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Biomedical subjects

N Toki

Publications and source records attributed to N Toki.

At least 19 recordsLinked to original sources

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

Plasminogen activator activity levels in patients with Behçet's syndrome.

We studied the plasminogen activator levels in plasma samples of 37 patients with Behcet's syndrome. A significant decrease of plasminogen activator activity level was shown by the euglobulin lysis time method, the amidolytic activity level (Testzym method), and the fibrin plate method. Such a decrease may be associated with the severity of Behcet's syndrome.

Behcet Syndrome

A case of ruptured hepatoma followed by elastase-induced disseminated intravascular coagulation.

In the present study, the first case of ruptured hepatoma followed by disseminated intravascular coagulation is reported. An elastase-like enzyme which possessed elastolytic and caseinolytic activities was confirmed from patient plasma. On the other hand, no elastase activity was detected in the plasma of patients with hepatitis, liver cirrhosis or hepatoma without disseminated intravascular coagulation. The patient plasma did not possess H-D-Val-Leu-Lys-p-nitroanilide hydrochloride, succinyl-L-alanyl-L-alanyl-p-nitroanilide, and pyro-Glu-Pro-Val-p-nitroanilide amidolytic activities. However, when chromatographed on Sephadex G-200, the presence of low-molecular weight plasminogen was confirmed. Its molecular weight was approximately 52,000. A slight decrease of alpha 2-plasmin inhibitor was noted, but no decrease of alpha 2-macroglobulin was detected.

Aged

Transport of urokinase across the intestinal tract of normal human subjects with stimulation of synthesis and/or release of urokinase-type proteins.

Oral administration of clinical-type high molecular weight urokinase (HMW-UK) in a single dose of 30,000-60,000 International Units (IU) in enteric-coated capsules, in a group of normal human subjects, induced a plasma fibrinolytic state suggesting transport of HMW-UK across the intestinal tract. Other groups of human subjects were given a single dose of 120,000 IU daily of pure HMW-UK for 1 d and 7 d together with a placebo dose, all of the ingredients except urokinase (UK), daily for 7 d. UK-type proteins were isolated from the plasma of blood samples drawn 6 h after administration of the final dose, by a sequential two-step affinity chromatography method first with [N alpha-(epsilon-aminocaproyl)-DL-homoarginine hexylester]-Sepharose and second with a specific rabbit anti-HMW-UK-IgG-Sepharose. The yield of UK-type proteins from the 7-d group, 0.79 mg/dl, was approximately twofold greater than that obtained from either the placebo or 1-d groups. The specific plasminogen activator activity of the 1-d and 7-d groups were similar, 508 and 537 IU/mg protein, respectively; negligible plasminogen activator activity could be detected in the placebo group. The kinetics of activation parameters of human Glu-plasminogen of the UK-type protein, isolated from the 1-d group, were similar to those obtained with urinary HMW-UK. The UK-type proteins isolated only from the 7-d group showed, in sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, a major protein band of molecular weight 53,000 in the same position as HMW-UK. In addition, two other major protein bands of approximately 140,000 and approximately 120,000 mol wt were found in the 7-d placebo-, and 1-d groups, and also in the 7-d group. The 53,000 mol wt protein, about 50% of the total protein in the 7-d group, was further purified by preparative SDS-polyacrylamide gel electrophoresis, and found to be a two-chain protein with a specific activity of 1,241 IU/mg protein. The protein showed common antigenic determinants with urinary HMW-UK. The oral administration of 120,000 IU HMW-UK to human subjects for 7 d stimulated the synthesis of a UK-type protein of 53,000 mol wt, probably the zymogen, from either the liver or vascular endothelium, which was released into the circulation, and converted into active UK by circulating plasmin. The induction of the fibrinolytic state produced the conversion of native circulating Glu-plasminogen into the degraded Lys-plasminogen form, which was found in large amounts in the plasma of the 7-d group. The new plasma components, e.g., the 53,000-mol wt UK-zymogen and Lys-plasminogen, could play an important role in clot resolution of the fibrin-thrombus in thromboembolic diseases. Oral administration of HMW-UK has been shown to be clinically effective in patients with cerebral thrombosis in a multicenter double blind study.

Adolescent

Cysteine protease inhibitors isolated from human malignant melanoma tissue.

Cysteine protease inhibitors that specifically reacted with several cysteine proteases were found in KSCN extract of human melanoma tissue. From 30 gm of the tissue, approximately 593.5 U inhibitor was obtained. The inhibitors were adsorbed on a papain-Sepharose column and could be eluted with 10 mmol/L phosphate buffer, pH 6.0, containing NaCl or KCl, or with 20 mmol/L acetate buffer, pH 4.0, containing KSCN. They revealed a strong inhibitory activity for cysteine proteases such as ficin, papain, and cathepsin B, but did not react with cysteine protease bromelain or serine protease trypsin. No immunologic relationship was confirmed between the inhibitor and other well-known plasma inhibitors such as alpha 1-antitrypsin, alpha 2-macroglobulin, alpha 1-antichymotrypsin, antithrombin III, C1-in-activator, and alpha 2-plasmin inhibitor. With Sephadex G-100, two main peaks of molecular weight 40,000 and 10,000 were detected in the KSCN extract of the human melanoma tissue. However, the inhibitors revealed three molecular weights of 10,000, 25,000, and 80,000 when estimated by Sephadex G-100 gel filtration after papain-Sepharose affinity chromatography. On the other hand, the molecular weights of the inhibitors changed to two peaks of 25,000 and 10,000 on rechromatography with a papain-Sepharose column.

Adsorption

The transport of 125I-labeled human high molecular weight urokinase across the intestinal tract in a dog model with stimulation of synthesis and/or release of plasminogen activators.

In an attempt to elucidate the mechanism of fibrinolytic enhancement by orally administered urokinase, studies on the intestinal transport of urokinase were carried out, using 125I-labeled human high mol wt urokinase, administered intraduodenally in the experimental dog model with a saphenous vein thrombus. Using the plasma sample obtained from blood 45 minutes after intraduodenal administration of the urokinase, protein fractions were isolated by a sequential two-step affinity chromatography method, first with [N alpha-(epsilon-aminocaproyl)-DL-homoarginine hexylester]-Sepharose followed by a specific anti-human low mol wt urokinase rabbit IgG-Sepharose (adsorbed-eluted and unadsorbed). Each of the isolated protein fractions was further purified by gel filtration on Sephacryl S-300. The proteins isolated by the two-step affinity chromatography method were transported human urokinase with radioactivity in the adsorbed-eluted fraction, and newly synthesized and/or released dog plasminogen activators, probably urokinase-type and tissue-activator type, without radioactivity. In an antibody quenching assay, dog urokinase and the immuno-affinity unadsorbed fraction were not neutralized, but the immuno-affinity adsorbed-eluted fraction was completely neutralized by the specific anti-urokinase IgG antibody. Proteins isolated from control plasma (after administration of saline) by the two-step affinity chromatography method in the unadsorbed fraction had negligible amounts of activator activity. In these studies, we were able to show that synthesis of plasminogen activators was stimulated, with the activators being released, from either the liver or the vascular endothelium. Also we showed that urokinase is transported across the intestinal tract in the dog model.

Animals