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Biomedical subjects

R Nishimura

Publications and source records attributed to R Nishimura.

At least 217 records · Page 12Linked to original sources
PubMed1991

Follow-up study of camp marathon group psychotherapy for adolescents with emotional disturbances.

Every summer since 1972, the Department of Psychiatry at Fukuoka University has been holding the Camp Marathon Group Psychotherapy (MGP) for adolescents with emotional disturbances. This time we conducted a follow-up survey on 114 camp attendees from 1978 to 1985. Questionnaires were mailed out and we received 56 replies, that is a response rate of 49.1%. The average observation period of the follow-up was 4 years. The results were as follows: Thirty-six cases or 64.3% were making satisfactory progress at the time of the survey. Eight or 14.3% showed no change or showed worsening conditions. Seven or 12.5% cases developed into schizophrenia. Based on these results, we studied roughly what role MGP plays in the therapy of adolescents with emotional disturbances.

Adolescent↗
PubMed1991

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice.

Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor.

Animals↗
PubMed1991

Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes.

Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.

Animals↗
PubMed1991

Reflex activities of the upper airway muscles during experimental nasal occlusion in anesthetized dogs.

Reflex responses of the upper airway muscles during experimental nasal and tracheal occlusions were studied in 21 anesthetized dogs breathing through the nose or a tracheostomy (tracheal cannula). Out of them, five animals were examined for maintained negative and positive pressures applied to the isolated upper airway. When the nose was occluded at end-expiration during three consecutive breathings, the electromyographic (EMG) activity of alae nasi (AN) and posterior cricoarytenoid (PCA) muscle markedly increased. The upper airway was subjected to negative pressure, -2.41 approximately -3.04 kPa (n = 34) by these nasal occlusions. The activity of upper airway muscles was also increased by tracheal occlusions. However, such augmentation of PCA activity was much less in tracheal occlusions than nasal occlusions, whereas there was the smaller difference in AN activity between both occlusions. During nasal occlusions, a prolongation of the inspiratory time (TI) was observed. Furthermore, maintained negative pressure applied to the isolated upper airway provoked an augmentation of PCA activity. Such an augmented EMG activity of PCA and the prolongation of TI were largely diminished by sectioning the superior laryngeal nerves. These results proves that the upper airway muscles play an important role to protect the upper airway from collapsing by nasal occlusions. In addition, it is suggested that a lack of lung volume feedback is substantially concerned with the activation of AN, while negative pressure in the upper airway is essential to stimulate PCA.

Airway Obstruction↗
PubMed1991

[Qualitative analysis of the immunoreactive hCG beta-like substance produced by transitional cell carcinoma of the bladder].

The hCG beta-like immunoreactivity (IR-hCG beta) in the sera and urine of three patients with transitional cell carcinoma of the bladder was characterized by enzyme-immunoassay which specifically recognized the hCG beta-related molecular species (whole hCG, free hCG beta and beta-core fragment). There was a qualitative difference in IR-hCG beta between the serum and the urine in all of the patients. Free hCG beta was exclusively detected in the serum, whereas both free hCG beta and beta-core fragment (beta-CF) could be detected in the urine. Whole hCG could not be virtually observed in the sera and the urine from all the patients examined. The concentrations of urinary beta-CF were consistently much higher than those of urinary and serum free hCG beta in all the patients. The immunohistochemical study was performed by using two kinds of the antibody against the core and the carboxyterminal portions of the hCG beta molecule. Immunoperoxidase staining was positive not only in the syncytiotrophoblastic giant cells but also in the transitional cell carcinoma cells for both antibodies. The present results suggest that free hCG beta is secreted from the tumor cells and metabolized into beta-CF may provide a new index to detect a transitional cell carcinoma of the bladder.

Aged↗
PubMed1991

[Expression of ras oncogene p21 in relation to prognostic factors of human breast cancer].

For the purpose of demonstrating the relationship between the expression of ras oncogene p21 protein and clinico-pathological characteristics which reflected the prognosis, 253 women with breast cancer who underwent mastectomy were analyzed. Ras p21 was detected in 133 (52.6%). In histological types, scirrhous carcinomas were more often ras p21-positive, and papillo-tubular carcinoma were usually negative. And histological grade was significantly correlated with ras p21. The degrees of invasion to fat tissues and infiltration into lymphatic vessels were also significantly correlated with ras p21. Tumors with lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors in smaller tumors, especially in papillo-tubular carcinomas. And patients with elevated ras expression tended to have a poor prognosis. These results suggested that an elevated ras expression may play an important role in the development of aggressive tumors.

Adenocarcinoma↗
PubMed1991

[Molecular heterogeneity of hCG in urine of the patients with trophoblastic diseases].

In addition to whole hCG, hCG beta-related molecular species are also present in the serum and urine of patients with trophoblastic diseases. We simultaneously measured whole hCG, free hCG beta and beta-core fragment in the serum and urine of patients with hydatidiform mole and choriocarcinoma by the highly specific and sensitive sandwich enzyme-immunoassay (EIA) systems using two kinds of antibodies. During the clinical courses of patients, although the whole hCG levels in serum and urine were closely correlated, the concentrations in the serum were almost twice as high as those in the urine. The free hCG beta levels were also closely correlated in serum and urine, but the concentrations of free hCG beta were extremely low as compared with those of whole hCG. Furthermore, free hCG beta/whole hCG ratios were significantly higher in choriocarcinoma patients than in hydatidiform mole patients. While whole hCG and free hCG beta were contained in both serum and urine, the beta-core fragment could be detected only in the urine of the patients. The relative contribution of the beta-core fragment to the total urinary hCG beta-immunoactivity accounted for about 40% in hydatidiform mole and about 70% in choriocarcinoma. We conclude that whole hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggest that the ratios of whole hCG, free hCG beta and beta-core fragment to each other may be useful indices to employ in the differential diagnosis of trophoblastic diseases.

Biomarkers, Tumor↗
PubMed1990

[Electron microscopic and immunological studies concerning the effect on the antitumor activity of sizofiran (SPG) combined with radiotherapy for cervical cancer].

It has been well known that Sizofiran (SPG) cultured from the Schizophyllum commune Fries activates the macrophages and induces the cytotoxic lymphocytes in some cancers. In this study, we observed electronmicroscopically the macrophages around the cancer tissue from the patients with uterine cervical cancer after the treatment with SPG. At the same time, their immune responses were also examined by analyzing lymphocyte subsets, ADCC and NK activity in peripheral blood. A considerable number of erratic macrophage with well developed Golgi apparatus, endoplasmic reticulum and mitochondria were found in the uterine cervical cancer tissue from the patients treated with SPG under radiotherapy. Simultaneously, we identified the lysosome granules with a bright filament structure which appeared to be specific for SPG. In the immune responses evaluated by analyses of peripheral blood, the number of CD 16+ cells and NK activity significantly increased in the patients treated with SPG as compared with non-treated group. The present results indicate that SPG-immunotherapy combined with radiotherapy not only induces the cytotoxic activity of macrophage but also augments NK activity in the patients with uterine cervical cancer.

Carcinoma, Squamous Cell↗
PubMed1990

Altered glycosylation of human chorionic gonadotropin decreases its hormonal activity as determined by cyclic-adenosine 3',5'-monophosphate production in MA-10 cells.

Human chorionic gonadotropin (hCG) purified from pooled urine of normal pregnant women contains four asparagine-linked sugar chains and four mucin-type sugar chains. The structures of asparagine-linked sugar chains of this hormone are constant and site-specific. hCGs obtained from the urine of patients with invasive mole or choriocarcinoma have quite different sets of oligosaccharides although the primary structures of the polypeptides and the numbers of the sugar chains are the same as those of normal hCG. In order to examine the biological activities of these hCGs with altered glycosylation, we measured the amount of cAMP produced in a murine Leydig tumour cell line, MA-10, after incubation with the hCG samples. The extent of sialylation of oligosaccharides in the three hCG samples used in this study were 88% in normal hCG, 82% in invasive mole hCG and 63% in choriocarcinoma hCG. The hormonal activity of invasive mole hCG was slightly lower while that of choriocarcinoma hCG was significantly (P less than 0.01) lower than that of normal hCG. Complete desialylation induced remarkable loss of full activities in all the samples. However, the hormonal activities of the three samples were different even after desialylation. The full activities of the desialylated samples of invasive mole hCG and choriocarcinoma hCG were 78 and 65% of that of desialylated normal hCG. These results indicated that the structures of the neutral oligosaccharide portion are also important for the expression of full hormonal activity.

Animals↗
PubMed1990

Immune mediated skin lesions in a dog with autoimmune hemolytic anemia.

A canine case of Coombs' test positive and antinuclear antibody-negative hemolytic anemia was examined because of the development of skin lesions after 18 months treatment with prednisolone. Histopathological examination of biopsy specimens obtained from skin and oral mucosa revealed the acantholysis, edematous lesions of the stratum basale and mononuclear cell accumulation in the dermis. Deposits of immunoglobulin G and complement factor 3 were detected at the intercellular and dermoepidermal junction by the direct immunofluorescent test. From these results, the case was considered to be an autoimmune disease caused by distinct antibodies against different organs.

Anemia, Hemolytic, Autoimmune↗
PubMed1990

[Development of highly sensitive enzyme immunoassay to measure urinary beta-core fragment in patients with gynecological cancer].

In addition to human chorionic gonadotropin (hCG) and its free subunits, low molecular weight hCG beta-related fragments have been previously demonstrated in pregnancy urine and in the urine of patients with trophoblastic and nontrophoblastic tumors. The urinary beta-core fragment in particular is focused on as a new tumor marker in gynecological malignancies. We developed an EIA for the beta-core fragment using the monoclonal antibody (MoAb229) which specifically recognized the core portion of hCG beta. By measuring with MoAb229-EIA, it was clearly revealed that urine obtained from normal pregnant women as well as from patients with choriocarcinoma and nontrophoblastic ovarian cancer contains a large amount of the beta-core fragment when separated on Sephadex G-100. We conclude that our MoAb229-EIA is a useful tool to use in detecting the beta-core fragment, a new tumor marker, in the urine of gynecological cancer patients.

Antibodies, Monoclonal↗
PubMed1990

[Characterization of immunoreactive hCG beta-subunit in cultured fluids of the cell lines derived from gynecologic malignant tumors].

We characterize the hCG beta-like materials in cultured fluids from 12 different cell lines derived from gynecologic malignant tumors (SKG-1, -2, -3a and -3b cervical squamous carcinoma, SNG-M and -2 endometrial adenocarcinoma, SKN uterine sarcoma, RTSG ovarian undifferentiated adenocarcinoma, RMUG ovarian mucinous adenocarcinoma, RKN ovarian sarcoma, RMG ovarian clear cell carcinoma and NJG gestational choriocarcinoma) by three kinds of enzyme immunoassay (EIA) which were specific for whole hCG, free hCG beta and beta-core fragment, respectively. Of eleven nontrophoblastic cell lines, nine secreted hCG beta-like immunoreactive substance. The above-mentioned three EIAs for each fractionated specimens with gel chromatography on Sephadex G-100 revealed that the immunoreactivity in the SKG-2 and RTSG cultured fluids were totally attributable to free hCG beta but neither to whole hCG nor beta-core fragment. On the other hand, the NJG choriocarcinoma cell line secreted both whole hCG and free hCG beta, no beta-core fragment could be detected in the cultured fluid. The present results suggested that ectopically produced hCG beta-like material may represent the free hCG beta molecule, and that the beta-core fragment may not be a cellular secretory product.

Chorionic Gonadotropin↗
PubMed1990

[Studies on the pathophysiology of paraneoplastic syndromes: both cancer cells and host immune cells are responsible for the pathophysiology of leukocytosis associated with oral cancer].

Leukocytosis associated with malignant disease has been known as a paraneoplastic syndrome and occurs occasionally in patients with oral malignancies. In this study, mechanisms underlying leukocytosis associated with malignancy was investigated, using a squamous cell carcinoma of the maxilla from a patient who manifested marked leukocytosis. When the patient's tumor was inoculated into nude mice, it formed squamous cell carcinoma (MH85) and induced leukocytosis and splenomegaly. Leukocytosis and splenomegaly paralleled tumor growth. Surgical excision of MH85 tumor resulted in a dramatic reduction of leukocyte count and spleen weight, indicating an involvement of humoral mediators released by MH85. MH85 cells conditioned medium (MH85CM) were shown to contain granulocyte-colony stimulating factor (G-CSF) activity, which is a potent growth factor specific for granulocytes. These results suggest G-CSF or G-CSF like substance secreted by MH85 cells is responsible for leukocytosis in MH85 bearing nude mice (MH85 mice) and in the patient. MH85 cell growth was stimulated by G-CSF and inhibited by anti-G-CSF antibody, thus suggesting that G-CSF like substance is a autocrine growth factor for MH85 cells. Splenectomized MH85 mice developed less severe leukocytosis than did non-splenectomized mice. This finding indicated that not only G-CSF like substance secreted by MH85 cells but other humoral factors released by the hyperplastic spleen contribute to the development of leukocytosis. Splenic monocytes derived from MH85 mice and MH85CM-stimulated splenic monocytes showed increased secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), both of which have been reported to induce neutrophilia in animals. Moreover, injection of anti-TNF-antibody into neutrophilic MH85 mice significantly, although not completely, decreased leukocyte count. Thus, it seemed likely that increased secretion of TNF and IL-1 by spleen cells that are stimulated by humoral factors released from MH85 also contributes to the progression of leukocytosis. In splenectomized mice, enlargement of MH85 tumor was retarded and metastases were impaired compared these in nonsplenectomized mice. Coculture of splenocytes from MH85 mice with normal spleen cells, inhibited blastogenesis in response to mitogen. The result suggests that splenocytes from MH85 mice played as immune suppressive cells. MH85CM conferred immune suppressive activity on normal spleen cells. This suppressor cell-inducing factor (SCIF) in MH85CM was found to have an apparent molecular weight of approximately 25kd, and its biological activity was neutralized by anti-G-CSF antibody. Therefore, SCIF secreted by MH85 cells was likely to be G-CSF like substance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

EGF stimulates anchorage-independent growth of a human bladder carcinoma cell line (KU1) with an amplified and over-expressed EGF receptor gene.

Southern blot analysis of 6 human bladder carcinoma cell lines revealed amplification of the epidermal growth factor receptor (EGFR) gene in the KU1 cell line. The amplification of the gene was about 4-fold as compared with that of human placental DNA. Several restriction endonuclease digestions revealed that there was no gross rearrangement of the EGFR gene in KU1. Northern blot analysis showed normal 10 and 5.6 kb of EGFR gene-related mRNA species. 125I-EGF binding revealed 2 distinct EGF binding sites on KU1 cells: high-affinity sites 5.7 X 10(5) receptors per cell with 1.1 nM Kd and low-affinity sites 2.3 X 10(6) receptors per cell with 7.4 nM Kd. The number of the EGFR was compatible with that of the A431 squamous carcinoma cell ine which has an amplified, rearranged and over-expressed EGFR gene. Solid-phase immuno-isolation analysis showed a single 170 kDa EGFR protein in KU1 as well as in A431. Unlike other cell lines with amplified and over-expressed EGFR gene, anchorage-dependent growth of KU1 was stimulated but not inhibited by EGF. Moreover, anchorage-independent growth of KU1 was stimulated by EGF.

Antibodies, Monoclonal↗