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Biomedical subjects

M Kanamori

Publications and source records attributed to M Kanamori.

At least 19 recordsLinked to original sources

Tumor cell attachment to laminin promotes degradation of the extracellular matrix and cell migration in high-metastatic clone cells of RCT sarcoma in vitro.

We investigated the roles of extracellular matrix proteins, laminin and fibronectin, in promoting invasiveness through the extracellular matrix in high-metastatic [RCT(+)] clone cells established from poorly differentiated murine RCT sarcoma in C3H/He mice. Laminin stimulated the type IV collagenolytic activity of RCT(+) cells. After more than 6 h of incubation, the type IV collagenolysis of the cell-conditioned medium was significantly higher in laminin-treated groups compared with the control. The migration activity of RCT(+) cells was stimulated by laminin. However, fibronectin did not influence the type IV collagenolysis or cell migration in this clone cell. The amino acid sequence YIGSR, which is derived from laminin, inhibited the laminin-mediated cell attachment and the laminin-promoted type IV collagenolysis, as well as cell migration of RCT(+) cells. RGD derived from fibronectin did not influence the cell attachment to laminin or Matrigel in this clone. In the invasion assay employing a Matrigel coated filter in a Boyden chamber, YIGSR showed greater inhibition of invasion through the Matrigel than did RGD with RCT(+) cells. YIGSR might inhibit the promoted-matrix degradation and cell migration in response to the cell attachment to laminin by competing with laminin for binding to cell surface laminin receptor. We suggest that laminin-mediated cell attachment to the extracellular matrix may play a role in promoting the matrix degradation and cell migration during metastatic cascades.

Amino Acid Sequence

Solitary T-cell lymphoma of the sciatic nerve: case report.

In lymphoproliferative disorders, primary involvement of the peripheral nerve is rare. This report describes a very rare case of a solitary extranodal T-cell lymphoma of the sciatic nerve. Magnetic resonance imaging and gallium scintigraphy were useful for the identification of the lesion of the sciatic nerve. The histological analysis of an open-biopsy specimen disclosed a T-cell lymphoma (non-Hodgkin's lymphoma, lymphoblastic type). Radiotherapy and chemotherapy resulted in a partial regression of the disease.

Adult

An indicator quantitatively comparing two treatment effect sizes on responder and non-responder groups--exponential of estimated interaction parameter.

Sometimes a specific treatment is effective in one subgroup but not in another. An indicator allowing quantitative comparison of treatment effect in two subgroups would be useful in clinical medicine. We have developed such an indicator. It is obtained by calculations using Cox's proportional hazard or logistic model with therapy, subgroup, and confounding explanatory variables. The parameter of the interaction between therapy and subgroup can be estimated and tested statistically. The exponential value of the interaction parameter is what we tentatively call the "hazard ratio ratio", meaning the ratio between the treatment effects in two subgroups. The 95% confidence interval of the indicator can also be calculated. As a numerical example, the hazard ratio between the survival times of postoperative gastric cancer patients treated by adjuvant immunochemotherapy and patients without adjuvant immunochemotherapy in a subgroup with high serum glycosidically bound sialic acid (SA) level was lower than that in a low-SA subgroup using an estimate for hazard ratio ratio of less than 0.5 with statistical significance. We propose this indicator be used as a "responder/non-responder ratio" of therapy effect.

Antibiotics, Antineoplastic

Calcitonin receptors on neoplastic mononuclear cells cultured from a human giant-cell tumor of the sacrum.

Saturable, specific, high-affinity calcitonin receptors were demonstrated in cultured neoplastic mononuclear spindle cells from a giant-cell tumor of the sacrum of a 38-year-old woman. The receptor was analyzed by autoradiography and 125I-calcitonin binding assay. Binding reversibility of 125I-calcitonin to the cells was not complete and the structural specificity was indicated by the inability of unrelated hormones to compete with calcitonin. The 24,000 receptors/cell and dissociation constant (Kd) of 8.0 x 10(-10) M, calculated from linear Scatchard plots, suggested the existence of a single class of calcitonin binding sites in the neoplastic mononuclear cells. Flow-cytometric analysis in the primary culture showed that mononuclear cells consisted of mononuclear round cells of monocyte/macrophage lineage, which express more calcitonin receptors than neoplastic mononuclear spindle cells. Administration of calcitonin caused morphological and physiological alterations, resulting in involutional or irregular cytoplasmic shapes and inhibition of DNA synthesis in neoplastic mononuclear cells accompanied by the escape phenomenon. Cells preincubated with calcitonin showed a decrease in 125I-calcitonin binding activity, which could account for the escape phenomenon. The decrease in 125I-calcitonin binding was rapid, but the recovery was not observed for 24 h after elimination of calcitonin. This decrease may be caused by the disappearance of residual receptors or by a decrease in calcitonin affinity. The calcitonin-induced morphological changes and the inhibition of DNA synthesis of cells were revealed to be mediated by calcitonin receptors.

Adult

Effects of epidermal growth factor on invasiveness through the extracellular matrix in high- and low-metastatic clones of RCT sarcoma in vitro.

We investigated the invasiveness of tumor cells through the extracellular matrix and the influence of epidermal growth factor (EGF) on tumor cell invasion using in vitro systems in high-[RCT(+)] and low-metastatic [RCT(-)] clones established from poorly differentiated murine RCT sarcoma in C3H/He mice. In the invasion assay using a filter coated with reconstituted basement membrane (Matrigel) in a Boyden chamber, RCT(+) cells were more invasive than RCT(-) cells. The attachment of RCT(+) cells to extracellular matrix components and the degradation of type IV collagen by the cells were significantly greater than with RCT(-) cells. However, there was no significant difference in the migration of cells to the extracellular matrix components between cultured RCT(+) and RCT(-) cells. These findings suggested that the different invasiveness of these clone cells was associated with the difference in the ability of attachment to and degradation of the matrix. The level of laminin receptor expression in RCT(+) cells was about four-fold that in RCT(-) cells and laminin stimulated the type IV collagenolytic activity of RCT(+) cells, suggesting that RCT(+) cell attachment to laminin via laminin receptor on the cell surface induced the production of type IV collagenase by the tumor cells. EGF did not affect the invasiveness of RCT(-) cells. In RCT(+) cells, EGF stimulated the invasiveness through Matrigel, the attachment to extracellular matrix components and the degradation of type IV collagen through high-affinity EGF receptors (EGFR), with Kd of pM order, while the migration to the matrix was not influenced by EGF. These findings suggest that the stimulatory effect of EGF on invasion is related to the acceleration of cell adhesion, and the degradative cascade of the extracellular matrix and high-affinity EGFRs play an important role in the effect of EGF on in vitro invasiveness in this tumor.

Animals

Serum levels of laminin, type IV collagen and type III procollagen peptide as markers for detection of metastasis.

We investigated the clinical usefulness of serum laminin, type IV collagen and type III procollagen peptide (PIIIP) as markers for detection of metastasis in patients with primary or metastatic bone and soft part tumors. The subjects consisted of 28 patients with metastatic bone tumors, 18 with primary bone tumors (benign; 10, malignant; 8), 22 with primary soft part tumors (benign; 12, malignant; 10), 18 with cancer without metastasis (as controls to metastatic bone tumor) and 60 healthy controls. Elevated levels of serum laminin, type IV collagen and PIIIP were not associated with any specific histological subtype, tumor size or location, and were clearly related to evidence of metastasis. Mean serum concentrations of laminin, type IV collagen and PIIIP were significantly higher in patients with metastasis than in patients without metastasis. Positive correlations were observed among serum laminin, type IV collagen and PIIIP levels in tumor patients. The sensitivity values for laminin, type IV collagen and PIIIP in detecting metastasis were 83.7%, 83.3% and 80.5%, respectively, with specificity of 90.0%, 86.1% and 86.1%. When two of the three markers were evaluated in identical blood samples, combined sensitivity and specificity values exhibited further increases as compared to the sensitivity and specificity of each marker. The use of all three markers led to the best combined sensitivity and specificity. These findings suggest that the combination of these markers would be a valuable screening test in predicting metastasis.

Analysis of Variance

beta-Lactam resistance of motile Aeromonas isolates from clinical and environmental sources.

The MICs of various beta-lactams for 182 isolates of Aeromonas species, i.e., A. hydrophila (n = 101), A. sobria (n = 69), and A. caviae (n = 12), from clinical and environmental sources were determined by an agar dilution technique. All strains were resistant to ampicillin and susceptible to aztreonam. A. sobria and A. caviae demonstrated lower resistance rates than A. hydrophila. Penicillin-hydrolyzing beta-lactamases were detected in all strains.

Aeromonas

Phosphorus-31 nuclear magnetic resonance study of energy metabolism in intact slow- and fast-twitch muscles of rats.

The time course of the catabolism of phosphorylated metabolites was studied by phosphorus-31 NMR(31P NMR) spectroscopy over a 6-h period after the isolation of rat slow- and fast-twitch muscles, the soleus and the extensor digitorum longus (EDL), respectively, obtained without any muscle damage. In both muscles, rapid depletion of creatine phosphate was followed by a decrease in ATP. These high-energy phosphates disappeared earlier in the soleus than in the EDL. In both muscles, inorganic phosphate (Pi) largely increased in a biphasic pattern, and sugar phosphates (SP) also showed considerable increase. The NMR-visible total phosphates (NTP) increased significantly in the soleus during the latter stage of observation. This increase in NTP was attributed to an increase in Pi. Although the two muscles showed the same initial (7.21) and final (approximately 5.9) intracellular pH (pHi), the pattern of pHi decline differed between these muscles. The rapid fall of pHi in the soleus in the early stage suggests that nonlactic acid acidosis plays a significant role in postmortem changes.

Animals

Inhibitory specificity against various trypsins and stability of ovomucoid from Japanese quail egg white.

The inhibitory specificity and stability of ovomucoid from Japanese quail egg white (OMJPQ) were examined to understand its nutritional significance. OMJPQ showed strong inhibitory activities toward trypsins from various origins including human, and the trypsin inhibitions occurred at molar ratios of enzyme to inhibitor between 1/1 and 2/1. On the other hand, an equimolar mixture of the second and third domains of OMJPQ inhibited bovine trypsin more strongly than the corresponding native OMJPQ did. This distinction was partly explained by the presence of steric hindrance on the formation of a 2:1 trypsin-OMJPQ complex. OMJPQ retained about 100% of its original activity over a pH range from 1 to 12 after a 24-h incubation at 37 degrees C. The inhibitor was most thermostable between pH 2 and 5, where more than 70% of its original activity was maintained after a 1-h incubation at 100 degrees C and about 25% of the activity even after a 30-min incubation at 121 degrees C. OMJPQ was also considerably resistant to pepsin attack. Pepsin digestion of the protein resulted in only about 40% loss of the original trypsin-inhibitory activity even after a 24-h digestion. Furthermore, the addition of bovine serum albumin to the digestion mixture brought about rapid elevation in the trypsin-inhibitory activity during an initial 30-min digestion. SDS-PAGE and immunoblot suggested that this was due to the liberation of active inhibitory domains from the native molecule by inter-domain proteolysis.

Animals

Publication probability of a study on odds ratio value circumstantial evidence for publication bias in medical study areas.

A summarized odds ratio, calculated from odds ratios of published studies in a meta-analysis, may be overestimated because of publication bias. A method has been developed estimating indirectly the summarized odds ratio of all studies in a given research area, including not only those published but also unpublished. In the present study, a publication probability according to odds ratio value was obtained from the probability density function of all the studies, and a histogram of those published. A publication probability, according to odds ratio value, enables us to infer the quantitative relationship between publication probability and odds ratio. A notable nonpublication of studies whose odds ratios were close to unity was shown from examples of studies on the relationship between passive smoking and lung cancer, whereas nonpublication of studies whose summarized odds ratio was located far from unity was not detected from examples of studies on the relationship between cryptorchidism and testicular cancer. In both study areas, however, the differences between the summarized odds ratios, either with or without the hypothetical unpublished studies, were not large. The small difference, however, should not be ignored, when the study area is recognized as a social problem.

Cryptorchidism

Effects of moderate hypercapnia on hypothermia induced by cold He-O2 in rats.

1. Effects of moderate hypercapnia (10% CO2) on rectal temperature, oxygen consumption and body weight loss were examined during and after acute hypothermia induced by cold and helium-oxygen. 2. Hypothermia induction time was reduced significantly by hypercapnia. Rewarming tended to be faster in hypercapnic animals than in normocapnic animals. 3. Hypercapnia significantly reduced body weight loss when measured during hypothermia and during normothermia after rewarming. 4. Oxygen consumption during cooling was decreased by hypercapnia. 5. Exposure to 10% CO2 during cooling may spare energy substrate and favor survival in hypothermia.

Animals

Association between chromosome 11q13 amplification and prognosis of patients with oesophageal carcinomas.

Ninety pairs of normal and tumour tissue DNAs were isolated from paraffin-embedded blocks of advanced oesophageal carcinoma cases and examined for gene amplification at chromosome 11q13 by dot-blot hybridisation using the int-2 gene as a probe. 22 of 90 carcinomas (24%) showed more than two times amplification. Although no significant correlation was observed between gene amplification and histological type or metastasis to lymph node, a tendency for deeper invasion to be associated with more frequent amplification was observed. In relation to prognosis, patients with amplification had a lower survival rate than those without amplification. This tendency was evident both in the group with well differentiated type carcinoma and in the group which had no metastasis to lymph node. Thus, gene amplification of the int-2 locus may be a useful prognostic factor.

Chromosomes, Human, Pair 11

[O serogroup and virulence factors of motile Aeromonas].

A total of 182 isolates of motile Aeromonas from patients with diarrhea and environmental sources was investigated for hemolytic activity to rabbit erythrocyte and cytotoxicity to HeLa 229 cell. Furthermore, the relation between O serogroup and virulence factors, which were lethal to mouse and autoagglutination, were investigated. There were many strains possessing both the hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, suggesting that these activities were associated with intestinal pathogenecity. Although there was a clear correlation between hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, the correlation was not found in A. hydrophila from domestic cases of diarrhea and A. sobria from overseas traveller's diarrhea. Especially, some A. hydrophila isolates from domestic case of diarrhea produced only hemolysin. These results indicated that there was a difference in specificity between the toxins accounted for hemolytic and cytotoxic activities, and more than two different toxins were developed. O serogroups 11, 34, 14, 16, and 35 in that order were the most frequent serogroups. About half of O11 and O34 strains possessed lethal activity to mouse. Autoagglutination phenomenon did not seem to be associated with the lethal activity. In O11 strains, high cytotoxic titer was more frequently found in lethal activity positive-strains than in the activity negative-strains, suggesting that cytotoxicity contributed preferentially to lethal activity to mouse. But such a correlation was not found in O34 strains, so other virulence factors than hemolysin and cytotoxin may be associated with the lethal activity.

Aeromonas

Estimating a summarized odds ratio whilst eliminating publication bias in meta-analysis.

Publication bias is a recognized phenomenon, i.e. studies with statistically significant results are more likely to be published than those finding no difference between the groups studied. Summarized odds ratio calculated from odds ratios of published studies in a meta-analysis may be overestimated because of publication bias. This is a significant problem in research areas involving weak associations between causes and results. The magnitude of publication bias in a given research area cannot be determined directly. The present study enables us to calculate the summarized odds ratio of hypothetical unpublished studies from odds ratios of published studies indirectly, employing a moment method by assuming the natural logarithm value of the odds ratio to be distributed normally. We can then estimate summarized odds ratio in all studies, which include not only those published but also those unpublished. When these studies are homogeneous in quality and their odds ratios homogeneous in quantity, the method can eliminate publication bias.

Bias

Radioimmunoassays for melatonin using an antiserum raised against a novel antigen.

The highly specific antiserum to melatonin (MT) was produced, and the sensitivity and specificity of the radioimmunoassays (RIAs) using this antiserum was investigated. An immunogen was synthesized by binding 6-hydroxy-melatonin (6-OH-MT) to bovine serum albumin with a spacer of 6-bromohexanoic acid ethyl ester. Rabbits were immunized subcutaneously once a month with 1.0 mg of the immunogen for 7 months. The antiserum was characterized by a crossreactivity test by RIA using 125I-labelled MT. The antiserum specifically recognized MT but hardly did other analogues except for 6-OH-MT with a crossreactivity of only 0.4%. Two RIAs were established using [o-methyl-3H]MT and 2-[125I]iodo MT. In both RIAs, inhibition curves for MT were obtained in the range of 10 pg to 10 ng and 1-2 ng of MT inhibited the value of the assay at "0" by half. The similarity of the RIAs in sensitivity and inhibition by unlabelled MT is discussed on the basis of the structures of radioactive MTs and that of the immunogen.

Animals

A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

Animals