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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 703 records · Page 39Linked to original sources

Inhibitory effects of adhesion oligopeptides on the invasion of squamous carcinoma cells with special reference to implication of alpha v integrins.

We studied invasion-related adhesion events in vitro using three squamous carcinoma cell lines (HSC-3), poorly differentiated type; OSC-19, well-differentiated type; and KB cells, undifferentiated type). An in vitro invasion assay through matrigel in the transwell chamber revealed that HSC-3 cells were most invasive, OSC-19 cells moderately invasive and KB cells least invasive. Inhibition assay of invasion using synthetic peptides RGD, RGDV, RGDS, RGDT, IKVAV and YIGSR, showed that invasion of the three cell lines was significantly inhibited by RGDV. There were other peptides that inhibited invasion significantly including IKVAV for HSC-3, and RGDS and YIGSR for OSC-19. HSC-3 cells and OSC-19 cells adhered to fibronectin, laminin, vitronectin, and type IV collagen, and KB cells did not adhere to laminin but did to fibronectin, vitronectin and collagen type IV. Pretreatment of cells with RGDV peptide in the attachment assay reduced the ability of these cells to bind to vitronectin and fibronectin more efficiently than pretreatment with RGDS. Anti-alpha v antibodies inhibited adhesion of HSC-3, OSC-19 and KB cells to vitronectin, but anti-beta 1 antibodies did not inhibit adhesion. Immunofluorescent microscopic examinations showed that all cell lines were positive for anti-beta 5 and anti-alpha v antibodies, and only HSC-3 cells were positive for anti-beta 3 antibody. alpha 5 beta 1 was not clearly demonstrated in any of the cell lines. RGDV was the most effective inhibitor of squamous cell carcinoma invasion among the synthetic oligopeptides used in this experiment, and it is suggested that it affects alpha v beta 3- and/or alpha v beta 5-mediated carcinoma cell invasion.

Amino Acid Sequence↗

Assessment of adrenal surgery on creatinine clearance in patients with phaeochromocytoma.

Sequential changes in creatinine clearance (Ccr) were determined in 14 patients undergoing operation for phaeochromocytoma. All patients had been given alpha-adrenergic antagonists 2 weeks before surgery. In the younger group (mean age 40 +/- 2 years), Ccr improved following adrenal surgery. Urinary concentrations of epinephrine, norepinephrine and total catecholamines correlated inversely with Ccr. A similar inverse relationship was noted between tissue norepinephrine concentration expressed as microgram/g and Ccr to a lesser extent. In older patients (mean age 69 +/- 2 years) Ccr remained unchanged by this surgical procedure. No significant correlations were found between both parameters in the older group. It appears reasonable to presume that excessive amount of catecholamine plays an important role in the impairment of Ccr in relatively young patients with phaeochromocytoma, but other possibilities as regards the sequence of this phenomenon must be pursued in older patients.

Adrenal Gland Neoplasms↗

Estimation of the total saliva volume produced per day in five-year-old children.

Fifteen boys and 15 girls were asked to record for 2 days the time spent awake, eating meals or snacks, and sleeping. The salivary flow rates elicited by chewing foods were also determined. The mean flow rate (+/- SD) of unstimulated saliva was 0.26 +/- 0.16 ml/min and that of saliva while chewing six different foods was 3.6 +/- 0.8 ml/min. The mean times spent eating, and awake but not eating, were 80.8 +/- 27.3 and 820 +/- 59 min, respectively, and the volumes of saliva produced during those periods would average about 288 and 208 ml, respectively. If the flow rate is virtually zero during sleep, the estimated total salivary volume produced per day is calculated to be about 500 ml.

Child, Preschool↗

Enhancement of phagocytosis in mouse macrophages by pituitary adenylate cyclase activating polypeptide (PACAP) and related peptides.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) and related peptides on phagocytosis of fluorescent latex beads by mouse peritoneal macrophages were examined using flow cytometry (FCM). PACAP38, PACAP27 and vasoactive intestinal peptide (VIP) enhanced phagocytosis in a dose-dependent manner. Relative potencies of related peptides at a concentration of 10(-6) M were PACAP38 > PACAP27 > VIP > secretin > glucagon > (peptide with NH2-terminal histidine and COOH-terminal methionine amide, in short PHM). PACAP(6-38) was as effective as PACAP38. PACAP(6-27) enhanced phagocytosis more effectively than did PACAP27. PACAP(28-38) slightly enhanced phagocytosis. The present result suggest that PACAP38 is one of the mediators that the nervous system uses to modulate the immune system.

Animals↗

Brain stem cheiro-oral syndrome: neurological signs for brain stem lesions.

Cheiro-oral syndrome (COS) is characterized by a sensory disturbance in one hand and the ipsilateral oral corner. It is usually due to a lesion in the parietal cortex, thalamocortical projections or thalamus. Brain stem lesions may rarely produce COS. We present two COS patients with midbrain infarction and pontine hemorrhage, respectively. In our patients, unilateral oculomotor nerve palsy or medial longitudinal fasciculus syndrome concurred with sensory disturbances of cheiro-oral distribution. COS produced by cortical/thalamic lesion is not accompanied with such oculomotor signs. Thus, oculomotor deficits are decisive in differentiating brain stem from cortical or thalamic COS.

Aged↗

Asymmetry in plantar grasp response during infancy.

The neurologic outcomes of 61 children with asymmetric plantar grasp responses during infancy were evaluated during a follow-up period of 2.8-11.9 years (mean: 6.1 years). They all had perinatal risk factors and/or neurologic signs except for asymmetric plantar grasp responses recorded during infancy. The outcomes consisted of cerebral palsy in 38, delay in motor development in 6, mental retardation in 3, borderline intelligence in 9, and normal in 5. Most patients demonstrated concordance between the side of the abnormal response and the laterally in motor function and abnormal computed tomographic findings. The asymmetry in the plantar grasp response strongly suggests the existence of brain dysfunction. Infants with this asymmetry should be carefully monitored for the development of neurologic abnormalities.

Brain↗

Interaction between undulated and Patch leads to an extreme form of spina bifida in double-mutant mice.

The aetiology of spina bifida involves genetic and environmental factors, which may be why major genes contributing to pathogenesis have not been identified. Here we report that undulated-Patch double-mutant mice have a phenotype reminiscent of an extreme form of spina bifida occulta in humans. This unexpected phenotype in double-mutant but not single-mutant mice shows that novel congenital anomalies such as spina bifida can result from interaction between products of independently segregating loci. This example of digenic inheritance may explain the often sporadic nature of spina bifida in humans.

Abnormalities, Multiple↗

Association of cigarette smoking and CYP1A1 polymorphisms with adenocarcinoma of the lung by grades of differentiation.

We have previously reported on an association of genetic susceptibility to squamous cell carcinoma of the lung with two polymorphisms of the CYP1A1 gene, an MspI polymorphism and an isoleucine-valine (Ile-Val) polymorphism. We report here that the two CYP1A1 polymorphisms were associated with current or ex-smokers with adenocarcinoma of the lung. We first compared smoking status of the patients by differentiation grades of adenocarcinoma. Proportion of current or ex-smokers and their cigarette consumption was the highest among the poorly differentiated. Second, the two polymorphisms of CYP1A1 were examined among current or ex-smokers with three differentiation grades, and we found that poorly differentiated adenocarcinoma showed significantly high frequencies of genotypes C and Val/Val, which have been found to be 'susceptible' in squamous cell carcinoma of the lung. Third, a case-control study was carried out to estimate the genetic risk for CYP1A1 genotypes to differentiation grades, selecting only current or ex-smokers in patients and controls. Current or ex-smokers with 'susceptible' genotype C or Val/Val were at significant risk, with an odds ratio of 3.25 or 3.22 (95% confidence interval (CI), 1.40-7.56 or 1.00-10.32) for adenocarcinoma as a whole, respectively. The odds ratio increased to 4.51 or 4.09 (95% CI, 1.73-11.78 or 1.12-14.91) for poorly differentiated, while the odds ratios for other differentiated grades were not significant. Finally, a relation of the genetic risk to cigarette dose levels was evaluated.

Adenocarcinoma↗

A mouse monoclonal antibody, S2n8, detects a 140 kDa protein on the surface of human endometrial stromal cells and decidual cells.

We developed a mouse monoclonal antibody, S2n8, by immunizing mice i.p. with human decidual cells collected in the first trimester of pregnancy. By indirect immunofluorescence staining of frozen sections, S2n8 was found to react with decidual cells and endometrial stromal cells throughout the menstrual cycle, but not with endometrial glandular cells or with the endometrial surface epithelium. Judging from the fluorescence intensity, the antigen expression on stromal cells was weak in the proliferative phase, and became stronger in the secretory phase. Decidual cells in the first trimester of pregnancy and decidual cells at term showed strong expression of this antigen. Indirect immunofluorescence staining of enzymatically dispersed decidual tissue revealed that the S2n8 antigen was expressed on the decidual cell surface. Flow cytometric analysis of 12 freshly prepared stromal cell-enriched cell suspensions showed that 74.8-94.2% (mean +/- SD 86.1 +/- 6.6%) of the cells carried the antigen. The expression of S2n8 antigen on cultured stromal cells was enhanced by the addition of oestradiol and/or progesterone. The antigenic molecule was purified by immunoaffinity chromatography from decidua collected in the first trimester of pregnancy, and the molecular weight was estimated to be approximately 140 kDa. These findings indicate that the S2n8 antigen is a useful cell surface marker for stromal cells/decidual cells and is associated with their differentiation.

Animals↗

Kinetic analysis of endocytosis and intracellular fate of liposomes in single macrophages.

Endocytosis and the intracellular fate of liposomes in single mouse peritoneal macrophages were examined kinetically by fluorescence microphotometry. Liposomes labeled with N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine or containing 8-amino-naphthalene-1,3,6-trisulfonate were promptly incorporated into macrophages on incubation at 37 degrees C, but fluorescence increase caused by hydrolysis of 4-methylumbelliferyl-beta-D-glucoside encapsulated in the liposomes was observed after 30 min of incubation. The fluorescences of calcein and 8-hydroxy-1,3,6-pyrenetrisulfonate (HPTS) in liposomes, which were respectively quenched statically due to high concentration and dynamically by a co-entrapped fluorescence quencher, p-xylene-bis-pyridinium bromide, also increased from 30 min after the start of liposome incorporation, indicating that macrophages require this period for intracellular delivery of liposomes from the cell surface to lysosomes. Measurement of the intraendosomal pH change in a single macrophage at 37 degrees C with liposomes containing a pH-sensitive fluorescent marker, HPTS, showed that the pH value decreased continuously to a constant value of 5.5 in 30-40 min after endocytosis, and this decrease was reversed on addition of NH4Cl, suggesting that acidification of endosomes is not a stepwise reaction and is coupled with delivery of liposomes. These fluorescence microphotometric systems using liposomes containing different fluorescent dyes should be useful for kinetic analyses of the endocytosis and intracellular fate of liposomes in various phagocytes.

Animals↗

An Rsa I polymorphism in the CYP2E1 gene does not affect lung cancer risk in a Japanese population.

CYP2E1 catalyzes the metabolic activation of tobacco-specific N-nitrosamines, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. An Rsa I polymorphism, which is located in the 5'-flanking region of the CYP2E1 gene, has been found to affect the transcriptional regulation of the gene, resulting in different expression levels of the mRNA among individuals. In order to investigate an association between the Rsa I polymorphism and lung cancer susceptibility, the genotype distribution among 316 lung cancer patients was compared with that in 503 healthy controls. No statistically significant association was found between the Rsa I polymorphism and an increased risk of lung cancer, even though histological types of lung cancer, cigarette smoking and alcohol consumption were taken into account.

Cytochrome P-450 CYP2E1↗

Double determinant immuno-polymerase chain reaction: a sensitive method for detecting circulating antigens in human sera.

A sensitive method for the detection of antigens in sera, termed double determinant immunopolymerase chain reaction (double determinant immuno-PCR) was developed, using two monoclonal antibodies (MoAbs), in which the antigens are sandwiched, and a specific DNA molecule is used as a marker. Instead of the antigen itself, the first MoAb to bind the circulating antigens was immobilized. After the biotinylated second MoAb was bound to the antigen, free streptavidin was used to attach a biotinylated DNA to the biotinylated second MoAb. The biotinylated DNA complexed with antigen-antibody-streptavidin was amplified by PCR, and the PCR products were analyzed by Southern blot hybridization after agarose gel electrophoresis. Compared with the conventional enzyme linked immunosorbent assay (ELISA) using soluble intercellular adhesion molecule-1 (sICAM-1) in the supernatant of cultured Panc-1 cells as an antigen, our double determinant immuno-PCR was 10(3) times more sensitive in terms of the detection limit. Not only in culture medium, but also in sera from gastric cancer patients of high sICAM-1 titer, an approximately 10(3)-fold enhancement in detection sensitivity was obtained compared with ELISA. In addition, this system can detect the antigen in sera at a level below the detection limit of traditional ELISA methods with high sensitivity. Thus, double determinant immuno-PCR has the significant advantage that it can be readily applied to any antigen-antibody system for which two MoAbs are available.

Antibodies, Monoclonal↗

Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma.

We have previously shown the elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in patients with bronchial asthma during asthma attacks. In the present study, we extended our earlier study by measuring serum sVCAM-1 levels by ELISA in 45 patients with bronchial asthma (23 atopic and 22 non-atopic) during asthma attacks and in stable conditions in order to assess further the state of adhesion molecules in allergic inflammation of bronchial asthma. The levels of sVCAM-1 in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sVCAM-1 levels, serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. The nature of change in serum TNF-alpha levels correlated with the nature of change in serum sVCAM-1 levels, but serum TNF-alpha levels did not correlate with serum sVCAM-1 levels. These results suggest that higher levels of sVCAM-1 during asthma attacks may reflect the up-regulation of VCAM-1 expression in allergic inflammation, and that a soluble form of VCAM-1 molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of VCAM-1 in vitro, however; the regulatory mechanism in the elevation of serum sVCAM-1 levels remains to be clarified.

Adult↗

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis.

ICAM-1 plays an important role in inflammatory diseases. We analysed ICAM-1 expression on BAL fluid cells and measured soluble ICAM-1 (sICAM-1) concentrations in sera and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar macrophages, and significantly increased values of circulating and BAL fluid sICAM-1 in EAA patients compared with controls. Successive measurement showed prompt decrease of both sICAM-1 values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients, sICAM-1 values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-1 values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar-arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-1 expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-1 in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA.

Adult↗

Epidemiological characteristics of prostate cancer in Gunma Prefecture, Japan. Gunma University Urological Oncology Study Group.

BACKGROUND: Prostate cancer is rare in Asia, but the number of patients is increasing in Japan. We conducted an epidemiological study of prostate cancer in Gunma Prefecture, Japan, to investigate the trends and characteristics of the disease. METHODS: The subjects were 1,411 prostate cancer patients newly diagnosed between 1985 and 1992, and 656 patients who died from prostate cancer between 1981 and 1992. The incidence and mortality rates were calculated by year, demographic region and age. RESULTS: The yearly incidence rate showed an increase but the mortality rate showed no marked fluctuations. There was no significant difference between urban and rural districts in either incidence or mortality rate. The incidence rate tended to be high in the northern part of the prefecture, but no marked variation in mortality rate was seen. The incidence and mortality rates in districts with a history of manganese mining were high compared to those in districts without mining. In contrast, the incidence and mortality rates in districts with a history of zinc mining were comparatively lower. Both incidence and mortality rates showed a marked increase with age. The age-specific incidence showed a double logarithmic relationship to age. CONCLUSIONS: The increase of the yearly incidence rate might be due to changes in lifestyle and environmental factors, improved diagnostic techniques, and increased awareness among the general public regarding prostate disease. Further investigation is needed to clarify the pattern and the causes of regional differences in the incidence and mortality rates. The possibilities that managanese and zinc might be related to prostatic carcinogenesis are suggested.

Age Distribution↗

Prostate-specific antigen in mass screening for carcinoma of the prostate.

BACKGROUND: Prostate-specific antigen (PSA) has various advantages over prostatic acid phosphatase (PAP) as a marker for prostate cancer, but its role in prostate cancer mass screening remains controversial. We measured serum PSA in addition to serum PAP determination and digital rectal examination (DRE) in our mass screening program to assess the usefulness of PSA for prostate cancer mass screening. METHODS: Serum PSA and PAP measurements and DRE were performed in 1249 patients in mass screening for carcinoma of the prostate in 1989 and 1990. Thirteen cancers were diagnosed. We calculated the mean plus standard deviations (2SD) of the PSA and PAP values of men without cancer, and assessed the usefulness of PSA for prostate cancer screening by using these figures as the upper limit of normal. RESULTS: The number positive for PSA, PAP and DRE were 39, 36 and 48, respectively. If our screening had been performed without DRE, three cancers would have remained undetected, and the number would have been the same if performed without PSA. If the screening had been performed without PAP, on the other hand, no cancers would have remained undetected. The sensitivities of PSA and PAP were 54% and 23%, respectively. The screening detection rate with DRE and PSA was 0.88%, and with DRE and PAP was 0.64%. CONCLUSIONS: Measurement of serum PSA values with adjustment of the cut-off value was considered more useful than PAP in mass screening for prostate cancer.

Acid Phosphatase↗

Bilateral painful epileptic seizures of the hands.

Secondary sensory seizures (SSS) are very rare epileptic seizures. A 14-year-old male patient with habitual painful seizures of the backs of both hands since the age of four is reported. The painful seizures were rarely followed by impairment of consciousness. Ictal EEG showed 4 to 6Hz rhythmic waves over the right anterior and mid-temporal area following complaints of pain. The absence of tumorous lesions on brain CT or MRI, childhood onset and the absence of combined seizures were characteristic features of this case compared with other patients reported to have SSS.

Brain↗