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Biomedical subjects

M Miyake

Publications and source records attributed to M Miyake.

At least 19 recordsLinked to original sources

Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung.

BACKGROUND: The level of expression of H/Le(y)/Le(b) antigens is high in various histologic types of lung cancer, a feature that may be related to deletion of A and B blood-group antigens. We evaluated the possibility that expression of this antigen, which can be defined by the monoclonal antibody MIA-15-5, might be of prognostic value, as suggested by our previous observation that MIA-15-5 inhibits tumor-cell motility and metastasis. METHODS: We used MIA-15-5 to stain tissue sections from 149 patients with primary lung cancer whose clinico-pathological histories were well documented. The survival curves for patients whose tumors stained positively were compared with the curves for those whose tumors stained negatively. Multivariate analyses were performed with a Cox proportional-hazards regression model. RESULTS: Among the 149 patients studied, five-year survival in the 91 patients with MIA-positive tumors was significantly lower than survival in the 58 with MIA-negative tumors (20.9 percent vs. 58.6 percent, P less than 0.001). Among the 67 patients with squamous-cell carcinoma, the rates also differed significantly (10.5 percent vs. 62.1 percent, P less than 0.001). The difference in survival between patients with MIA-positive tumors and those with MIA-negative tumors was significant among patients with blood groups A and AB (P less than 0.001), but not among those with blood group B or O (P = 0.071 and 0.068, respectively). Multivariate analysis with the Cox regression model indicated that positivity best correlated with five-year mortality, followed by lymph-node status (N stage) and tumor size status (T stage), whereas sex, age, and blood group did not correlate with mortality. CONCLUSIONS: Positivity for MIA (i.e., immunohistologic staining by MIA-15-5, which defines H/Le(y)/Le(b) antigens) is inversely correlated with survival among patients with primary lung cancer and may be of prognostic value.

ABO Blood-Group System

First establishment of a human monoclonal antibody directed to sulfated glycosphingolipids SM4s-Gal and SM4g, from a patient with lung cancer.

Several human monoclonal antibodies directed to tumor-associated glycolipid antigens have been established, but more than one-half of them react with gangliosides and the others react with neutral glycolipids. We report here the first establishment of a human IgM monoclonal antibody directed to the sulfated glycolipid. This monoclonal antibody, M14-376, did not react with SM3 and SB1a which have a terminal HSO3----3Gal beta 1----R1, but with the simple sulfolipids SM4s-Gal and SM4g which contain a terminal HSO3----3Gal beta 1----O----CH2----R2; however, lyso-SM4s-Gal and lyso-SM4g did not bind M14-376. These results suggest that terminal HSO3----3Gal and part of the hydrophobic region of the glycolipid are recognized by M14-376. Directly biotinylated M14-376 was used for immunohistochemical staining of 140 formalin-fixed, paraffin-embedded lung cancer tissue sections to study the distribution of the antigen. A high incidence of positive staining was found in adenocarcinoma (39.5%, 17 of 43), followed by large cell carcinoma (20.0%, 5 of 25), while this antigen was rarely detected in small cell carcinoma (4.7%, 1 of 21) and squamous cell carcinoma (3.9%, 2 of 51). Thin layer chromatography immunostaining of glycolipids extracted from lung cancer tissues showed the presence of only SM4s-Gal in adenocarcinoma, but SM4g was not found in any subtype of lung cancer. Immunohistochemical staining revealed that this antigen was expressed in normal kidney, testis, and brain, but erythrocytes, granulocytes, and lymphocytes were negative in cytofluorometric analysis.

Adenocarcinoma

Preferential binding of E.coli histone-like protein HU alpha to negatively supercoiled DNA.

Binding specificity of histone-like HU alpha protein to supercoiled DNA was examined by gel retardation assay and chemical probing with OsO4. The latter method was proved to be a unique means for detecting torsional tension restrained in supercoiled plasmid in the presence of HU alpha. It was shown that HU alpha protein has preferential affinity to negatively supercoiled DNA relative to relaxed, nicked and linearized DNAs. There were two modes for binding of HU alpha to the supercoiled DNA: one was the binding associated with topological changes in DNA and the other was relatively strong binding, probably specific to certain particular structures of DNA. It was suggested that HU in vivo interacts preferentially with the regions deformed under torsional stress or with the metabolically active regions along DNA.

Bacterial Proteins

Correlation between killing activity towards the murine L929 cell line and expression of membrane-associated lymphotoxin-related molecule of human lymphokine-activated killer cells.

Human lymphokine-activated killer (LAK) cells expressed a membrane-associated lymphotoxin-related molecule (mLT) which was detected by flow cytometric analysis with anti-lymphotoxin antibody. Upon removal of exogenous interleukin-2 from LAK cell culture medium and another 24 h cultivation, the expression of mLT was decreased. Corresponding to the decrease of mLT expression, the killing activity of LAK cells towards L929 cells was remarkably reduced and killing of MIA PaCa-2 and U937 cells was moderately reduced, whereas killing of Daudi and K562 cells was fully restored. The supernatant of mLT-expressing LAK cells had no cytotoxic activity towards L929 cells in the absence of actinomycin D. Moreover, not only the killing of L929 cells but also that of human tumor cell lines (MIA PaCa-2, U937) by mLT-expressing LAK cells was partially inhibited in the presence of anti-lymphotoxin antibody. These results suggest an involvement of mLT in the killing of some tumor target cells by LAK cells.

Animals

Changes in the productivity of cytokines and active-oxygen in peripheral blood cells following surgery.

An investigation was carried out on the productivity of cytokines and active-oxygen by peripheral blood cells during the pre- and post-operative periods. While the preoperative production of tumor necrosis factor (TNF) and interleukin-1 alpha (IL-1 alpha) was elevated, that of lymphotoxin (LT) and interferon-gamma (IFN-gamma) were slightly suppressed. In the postoperative period the peak TNF and IL-1 alpha and active-oxygen productivity was elevated, while LT and IFN-gamma productivity was suppressed in patients with an intraoperative bleeding volume of more than 1,000 ml compared to those with that of less than 1,000 ml. Thus, stress stimulates the TNF and IL-1 alpha and active-oxygen producing system, that is, the macrophage-neutrophil system, and suppresses the LT and IFN-gamma system, being, the inflammatory helper T cell system, in the early postoperative period.

Adult

High levels of Mn-superoxide dismutase in serum of patients with neuroblastoma and in human neuroblastoma cell lines.

Levels of serum manganese superoxide dismutase (Mn-SOD) in normal children aged from 1 to 14 years and children with various hematological and malignant diseases were determined by enzyme-linked immunosorbent assay (ELISA). In the normal children, the serum Mn-SOD levels gradually increased in proportion to age. By 8 years of age, the Mn-SOD level was nearly at the adult level. The normal values of serum Mn-SOD (mean +/- SD) of children below 4 and above 8 years old were 48 +/- 10.2 ng/ml and 84 +/- 22.5 ng/ml, respectively. Assuming the upper limit of normal Mn-SOD level in serum to be the mean value +/- 2 SD of children at each age, high serum levels of Mn-SOD were found for 8 of 12 patients with neuroblastoma, three of four patients with Wilms tumor, and four of five patients with acute myeloid leukemia. The patients with neuroblastoma exhibited a transient increase in Mn-SOD following chemotherapy, but after 1 week the levels decreased markedly to the control levels. The changes in serum Mn-SOD levels in the patients with neuroblastoma correlated well with the levels of neuron-specific enolase. Mn-SOD was intensely stained in bone marrow cells of patients whose cancer cells had moved into the bone marrow. High levels of Mn-SOD were also found in cultured human neuroblastoma cells. These data indicate that Mn-SOD is expressed in neuroblastoma cells, may serve as one of the diagnostic and prognostic markers for the neuroblastoma, and may be useful to predict the effectiveness of chemotherapy for neuroblastoma and the recurrence of this disease.

Adolescent

An epidemiological study on hyponatremia in psychiatric patients in mental hospitals in Nara Prefecture.

Hyponatremia occurs often in mental illness. The frequency was not noticed because of the uncharacteristic symptoms of mild hyponatremia. Of the 1,114 psychiatric inpatients retrospectively surveyed, 10.5% had hyponatremia. Not only patients with schizophrenia, but also patients with other mental illness, especially with epilepsy, having hyponatremia were confirmed. An early onset, a long duration of psychiatric disorder and a prolonged admission were statistically significant factors. Nicotine abuse was not a significant factor. It was suggested that the pathogenesis of hyponatremia in psychiatric patients might be involved in a chronic course of psychiatric disorders and poor response to psychopharmacotherapy.

Adult

Developmental changes in beta-citryl-L-glutamate concentration and its synthetic and hydrolytic activities in neuronal cells cultured from chick embryo optic lobes.

Developmental changes in the concentration of beta-citryl-L-glutamate(beta-CG) have been examined in the cerebrum and optic lobe of the developing chick brain and in primary cultured neuronal cells from the chick embryo optic lobes with gas chromatographic and HPLC methods originated in our studies. A sharp peak was shown by beta-CG, with a maximal concentration at 13 days of incubation in the optic lobe of the developing chick brain but decreasing markedly to adult levels. The developmental change in primary cultured neurons was similar to that in the optic lobe of the developing chick brain. Changes in synthetic and hydrolytic activities of beta-CG were studied during growth of primary cultured neurons. Incorporation of radioactivities from radiolabeled pyruvate and alanine into beta-CG increased significantly on day 3 of culture, reaching a plateau on day 6, whereas that from radioactive glutamine and glutamate increased gradually from day 3 to day 12 of culture. The hydrolyzing enzyme activity of beta-CG during neuron growth was low until day 3 of culture, when it increased significantly until day 12. Similar developmental changes were observed in the developing chick embryo optic lobes.

Animals

[Dose finding study of sparfloxacin in single-dose therapy for female acute uncomplicated cystitis].

Sparfloxacin (SPFX) is a new quinolone compound with a long half-life of 16 hours and a potent antibacterial activity (MIC90: < or = 0.025 micrograms/ml against Escherichia coli), suggesting that the agent can be effectively used in single-dose therapy for acute uncomplicated cystitis in female patients. To find the optimum dose, the present dose-finding study was conducted. A dose of either 100 mg or 200 mg of SPFX was selected by the double-blind method, and was administered only once (single dose therapy). The clinical efficacy was judged on day 3, 7 and 14 after administration. On day 3, of the 49 pts. in the 100 mg-group, the efficacy rate was 95.9% (excellent rate: 79.6%), and of the 42 pts. in the 200 mg-group, it was 100% (excellent rate: 88.1%). On day 7, of 38 pts. in the 100 mg-group, it was 94.7% (excellent rate: 78.9%), and of 28 pts. in the 200 mg-group, it was 100% (excellent rate: 92.9%). On day 14, of 27 pts. in the 100 mg-group, it was 92.6% (excellent rate: 66.7%), and of 26 in the 200 mg-group, it was 96.2% (excellent rate: 84.6%). Recurrence was observed in 4.8% (1/21) in the 200 mg-group. Therefore, there was no significant difference in the efficacy rate between the two groups, but the rate of excellent responses was higher in the 200 mg-group. Otherwise, the efficacy was estimated to be insufficient in 3 pts. and recurrent in 1 pt. they were examined the findings of detailed urological intractableness. Among 2 pts. in whom the external genitalia and urethra were closely examined, a urethral caruncle was noted in 1 pt. The results of our study indicate that 200 mg of SPFX is recommended as a single dose therapy for acute uncomplicated cystitis in females.

Acute Disease

[Clinical efficacy of levofloxacin (LVFX) single-dose therapy in female acute uncomplicated cystitis].

Treatment of infections by the use of antimicrobial agents should be made essentially in a dose close to the minimally required dose. Acute uncomplicated cystitis in female fits as the subject for a single-dose therapy since it is an infection reactive relatively easily to antimicrobial agents. Accordingly, an assessment has been made regarding the therapeutic results of the single-dose therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200 mg which is a new quinolone. The urinary concentration more than MIC90 to Escherichia coli is sustained for about 3 days by this single-dose therapy. As a result of judging the therapeutic results from the reactions of the three clinical findings of pain on micturition, pyuria and bacteriuria, excellent therapeutic results were obtained with effective rates being 100% (76/76) on the day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three months, as investigated by a questionnaire. As a result of performing close urological examinations such as cystoscopy on six cases with insufficient results or recurrence, we could detect mild underlying conditions which are considered to be intractable factors in the bladder in three cases. From the above results, the single-dose therapy of acute uncomplicated cystitis in the female by LVFX which is a new quinolone was considered to be an excellent therapeutic drug from its characteristics such as its therapeutic results being the same as the conventional therapy by daily administration, excellent drug compliance, low cost, hard selectiveness of resistant strains, less side effects and furthermore it gives the opportunity of detecting a latent and mild underlying condition.

Acute Disease

[Limonoids in Phellodendron amurense (Kihada)].

Limonoids and their glucosides in the seeds and barks of Phellondendron amurense (Kihada) were analyzed. The seeds contained limonin (1950 ppm), obakunone (20 ppm), limonin 17-beta-D-glucopyranoside (820 ppm) and obakunone 17-beta-D-glucopyranoside (1360 ppm). The barks contained limonin (6760 ppm), obakunone (1240 ppm) and nomilin (270 ppm).

Chromatography, High Pressure Liquid

[Stability of body composition in boys and girls 12 through 15 years of age].

Although underwater weighing has been regarded as a representative of the criterion reference methods for determining body composition, this technique is cumbersome for screening. The purpose of the present study was to examine the stability of body composition assessed not only by underwater weighting but also by existing bioelectrical impedance equations and skinfold thickness equations during a 4-week period. Ten male and 10 female junior high school pupils, aged 12 to 15 years, volunteered to serve as subjects. Body density (Db) was estimated by underwater weighing (UW), skinfold thickness (ST) method, and bioelectrical impedance (BI) method. The UW was considered criterion reference method. The underwater weight was the heaviest value that was reproduced twice at least among 5 to 10 measurements. Residual lung volume was estimated "in water," with the subject in the sitting position, by a closed-circuit helium-dilution method. The ST equations used for determination of Db were those developed by Nagamine et al., while in the BI method equations proposed by Nakadomo et al. were applied. The Db for boys by UW did not differ significantly during the 4-week period; however, in girls it was significantly lower in the 2nd test (1.0479 +/- 0.018 g/ml) than in the 1st test (1.0500 +/- 0.019 g/ml). Likewise, the Db estimated by ST and BI methods remained unchanged in boys, while in girls it was significantly lower in the 2nd test (BI: 1.0445 +/- 0.010 vs. 1.0389 +/- 0.013 g/ml). Test-retest reliability of all the three methods for measurements conducted 4 weeks apart were statistically significant (e.g. UW: r = 0.99, ST: r = 0.94, BI: r = 0.89 in girls). In conclusion, the validity of Db estimated by these two methods was found to be insufficient when absolute values are required. However, body composition estimates assessed by ST and BI methods for boys and girls may be stable on a relative basis.

Adolescent

Small cell lung cancer with extensive cutaneous and gastric metastases.

A case of a 60-year-old Japanese woman with small cell lung cancer involving skin and stomach is reported. She was diagnosed as primary small cell lung cancer accompanied by extensive cutaneous metastases. Three months after the last chemotherapy, she complained of nausea and vomiting. Brain CT scan showed no evidence of central nervous system involvement. Upper gastrointestinal study and upper gastrointestinal fiberscopy revealed multiple metastatic gastric tumors. Skin and stomach are uncommon metastatic sites for any malignancy. Furthermore, only a few cases with gastric metastasis could be diagnosed during their lifetime.

Carcinoma, Small Cell

Retroperitoneal ganglioneuroma: a case report and review of the Japanese literature.

A rare case of retroperitoneal ganglioneuroma incidentally found during an annual health examination is presented. The patient was an asymptomatic female, age 26. Physical examination and routine laboratory studies gave normal results. The plasma concentrations and 24-h urinary excretion of catecholamine and its metabolites were within the normal range. The patient was diagnosed as having a left supra-renal mass (6.3 x 3.6 cm) by abdominal ultrasonography, although by image diagnosis the paraadrenal mass could not be discriminated from an adrenal tumor. Operation was performed under the suspicion of a nonfunctioning adrenal tumor. The tumor removed was 8 x 6 x 4 cm, 98 g and was encapsulated. Histopathological diagnosis of retroperitoneal ganglioneuroma was confirmed. Forty-one cases of retroperitoneal ganglioneuroma in the Japanese literature including the present case are reviewed.

Adult

A case of hypersensitivity syndrome resembling Langerhans cell histiocytosis during phenobarbital prophylaxis for convulsion.

The case of a two-year-old girl with generalized histiocytosis, probably induced by phenobarbital, is reported. Symptoms, including intermittent fever, systemic lymphadenopathy, maculopapular skin eruption and hepatosplenomegaly, suggested Langerhans cell histiocytosis. Laboratory examinations revealed leukocytosis with lymphocytosis and eosinophilia and a high LDH serum level, while GOT and GPT were within normal ranges. Cytological studies of lymph node and pleural effusion specimens revealed proliferation and infiltration of Langerhans cell histiocytes with eosinophilia. No histiocyte proliferation was observed in the bone marrow or skin. The clinical manifestations shown by the patient were, however, transient, and improved spontaneously after the discontinuation of phenobarbital. The case was considered to be one of phenobarbital hypersensitivity syndrome based on clinical course and laboratory findings. The mechanism and differential diagnosis of the syndrome are discussed.

Child, Preschool

Transforming growth factor-beta 1 down-regulates expression of membrane-associated lymphotoxin and secretion of soluble lymphotoxin by human lymphokine-activated killer T cells in vitro.

Lymphokine-activated T killer lymphocytes (T-LAK) are important effector cells in various diseases of tissue destructive reactions. They require stimulation with various cytokines to proliferate and mature into function effector cells. We have examined the role of various endogenously and exogenously added cytokines, and tumor necrosis factor (TNF)/lymphotoxin (LT) receptors in this process in vitro. The present report is a continuation of these studies. We found that human T-LAK cells express membrane-associated LT (mLT) but not TNF, and secrete high amount of soluble LT (sLT) but low levels of TNF. When added to the initial cultures or immature T-LAK cells, transforming growth factor-beta 1 (TGF-beta 1) suppressed both mLT expression and sLT secretion by 30-40%. Coculture of mature T-LAK cells with TGF-beta 1 caused 35% down-regulation of both mLT expression and sLT secretion after 18 h of incubation. Kinetic experiments indicated reduction of LT mRNA synthesis could occur in as little as 1 h when cocultured with 5 ng/ml of TGF-beta 1. TGF-beta 1 also reduced mLT induced T-LAK cell cytolytic activity on L929 cells in vitro. It appears TGF-beta 1 can down-regulate LT mRNA syntheses, mLT expression, and sLT secretion of human T-LAK cells in vitro.

Cells, Cultured

Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody M31-15, which inhibits cell motility.

A murine monoclonal antibody (M31-15) was identified using the penetration-inhibiting assay of a human lung adenocarcinoma cell line (MAC10) and remarkably inhibited the phagokinetic tract motility of various cancer cell lines. The antigen, motility-related protein (MRP-1), recognized by M31-15, was 25- and 28-kD proteins, and M31-15 was used to isolate a cDNA clone from a human breast carcinoma cDNA library. Sequence analysis revealed that MRP-1 had strong similarity with a B cell surface antigen (CD37), a melanoma-associated antigen (ME491), the target of an antiproliferative antibody (TAPA-1), a human tumor-associated antigen (CO-029), and the Sm23 antigen of the trematode parasite Schistosoma mansoni.

Adenocarcinoma