Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 181 records · Page 10Linked to original sources

PubMed1992

[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↗

PubMed1992

[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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

Systematization of clinical management for recurrent aborters by combined immunological testing.

The natural outcomes of successive new pregnancies of 66 recurrent aborters were analysed in relation to their immunological profiles. The data demonstrated that the presence of anti-phospholipid antibodies (success rate 6.7%), positive anti-paternal cytotoxicity (8.7%) and a negative mixed lymphocyte reaction (MLR)-blocking effect (33.3%) in the patients' sera were factors associated with a poor prognosis. By the combined evaluation of these testings, a rational scheme of clinical management for recurrent aborters was established.

Abortion, Habitual↗

PubMed1991

Ultrasonographic findings and management of intrahepatic biliary tract abnormalities after portoenterostomy.

Ultrasonographic examinations was made in 24 children who had undergone a portenterostomy to correct extrahepatic biliary atresia. Abnormalities were observed in six patients. These were the result of ongoing inflammatory reactions because all had been suffering from cholangitis after surgery, and the size of the biliary tract structure changed in accordance with the occurrence and subsidence of the cholangitis. Ultrasonographic examination showed dilation of the intrahepatic bile duct in one patient and cystic lesions in five patients. Treatment included percutaneous transhepatic bile drainage for dilated bile ducts, alcohol injections for intrahepatic cysts, and reoperation for cysts in the porta hepatis. Treatment was not required for cysts in controllable cholangitis. The results of these approaches were excellent, indicating that they were of benefit in treatment intrahepatic abnormalities occurring after portoenterostomy.

Bile Ducts, Intrahepatic↗

PubMed1991

Influence of immunotherapy on the cellular immunity of unexplained recurrent aborters.

Changes in lymphocyte subsets in whole blood were analyzed sequentially by flow cytometry with an automated leukocyte differential system in 15 patients with unexplained recurrent spontaneous abortions, each of whom underwent vaccination(s) with her husband's lymphocytes. Mitogen responses of peripheral blood lymphocytes (PBL) were also examined in these patients. The reactivity of PBL against mitogens revealed no significant change in each patient before and after vaccination(s) with her husband's lymphocytes. The CD4:8 ratio was observed to decrease significantly during 22 and 28 days after the first vaccination with a significant increase in the percentage of T suppressor-cytotoxic (CD8) cells. This change was also observed after the second vaccination. The percentages of other subsets did not change significantly after vaccination(s). In 11 patients out of 15, the pregnancy continued successfully and correlated with a predominance of Ts/c (CD8) over TH/I (CD4) cells in the first trimester. These changes in lymphocyte subsets may indicate the induction of immune enhancing mechanisms and it is suggested that continuation of the predominance of Ts/c cells induced by immunotherapy might be important for the successful maintenance of pregnancy.

Abortion, Habitual↗

PubMed1991

A new lymphocyte serotyping using cytotoxic antibodies from secondary recurrent aborters and its application in cases of recurrent abortion and infertility.

Using nonanti-human lymphocyte antigen (HLA) lymphocytotoxic antibodies derived from women with an abnormal pregnancy history including secondary recurrent abortion, a new series of serotyping was performed on lymphocytes from 37 couples (74 individuals), and the compatibility between the couples shown by the typing was investigated. The data demonstrated that both couples with primary recurrent abortion and infertile couples with repeated failure of embryo transfers after in vitro fertilization showed significantly close reaction patterns between partners than normal child-bearing couples by principal component factor analysis. It was concluded that this serotyping provides useful information on histocompatibility in the field of pregnancy immunology and that some cases of infertility because of implantation failure, as well as primary recurrent abortion, might be caused by underlying immunogenetical problems.

Abortion, Habitual↗

PubMed1991

[Comparative studies on the antitumor activity of fluorinated pyrimidine derivatives against human bladder, cervical and ovarian cancer xenografts in nude mice].

Fluorinated pyrimidines given orally were examined for their antitumor activity with 11 human cancer xenograft models (4 bladder, 4 cervical and 3 ovarian cancers). The drugs were evaluated to be effective when they inhibited tumor growth over 58%. UFT was not effective against all of 11 cancer xenografts tested. 5-Fluorouracil (5-FU) was effective against only one bladder cancer xenograft among 6 cancer xenografts tested. On the other hand, 5'-deoxy-5-fluorouridine (5'-DFUR) was effective against one bladder, 3 cervical and one ovarian cancer xenografts. The Antitumor activity of 5'-DFUR was correlated with the enzyme activity of pyrimidine nucleoside phosphorylase, which is an essential enzyme for phosphorolysis of 5'-DFUR to 5-FU.

Administration, Oral↗

PubMed1991

Relationship between oxidative stress and hepatic phosphoglucomutase activity in rats.

The relationship between the oxidative stress and inactivation of hepatic enzymes was examined in rats. An intake of lipid peroxidation products or pro-oxidative drugs provokes oxidative stress in the living body. Secondary peroxidation products of linoleic acid were administered orally, and the oxidative stress was evaluated by thiobarbituric acid (TBA) and haemoglobin-methylene blue (HMB) tests, and by the reduction in tocopherol level. A specific decrease in hepatic phosphoglucomutase activity was found following the oxidative stress caused by the dose with secondary products. Then, ten pro-oxidative drugs were administered intraperitoneally and the effects on the enzymatic activity were determined. Among the ten drugs, CCl4, alcohol, paraquat, phenobarbital, thiopental and methylcholanthrene caused the TBA values to increase, and the phosphoglucomutase activity to decrease, in the liver 24 h after the doses. It was attempted to clarify the inactivation mechanism by using parenchymal hepatocytes. When the cells were cultured in medium containing aldehydic products originating from lipid peroxidation, these aldehydes significantly suppressed the induction of phosphoglucomutase by dexamethasone as compared with the cells in aldehyde-free medium. We consider that aldehydes inhibit the hormonal induction of phosphoglucomutase in the rat liver.

Administration, Oral↗

PubMed1991

[Epidemiologic and clinicopathologic studies of partial hydatidiform mole].

To determine the epidemiological and clinicopathological characteristics of partial hydatidiform mole (PHM), a comparative study of PHM and complete hydatidiform mole (CHM) was performed in molar patients who were entered in the regional registry of Niigata Prefecture and/or who were admitted for treatment at Niigata University Hospital. The results obtained are as follows. 1. From 1971 to 1988, 2,290 hydatidiform moles (HMs) were documented in the registry. The incidence of HM was annually decreasing with an almost constant ratio to the total number of pregnancies. Since 1986, the number of PHM was rising with an inverse decrease in CHM. One hundred fifty one of 1,923 CHM (7.9%) had persistent trophoblastic disease (PTD), but on the other hand only 6 of 367 cases PHM (1.6%) had. 2. In 275 patients treated in our hospital from 1971 to 1990, 134 of 240 with CHM (55.8%) and 6 of 35 with PHM (17.1%) experienced PTD. Of 6 PTD patients following PHM, 3 had invasive mole, 1 metastatic mole and 2 post molar persistent hCG, but no choriocarcinoma. 3. The recent study of DNA analysis in molar tissue revealed that one case, which had been diagnosed as PHM, coexisted with CHM and non-molar pregnancy.

Adult↗

PubMed1991

[Effects of various growth factors on the proliferation and the differentiation of trophoblastic cells in vitro].

EGF, PDGF, IL-6, TGF-beta 1 and supernatants from decidual cell cultures were added in various concentrations to cultures of normal trophoblastic cells in vitro. Effects on cell proliferation and differentiation were assessed by using 3H-thymidine uptake test and measuring hPL, hCG production in culture media, respectively. EGF stimulated only hPL, hCG production and in contrast, PDGF stimulated 3H-thymidine uptake only. IL-6, TGF-beta 1 and decidual supernatants stimulated both hPL, hCG production and 3H-thymidine uptake, especially TGF-beta 1 and decidual supernatants. These results suggest that EGF is related to the differentiation, PDGF is to the proliferation, and IL-6, TGF-beta 1 and decidual supernatants are to both the differentiation and proliferation of trophoblastic cells. Further understanding of the effects of these products on trophoblastic growth may provide important insights into mechanisms of early pregnancy development.

Cell Differentiation↗

PubMed1991

Hepatic dysfunction caused by dietary products of lipid peroxidation.

Dietary products of lipid peroxidation cause hepatic dysfunctions such as reductions in activities of aldehyde dehydrogenase (mitochondrial NAD-dependent), succinate dehydrogenase, phosphoglucomutase, glucokinase, and glucose-6-phosphate dehydrogenase, and a depletion of coenzyme A. Toxic products in the peroxidation are considered to be the aldehydes among the decomposed products from hydroperoxides, because the decomposed products were incorporated into the liver but the other products were not when they were administered orally to rats. There are three current ideas on the causes of the dysfunctions: (a) direct attack of the incorporated aldehydes on the enzymes, (b) injury of the bio-membranes by the aldehydes, and (c) disturbance of the synthetic system for enzymes. In this study, to examine these ideas, a reasonable concentration of the peroxidation products to use in vitro was estimated from the amounts present in the liver after an oral dose of lipid peroxidation products. With respect to idea (a), when the peroxidation products were added to subcellular fractions of hepatocytes, the decomposed products specifically inactivated aldehyde dehydrogenase and glucose-6-phosphate dehydrogenase, and destroyed coenzyme A. For ideas (b) and (c), in which the parenchymal hepatocytes isolated from rat were used, the decomposed products did not seem to injure the bio-membrane, but they inhibited induction of glucokinase by hormones in the hepatocytes. It was concluded that in the hepatic dysfunction caused by the dietary products of lipid peroxidation the incorporated decomposed products in the liver directly inactivated the mitochondrial NAD-dependent aldehyde dehydrogenase and glucose-6-phosphate dehydrogenase, destroyed coenzyme A, and disturbed the synthetic system of glucokinase.

Animals↗

PubMed1990

[Examination of the effects of age on prognostic factors of squamous cell carcinoma of the uterine cervix].

The presence or absence of an association between age and prognostic factors of squamous cell carcinoma of the uterine cervix, including histologic cell type, depth of invasion, stromal reaction, CPL classification, and lymph node metastasis, was examined in 380 patients who had undergone radical hysterectomy. Age affected the rate of lymph node metastasis according to depth of invasion, and the metastasis rates in patients with invasion of 2/3 of the lateral side of the muscular layer (gamma type) in groups of patients in their 30s, 40s, 50s, and 60s were 40.0% (4/10), 59.3% (16/27), 36.7% (18/49), and 21.6% (8/37), respectively. Similarly, the metastasis rates in patients with invasion of the parametrium (delta type) in the above age groups were 100% (1/1), 72.7% (8/11), 46.4% (13/28), and 36.7% (11/30). Lymph node metastasis was significantly less in patients in their 60s than those in their 40s (gamma: p less than 0.01, delta: p less than 0.05). Moreover, 5-year survival rates of patients with lymph node metastasis (tested by Kaplan-Meier method) were 33.3% (N = 4), 65.0% (N = 15), 81.9% (N = 17), and 100% (N = 8) in groups of patients in their 30s, 40s, 50s, and 60s respectively, in the gamma type, and 45.0% (N = 8), 45.7% (N = 10), and 79.6% (N = 11) in groups of patients in their 40s, 50s, and 60s respectively, in the delta type. A significant difference was noted between the group of patients in their 60s and other age groups (gamma: p less than 0.01, delta: p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Endorectal ultrasonography with a 7.5 MHz linear array scanner for the assessment of invasion of rectal carcinoma.

An endorectal 7.5 MHz linear array scanner was used for the assessment of invasion in rectal tumours. As a preliminary study normal rectal wall of the resected specimen was scanned with the 7.5 MHz linear array scanner. The rectal wall was depicted in seven layers. The anatomical identification of these seven layers was made. Forty nine patients with rectal tumours were examined by endorectal ultrasonography with the 7.5 MHz linear array scanner. The sensitivities for T1, T2 and T3 tumours using the UICC TNM classification were 81%, 100% and 90% respectively, and the specificities were 100%, 85% and 100% respectively. Definite discrimination of lesions confined to the mucosa from those invading submucosa was difficult, even using this kind of high frequency ultrasonography. When the sonographic assessment was mucosal, or mucosal or submucosal involvement, local excision was performed. When the assessment was invasion in the muscularis propria or invasion penetrating the muscularis propria, bowel resection was performed. Except in one case, the histology of the resected specimens of the 49 cases confirmed the adequacy of the operation methods selected. Although there was some difficulty in making the distinction between mucosal and submucosal lesions, endorectal ultrasonography with the 7.5 MHz linear array scanner was considered to provide useful information in deciding on the type of operation offered to the patient.

Carcinoma↗