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Biomedical subjects

N Toki

Publications and source records attributed to N Toki.

At least 19 recordsLinked to original sources

Enhanced protein levels of protein thiol/disulphide oxidoreductases in placentae from pre-eclamptic subjects.

Recent studies have indicated that pre-eclampsia is closely associated with oxidative stress both in maternal circulation and in the placenta. Protein thiol/disulphide oxidoreductases, such as thioredoxin, glutaredoxin, and protein disulphide isomerase have recently been found to eliminate reactive oxygen species (ROS) and regenerate oxidatively damaged proteins. Protein thiol/disulphide oxidoreductases may also play a role in combating pre-eclampsia. In this study, we examined the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins, which are markers of lipid peroxidation, in human placentae of normal and pre-eclamptic subjects. We also examined the protein levels of thioredoxin, glutaredoxin, and protein disulphide isomerase in placentae. Immunoblotting and immunohistochemistry showed that HNE-modified proteins accumulated to a greater extent in pre-eclamptic placentae than in normal placentae. In both normal and pre-eclamptic placentae, thioredoxin, glutaredoxin, and protein disulphide isomerase were detected in the trophoblasts of the floating villi. The levels of these proteins were increased approximately 2- to 3-fold in the pre-eclamptic placentae compared to the normal placentae. These results indicated that the pre-eclamptic placentae were exposed to oxidative stress and that the protein thiol/disulphide oxidoreductases were adaptively induced in pre-eclamptic placentae, suggesting possible roles for thioredoxin, glutaredoxin, and protein disulphide isomerase in protecting placental functions against oxidative stress caused by pre-eclampsia.

Adult↗

Glassy cell carcinoma of the uterine cervix: combination chemotherapy with paclitaxel and carboplatin in recurrent tumor.

Combination chemotherapy with paclitaxel and carboplatin every 4 weeks for 3 cycles was administered for recurrent glassy cell carcinoma of the uterine cervix in a 67-year-old Japanese female. The response rate was 56% under computed tomography (partial response). However, the effect was transient even with follow-up radiotherapy, and further cases need to be accumulated to determine a successful treatment modality.

Aged↗

Localization of thioredoxin reductase and thioredoxin in normal human placenta and their protective effect against oxidative stress.

Recent studies have indicated that oxidative stress is involved in the pathogenesis of pre-eclampsia. Oxidative stress damages systemic tissues, and placental damage may result in intrauterine growth retardation and fetal distress. Thus, this study attempted to elucidate the placental localization of thioredoxin and thioredoxin reductase, substances that may reduce oxidative stress. Furthermore, it studied the defence mechanism of the thioredoxin-thioredoxin reductase system against oxidative stress in mitochondria of normal human placenta where reactive oxygen species are primarily produced. The examination of thioredoxin reductase activity in subcellular fractions of human placenta indicated that thioredoxin reductase was located not only in cytoplasm, but also in mitochondria. The existence of thioredoxin and thioredoxin reductase in human placenta was confirmed immunologically using antibodies raised against thioredoxin and thioredoxin reductase. Thioredoxin and thioredoxin reductase were localized histochemically in cytotrophoblasts, decidua, and stromal cells in the stem villi. The addition of exogenous thioredoxin and thioredoxin reductase to fumarase in mitochondria of human placenta displayed a protective effect against oxidative stress. In conclusion, this study confirmed the intracellular localization and the tissue distribution of thioredoxin and thioredoxin reductase in human placenta. Moreover, the complete thioredoxin-thioredoxin reductase system in human placenta may protect the placenta from damage caused by oxidative stress.

Blotting, Western↗

The significance of peritoneal cytology in uterine cervix and endometrial cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer. MATERIALS AND METHODS: The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan-Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor. RESULTS: The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.

Endometrial Neoplasms↗

Immunohistochemical distribution of surfactant apoproteins in hypoplastic lungs of nonimmunologic hydrops fetalis.

Forty-three patients with nonimmunologic hydrops fetalis (NIHF), including 32 patients (74%) with hypoplastic lung, were immunohistochemically examined for the expression of surfactant apolipoproteins (SPs), using anti-gamma G immunoglobulins against human SP-A with a molecular weight (MW) of 35 K and SP-B with a MW of 5 K compared with that in 59 patients in a control group and 45 patients with hypoplastic lung induced by causes other than NIHF. In the control group, SP-A was expressed in the lungs from 23 gestational weeks and became more numerous and intense in alveolar type II cells after 31 gestational weeks, whereas SP-B began to be expressed from 20 gestational weeks, and almost all patients showed a diffuse positivity after 26 gestational weeks. In the NIHF group, SP-A expression was generally weak, even after 31 gestation weeks. Moreover, most of the patients showing a weak expression of SP-A were also associated with hypoplastic lung and had a clinical history of persistent intrauterine pleural effusion of more than 2 weeks. Conversely, the immunoreactivity of SP-B was well preserved in NIHF cases either with or without hypoplastic lung. These results suggest that in the NIHF lung, there is a possible delay in the functional maturation or development of SP-A synthesis by alveolar type II cells, and this retardation of the functional maturation in type II cells also participates in the postnatal respiratory insufficiency in NIHF.

Antibodies, Monoclonal↗

An immunohistochemical study of the expression of surfactant apoprotein in the hypoplastic lung of rabbit fetuses induced by oligohydramnios.

We shunted amniotic fluid from alternate gestational sacs into the maternal peritoneal cavity between 23 and 30 days gestation in fetal rabbits (full term, 31 days) to investigate the effect of oligohydramnios on surfactant apoprotein A (SP-A) expression by an immunohistochemical morphometric analysis. The amniotic shunt produced a significant decrease in the amniotic fluid volume (P < 0.02), as well as a reduction in the lung weight (P < 0.005) and lung/body weight ratio (P < 0.001), which indicated lung hypoplasia. These fetuses also showed a statistically significant reduction of SP-A expression, ie, SP-A-positive type II cells per unit area (P < 0.05), SP-A-positive type II cells/total cells ratio (P < 0.001), the percentage of SP-A-positive area per unit area (P < 0.005), and the SP-A-positive area/alveolar epithelium area plus the lung interstitium area ratio (P < 0.005). These results suggest that oligohydramnios significantly retards and modifies the structural growth and functional development of alveolar type II cells in SP-A expression. This animal model of hypoplastic lung in fetuses is thus considered to be useful in helping to further develop the treatment for hypoplastic lung.

Animals↗

[Problems in Papanicolaou classification].

There are several reasons why Papanicolaou classification should not be used for the interpretation of cytologic findings. First, many different classification criteria are sometimes used for a single pathologic condition. Second, inflammatory change or hormonal evaluation are not included in the system. Third, the classification is not compatible for the evaluation of endometrial lesions or chorionic diseases. Fourth, mismanagement of the patient is sometimes encountered when this classification is only used. Instead of Papanicolaou classification, descriptive diagnosis should be used for cytologic interpretation.

Aged↗

Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy.

The polymerase chain reaction (PCR) method was used to determine the presence and amount of human T lymphotropic virus type I (HTLV-I) proviral DNA in central nervous system (CNS) tissue obtained at autopsy from 6 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 1 patient with adult T-cell leukemia (ATL) and CNS infiltration of leukemic cells, and 9 control subjects with other neurological disorders. HTLV-I pX and env but not pol DNA were detected in CNS tissue from 5 of 6 patients with HAM/TSP. The ATL samples were positive for pX, env, and pol DNA by PCR. None of the control samples was consistently positive for HTLV-I by PCR, but all showed positive bands on beta-globin PCR. Quantitative PCR combined with histological studies showed no correlation between HTLV-I proviral DNA amounts and extent of perivascular mononuclear cell infiltration in the HAM/TSP CNS. Also, the amounts of pX and probably env DNA were greater in the HAM/TSP samples than in the ATL sample, although the extent of mononuclear cell infiltration was far less in the HAM/TSP samples than in the ATL sample. Therefore, in addition to infiltrating mononuclear cells, constituent cells of the CNS may harbor the HTLV-I genome, at least in the pX and env regions, in patients with HAM/TSP.

Base Sequence↗

[An autopsy case of citrullinemia type II complicated with chronic pancreatitis].

A 34-year-old woman had developed frequent episodes of disorientation at night since a year ago. Her blood ammonia level was found to be markedly increased. Serum amino acid pattern and biochemical analysis of urea cycle enzymes in the liver indicated type II citrullinemia. Pancreatolithiasis was found by ultrasonography and CT scan. After a short remission following treatment by protein restriction and oral administration of sodium benzoate, she had disturbed consciousness due to exaggerated hyperammonemia and died of severe brain edema. In this report, efficacy of the treatment for hyperammonemia and histopathological findings are discussed.

Adult↗

Microscopic ovarian metastasis of the uterine cervical cancer.

Six hundred forty-seven cases of carcinoma of the uterine cervix with FIGO stages Ib or more were initially treated with hysterectomy at Kyushu University Hospital from 1973 to 1987. In these, 597 cases could be pathologically reviewed for ovarian metastasis. In these 597 cases, 335 were stage Ib, 71 IIa, 185 IIb, and 6 IIIb. Only 3 (0.5%) of 597 showed ovarian metastasis. All 3 cases were stage IIb. None of stage Ib cancer cases had ovarian metastasis. One (0.19%) of 524 squamous cell carcinomas metastasized to the ovary, whereas 2 (5.5%) of 36 pure adenocarcinomas revealed ovarian metastasis. Interestingly, all ovarian metastatic lesions were microscopic in size and found in the ovarian hilus. As for the primary lesion, all cases with ovarian metastasis showed deep myometrial invasion, corpus invasion, and lymphatic permeation. Two cases showed pelvic lymph node metastases and positive peritoneal washing cytology. From the results of our study, it can be said that it is fairly safe to preserve the ovary at the time of radical operation in squamous cell carcinoma of the uterine cervix, but it may not be safe to preserve the ovary in pure adenocarcinoma of the uterine cervix.

Adenocarcinoma↗

Distribution of basement membrane antigens in the uterine cervical adenocarcinomas: an immunohistochemical study.

The distribution of laminin and collagen type IV in the basement membrane of 45 uterine cervical adenocarcinomas was studied using immunohistochemical techniques. Staining patterns of basement membranes were divided into three types, according to the intensity of staining: thick and discontinuous (type I), thin and discontinuous (type II), and fragmentary (type III). In well-differentiated adenocarcinomas, 17 of 24 cases (71%) showed type I and the remaining 7 showed type II. In contrast, in poorly differentiated adenocarcinomas 4 of 5 cases (80%) showed type III. Five of six cases (83%) of adenoma malignum, even though extremely well differentiated, showed type III. Staining patterns of the basement membranes correlated with histological grade. Five-year survival rate of patients with type I and II staining (74%) was better than that of patients with type III (55%).

Adenocarcinoma↗

[Seven cases of primary adenocarcinoma of the fallopian tube].

Seven patients with primary adenocarcinoma of the fallopian tube were treated at Kyushu University Hospital from 1978 to 1987. They were 0.59% of all patients with gynecologic malignancies in our hospital. Their mean age was 56.0 years old. Four of 7 patients presented with abnormal genital bleeding. Pelvic mass was detected in 6 of 7 patients. One patient showed abnormal cervical cytology and 3 of 6 patients had positive endometrial cytology and/or histology. No diagnosis of tubal cancer was made preoperatively. Primary surgical treatments were performed in all patients. Four patients, who underwent dissection and/or biopsy of pelvic and paraaortic lymph nodes, had no metastasis. However, at the time of recurrence, paraaortic and/or neck lymph nodes metastases were present in 3 of 4 patients. Following surgery, combination chemotherapy with cyclophosphamide, doxorubicin and cisplatin (CAP) was administered to 6 of 7 patients. Partial responses were obtained in 2 patients with recurrent and evaluable lesions. The mean survival time of 7 patients as yet was 36.0 months after diagnosis. In conclusion, the difficulty of preoperative diagnosis of tubal cancer was reconfirmed. CAP combination chemotherapy seemed to be effective for the treatment of tubal cancer and further study with more cases is warranted.

Adenocarcinoma↗

Early adenocarcinoma of the uterine cervix--its histologic and immunohistologic study.

Eight cases of early adenocarcinoma selected from 101 adenocarcinomas of the uterine cervix were studied to establish the criteria of early adenocarcinoma. Lesions of these 8 cases were small in size. In 7 of 8 cases, these tumors originated in the area of the squamocolumnar junction (SCJ). Tumor cells consisted of two types of atypical columnar cells, i.e., tall columnar cells with enlarged and deeply eosinophilic cytoplasm and clear cells with enlarged and clear vacuoles. Tall columnar cells showed weak or negative reaction to high iron diamine (HID) stain and negative to Alcian blue (AB) stain. Clear cells showed negative reaction to HID stain and positive to AB stain. Although normal endocervical columnar cells showed markedly positive reaction to HID stain and negative reaction to AB stain, invasive adenocarcinoma cells showed similar reaction to early adenocarcinoma cells. From this study, it is surmised that early adenocarcinoma of the uterine cervix originates in the area of the SCJ and consists of tall cells in all cases and clear cells in 4 of 8 cases, and that HID-AB stain is useful in differentiating early adenocarcinoma cells from normal endocervical columnar cells.

Adenocarcinoma↗

[Diagnosis and treatment of cervical dysplasia].

Between 1981 and 1986, 219 patients with cervical dysplasia were treated at the Kyushu University Hospital. All patients were diagnosed by cervical smear, colposcopy, and cervical biopsy and/or endo cervical curettage. They have been followed for more than one year (average 37 months). Of the 219 patients, 63 had mild dysplasia, 99 had moderate dysplasia, and 57 had severe dysplasia. One hundred and forty patients were treated with carbon dioxide laser. The remission rate was 95.0% after one treatment and 98.6% after two treatments. The laser therapy is effective, but a certain rate of recurrence is to be expected. Recently, 23 patients were treated with the cryotherapy and the remission rate was 83%.

Adult↗

[Study on the treatment of malignant vulvar diseases].

During the past 15 years, 8 squamous cell carcinoma in situ and 21 invasive squamous cell carcinoma were treated in our department. Squamous cell carcinoma in situ was adequately treated by either wide local excision or CO2 laser vaporization. Radical vulvectomy was the main treatment modality in our department. Older patients tolerated well the surgery and had better outcome than those treated with radiotherapy alone. Histologically proven groin node metastasis was the risk factor to be overcome.

Adult↗

Elastase digested urokinase (ED-UK).

Elastase digested urokinase (ED-UK) was prepared from human high mol. wt urokinase (HMW-UK). It resembled low mol. wt urokinase (LMW-UK) in its mol. wt, specific activity, and active sites. The steady-state kinetic parameters of each enzyme for the activation of human Glu-plasminogen also resembled each other, as did their amidase parameters (with pyro-Glu-Gly-Arg-pNA).

Chromatography, Affinity↗

Immunochemical determination of the serum protein reacting with antibody against human urinary trypsin inhibitor by single radial immunodiffusion: use of polyethylene glycol.

A single radial immunodiffusion method is described for determining the serum protein which reacts with antibody against the urinary trypsin inhibitor, but does not react with anti-inter-alpha-trypsin inhibitor antibody. Since the amount of this protein could not be determined with an agar plate containing antibody alone, we first prepared an agar plate containing 4% polyethylene glycol 6 000 and 1 mg of anti-urinary trypsin inhibitor gamma-globulin and confirmed that the amount of this protein could be measured accurately from the sizes of precipitin rings after 72 h incubation at room temperature. Levels of this serum protein, alpha 1-antitrypsin, alpha 2-macroglobulin and inter-alpha-trypsin inhibitor were measured in normal human serum by the single radial immunodiffusion method, and it was confirmed that the level of this serum protein did not correlate with the levels of these 3 other proteins.

Antibodies↗