of oligosaccharides by galactose completely abolishes their affinity to the column. GlcNAc beta 1----3Gal beta 1----4sorbitol binds to the column, but GlcNAc beta 1----6Gal beta 1----4sorbitol is only retarded in the column. The behavior of degalactosylated N-linked oligosaccharides is quite interesting. Although all degalactosylated monoantennary sugar chain isomers are retarded in the column, those with the GlcNAc beta 1----2Man group interact more strongly with the column than those with the GlcNAc beta 1----4Man group or the GlcNAc beta 1----6Man group. The degalactosylated bi- and triantennary sugar chains bind to the column, but the tetraantennary ones are only retarded in the column. These results indicated that the binding affinity is not simply determined by the number of terminal N-acetylglucosamine residues. Addition of the bisecting N-acetylglucosamine residue reduces the affinity of oligosaccharides to the column, but addition of an alpha-fucosyl residue at the C-6 position of the proximal N-acetylglucosamine residue does not affect the behavior of oligosaccharides in the column. These results indicated that the binding specificity of PVL is quite different from those of other N-acetylglucosamine-binding lectins from higher plants, which interact preferentially with the GlcNAc beta 1----4 residue.

Basidiomycota

Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody.

Seventeen women with recurrent fetal loss associated with anti-phospholipid antibody were treated by prednisolone and low-dose aspirin (PSL/ASP) therapy from the early gestational period. The success rate of pregnancy in the treated patients was significantly higher than that in 12 untreated patients of similar background, including age, number of previous fetal losses and anti-cardiolipin titre (76.5 versus 8.3%, P less than 0.01). The degree of fetal growth retardation evident in previous pregnancies was also improved by the therapy, suggesting that PSL/ASP itself has a beneficial effect against placental damage. These clinical improvements were accompanied by a reduction in anti-phospholipid antibody titre, especially that of anti-phosphatidylserine antibody (anti-PS), to within the normal range within 8 weeks after PSL/ASP administration in most of the treated patients. There was no reduction of antibody titre in the untreated patients during pregnancy. It was concluded that PSL/ASP therapy, when started in the early gestational period (prior to 8 weeks gestation), was effective for the achievement of successful pregnancy and the prevention of fetal growth retardation and that the anti-PS titre was a good clinical marker for evaluating the effect of PSL/ASP therapy.

Abortion, Habitual

Benign follicular thyroid nodule composed of signet-ring-like cells with PAS-negative thyroglobulin accumulation in dilatated rough endoplasmic reticulums.

A benign follicular thyroid nodule composed of signet-ring-like cells in a 46-year-old Japanese euthyroid woman is reported. Thyroglobulin was positive, and periodic acid-Schiff (PAS) and other mucin stainings were negative in the cytoplasm of signet-ring-like cells. Ultrastructurally their cytoplasm contained many dilatated rough endoplasmic reticulums (rERs), the largest of which compressed the nucleus toward the cellular apical portion. Functional disturbance of rER or Golgi apparatus might be the cause of this characteristic cellular change.

Adenocarcinoma, Mucinous

Carbohydrate structures of beta-core fragment of human chorionic gonadotropin isolated from a pregnant individual.

Highly purified beta-core fragment was obtained from urine of a pregnant woman with use of an immunoaffinity column. The amino acid sequence of beta-core fragment indicated that it is composed of two polypeptides linked by a disulfide bond. The two polypeptides correspond to the 6-40 and 55-92 portions of hCG beta-subunit. Both Asn13 and Asn30 residues were glycosylated. The N-linked sugar chains of beta-core fragment were quantitatively released as radioactive oligosaccharides by hydrazinolysis, followed by N-acetylation and NaB3H4 reduction. The radioactive oligosaccharides were fractionated by serial lectin column chromatography and Bio-Gel P-4 column chromatography, and their structures were investigated by sequential exoglycosidase digestion and periodate oxidation. The results indicated that they were a mixture of the four oligosaccharides: Man alpha 1----6(+/- Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc. The structural characteristics of the sugar chains of beta-core fragment are quite different from those of the beta-subunit of hCG whose structures were typical biantennary sugar chains containing the Neu5Ac alpha 2----3Gal beta 1----4GlcNAc beta 1----2 group as their outer chains.

Amino Acid Sequence

Ultracytochemistry of glucose-6-phosphate dehydrogenase in adrenal gland.

The distribution of glucose-6-phosphate dehydrogenase (G6PD) activity has been studied by a copper ferrocyanide method in the adrenal cortex cells of a rat. The site of the G6PDH activity was close to the ribosome between the round mitochondria of zonas fasciculata and reticularis.

Adrenal Glands

Butylated hydroxyanisole produces both mutagenic and desmutagenic derivatives under gastric conditions.

Dietary butylated hydroxyanisole (BHA) has been known to have inconsistent functions on carcinogenesis, both prevention and initiation. We assumed that both functions of BHA were introduced by the derivatives formed after the reaction with gastric components such as nitrite in the stomach. We then identified the derivatives produced by incubating BHA with sodium nitrite at pH 2.0 or pH 5.0. Eight derivatives were detected; 2-tert.-butyl-p-quinone (BQ), 3,3'-di-tert.-butyl-biphenyldiquinone-(2,5,2',5') (BBDQ), 2,6-di-tert.-butyl-8-hydroxy-dibenzofuran-1,4-quinone (BHDQ), 6-nitro-BHA, 2,2'-dihydroxy-3,3'-di-tert.-butyl-5,5'-dimethoxy-biphenyl (di-BHA), an oxidized product of di-BHA, and two unstable reaction intermediates. BQ was a major final product at pH 2.0, but not at pH 5.0. 6-Nitro-BHA and the oxidized products of di-BHA were also the final products. BBDQ was formed from di-BHA and easily converted to BHDQ. Their mutagenicity and desmutagenicity were assayed using Salmonella typhimurium strains. BQ and BBDQ were the mutagens of base-substitution type, BHDQ was the potent desmutagen against a mutagenicity of Trp-P-2, and the others had neither of the two activities. Thus, BHA was found to produce both the mutagen and desmutagen under the gastric conditions. BQ has been previously reported to be easily detoxified by glutathione, and BHA itself is well known to prevent carcinogenesis. In the assessment of dietary BHA on carcinogenesis, since one of the mutagens from BHA is easily detoxified in our bodies and another is converted to a desmutagen, BHA appears to be one of the favourable chemicals for us.

Anticarcinogenic Agents

Intramedullary spinal cord metastasis from lung cancer presenting with paraparesis: an autopsied case.

A 75-year-old male presented with paraparesis and pain in the thighs, which progressed rapidly. Five days later, he was unable to stand or to void urine. A lung cancer was found in the right upper lobe. A spinal cord metastasis from the lung cancer was suspected from the neurologic and pulmonary findings. After 2 weeks, motor dysfunction and a total sensory deficit were observed below the lumbar region, and the patient developed pneumonia, which resulted in death. Autopsy showed an extensive intramedullary metastasis at the third lumbar segment of the spinal cord. Histology revealed poorly differentiated adenocarcinoma of the lung.

Adenocarcinoma

[Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group].

We evaluated antitumor effect histologically and assayed the tissue levels of 5-fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives.

Chemotherapy, Adjuvant

[The study of ovarian metastasis in uterine cancer].

The correlation between histological ovarian metastasis and histologic cell type, clinical stage, depth of invasion, lymph node metastasis, and menstrual activity were analyzed in 566 patients who underwent surgery for uterine cancer at the hospital of Niigata University between January, 1971 and May, 1990. Ovarian metastasis was studied in 456 patients with stage Ib or more advanced cervical cancer and 110 patients with stage Ia or more advanced endometrial cancer. The following results were obtained: 1. The incidence of ovarian metastasis of cervical cancer by histologic cell type was 18.6% (8/43) for adenocarcinoma, 6.7% (1/15) for mixed type adenocarcinoma and squamous cell carcinoma, and 0% (0/398) for squamous cell carcinoma. The metastasis rate in patients with endometrial carcinoma was 10.8% (10/93) for adenocarcinoma, but there was no metastasis of 2 squamous cell carcinoma, 13 mixed type of adenocarcinoma and squamous cell carcinoma or 2 undifferentiated carcinoma. 2. The incidence of metastasis of cervical adenocarcinoma by stage was 5.3% (1/19) for stage Ib and 29.2% (7/24) for stage II. The metastasis rate of mixed type of adenocarcinoma and squamous cell carcinoma was 0% (0/6) for stage Ib and 11.1% (1/9) for stage II. The incidence of metastasis of endometrial carcinoma was 2.1% (1/47) for stage Ia, 15.0% (3/20) for stage Ib, 15.0% (6/40) for stage II and 0% (0/3) for stage III. 3. All the patients with ovarian metastases of uterine cervical cancer had invasion to a depth of more than 2/3 of the uterine cervix, while the incidence of ovarian metastasis of endometrial carcinoma was increased with deep invasion of the uterine muscular layer, and metastasis was present even in shallow invasion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

In vitro and in vivo antibacterial activities of meropenem, a new carbapenem antibiotic.

The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.

Animals

Age as a prognostic factor in patients with squamous cell carcinoma of the uterine cervix.

Correlations between age and several prognostic factors, such as histologic cell type, depth of invasion, intravascular invasion, and lymph node metastases (LNM), were analyzed in squamous cell carcinoma of the cervix (SCC). A total of 380 patients with Stage IB or more advanced SCC underwent radical hysterectomy at the authors' institution from 1971 to 1987. The cases were divided into four age groups: 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 69 years. The depth of invasion was classified in four categories according to pathologic examination of surgical specimens. The only significant factor was the frequency of LNM with deeper invasion, which was less in the 60-to-69-year age group than in the younger age groups. The 5-year survival rates of the patients with LNM also were higher in the 60-to-69-year group. Thus, age 60 or older can be considered a prognostic factor correlating to LNM in squamous cell carcinoma of the cervix.

Adult

Transmembrane diffusion of hydrophobic antimicrobial agents and cell surface hydrophobicity in Bacteroides fragilis.

The transmembrane diffusion of hydrophobic antimicrobial agents, e.g. lincomycin and clindamycin, was examined in Bacteroides fragilis which is sensitive to these agents. The results showed that these agents penetrate efficiently through the outer membrane. Cell surface hydrophobicity measured by the partition assay between water and p-xylene revealed that the cell surface of B. fragilis is more hydrophobic than that of Salmonella typhimurium or Pseudomonas aeruginosa. Furthermore, treatment with low concentrations of surfactant caused cell lysis. These results suggest that the cell surface hydrophobicity in B. fragilis plays an important role in the efficient transmembrane penetration of hydrophobic compounds. This efficiency explains the susceptibility of B. fragilis to hydrophobic antimicrobial agents.

Anti-Bacterial Agents

Hepatotoxicity caused by dietary secondary products originating from lipid peroxidation.

Hepatic dysfunction caused by oxidative stress when secondary peroxidation products were administered orally was investigated in rat. In serum at 24 hr after the administration of secondary products, the contents of lipid peroxides reached a maximum, the level of tocopherol reached a minimum, and the transaminase activities were elevated. In the liver, the lipid peroxide contents were kept high between 6 and 24 hr and tocopherol level was kept low between 15 and 48 hr after the does. Therefore, the hepatic oxidative stress was most severe around 15 hr after the dose. Dysfunction in the liver having oxidative stress was then made clear. One was a disturbance in synthetic system of glucose 6-phosphate. The decreases in activities of phosphoglucomutase and glucokinase reduced a level of glucose 6-phosphate, which suppressed the supply of NADPH in pentose cycle, while the NADPH was consuming well for detoxification of endogenous lipid peroxides. Another was specific inactivations of mitochondrial succinate dehydrogenase and aldehyde dehydrogenase. A third was the depletion of CoASH, which induced the decreases in activities of citrate cycle and lipogenesis. The other was a formation of lipofuscin. Even after the liver was recovering from the oxidative stress, the liver was getting hypertrophy and lipofuscin was accumulating. To make the cause of hepatic dysfunction clear, it was examined whether the incorporated secondary products in the liver could directly attack the enzymes or not. A reasonable amount of secondary products present in the liver was estimated, and then the amount of secondary products was added in hepatic subcellular organelles in vitro. It was found that mitochondrial NAD-dependent aldehyde dehydrogenase, glucokinase, and CoASH were directly attacked and inactivated by the incorporated secondary products in the liver. Thus, a part of dietary secondary products was incorporated into liver, and was not detoxified, but injured the enzymes and CoASH. Then it resulted in lipofuscin formation.

Administration, Oral

Target enzymes on hepatic dysfunction caused by dietary products of lipid peroxidation.

Dietary products of lipid peroxidation cause hepatic dysfunction due to decreases in the activities of some hepatic enzymes and to depletion of CoA. An idea about the decreases and depletion is that the enzymes and CoA could be injured directly by the incorporated products in the liver. Their inactivations in vitro were then examined using a reasonable amount of peroxidation products. The hepatic cytosol, microsomes, and mitochondria were incubated with 10, 15, and 20 micrograms/mg protein of peroxidation products, respectively, and changes in the enzymatic activities were monitored. Glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, glucokinase, and glyceradehyde phosphate dehydrogenase were inactivated, and the CoA level was decreased, but the other hepatic enzymes were not. Although glyceraldehyde phosphate dehydrogenase was most sensitive to peroxidation products in vitro, the decrease in activity was not detected by the oral dose of secondary products. On the other hand, among the components of peroxidation products, hydroperoxides and polymers are not incorporated in the liver, but decomposed products of low molecular weight are incorporated. Glucokinase among the above enzymes was not inactivated by the low-molecular-weight products. It was therefore concluded that glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, and CoA were targets of the direct attack by incorporated components of peroxidation products in the liver.

Aldehyde Dehydrogenase