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Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 793 records · Page 44Linked to original sources

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

ICAM-1 plays an important role in inflammatory diseases. To assess level of soluble ICAM-1 in the circulation and inflamed lesions, we measured levels of soluble ICAM-1 in the circulation and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and with pulmonary sarcoidosis (PS) and of healthy volunteers (HV), and we also analysed ICAM-1 expression of BALF cells in some patients and HV. IPF patients had significantly higher levels of circulating ICAM-1 than HV, while PS patients did not. By contrast, significantly increased levels of BALF soluble ICAM-1 were found in PS patients compared with those of HV, but not in IPF patients. There were no significant differences in the proportions of ICAM-1+ BALF lymphocytes in IPF patients, PS patients and HV, whereas significantly increased proportions of ICAM-1+ pulmonary alveolar macrophages were found in PS patients compared with those of HV, but not in IPF patients. There was a significant positive correlation of BALF soluble ICAM-1 levels to BALF lymphocyte proportions in PS patients. Although the source of BALF soluble ICAM-1 is unclear, BALF soluble ICAM-1 appears to reflect the grade of local activity of sarcoidosis. An interesting discrepancy between soluble ICAM-1 levels in the circulation and BALF was found in IPF patients, and this might be an important clue to an understanding of this disorder.

Adolescent↗

Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels 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 sICAM-1 and sE-selectin levels, serum tumour 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. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.

Acute Disease↗

Significance of erbB-2 gene product as a target molecule for cancer therapy.

The new monoclonal antibodies (MoAbs) E401, E811, E907 and E919 were prepared and characterized. These recognized an extracellular domain (amino acids No. 292-370) on the human c-erbB-2 gene product. Utilizing MoAb E811 and MoAb E919, a double determinant immunoassay (DDIA) was established to detect the soluble and the shed forms of the c-erbB-2 molecule. The levels of circulating erbB-2 antigen in the sera of patients with benign diseases and healthy controls were very low. The incidence of positivity for shed c-erbB-2 antigen in gastric cancer, colonic cancer, gall-bladder cancer, pancreatic cancer and other cancers were 7.4%, 4.2%, 0%, 6.7% and 0%, respectively. Four of 54 patients with gastric carcinoma showed high levels of serum c-erbB-2 antigen. They belonged to clinical stage IV and their histological types were all well differentiated adenocarcinomas (two papillary and two tubular adenocarcinomas). Furthermore, the incidence of positive staining in gastric cancer was 34.6%; higher than that for shedding erbB-2 antigen. Most of the cases which showed erbB-2 expression on cells were well-differentiated adenocarcinomas. Meanwhile, the distribution of erbB-2 antigen was limited in normal tissues. The results suggest that the expression of erbB-2 antigen is largely restricted to adenocarcinoma cells. It may not shed easily from these cells, and therefore it may be a very useful target molecule for passive immunotherapy.

3T3 Cells↗

Thermal damage to normal and hyperplastic prostates due to transurethral balloon laser therapy in dogs.

Fourteen dogs were studied to determine the level of thermal damage to the normal or benign hyperplastic prostate. Prostates were heated transurethrally by a balloon laser probe (Nd: YAG laser) at various temperatures for 20 min. Coagulative necrosis was observed in the prostate when it was heated above 45.4 degrees C for 20 min. Tissue damage in the bladder neck occurred above 49.4 degrees C, damage to the urethral mucosa occurred above 46.5 degrees C, and damage to the urethral sphincter occurred above 43.2 degrees C. It was calculated that there was a 50% probability of necrosis of the prostate gland occurring when prostatic tissue was treated at 45.0 degrees C for 20 min. Striated muscle cells in the urethral sphincter were more heat-sensitive than smooth muscle cells of the bladder neck or transitional cells of the urethral mucosa. This basic information is essential for the safe application of Nd: YAG laser hyperthermia to the prostate gland.

Animals↗

A comparison of prostate cancer patients in Japan and the USA.

Clinical characteristics of prostate cancer patients were analyzed to compare the rates of progression of prostate cancer between patients in Japan (Gunma Urological Oncology Study Group: GUOSG) and the USA (Roswell Park Cancer Institute: RPCI), between 1980 and 1989. The stage of disease was more advanced and the age was greater in GUOSG patients compared with RPCI patients. However, the prostate cancer death rate of stage D patients at RPCI was significantly higher than that of the GUOSG. Moreover, the survival rate of stage A patients in the GUOSG was better than that of RPCI patients. The possibility of biases which may affect both the clinical characteristics and survival rates in the 2 populations studied is discussed. To determine whether there is a real difference in the rate of prostate cancer growth between the 2 countries will require a prospective study, ideally conducted in large population groups.

Age Distribution↗

A new monoclonal antibody (POG-1) detects a differentiation antigen of porcine granulosa and thecal cells and indicates heterogeneity of thecal-stromal cells.

To identify the differentiation antigen of ovarian cells, we raised a murine monoclonal antibody (POG-1 antibody) reactive to porcine granulosa and thecal cells in the ovary. Immunofluorescence staining showed that expression of the POG-1 antigen on granulosa and theca interna cells increased gradually in accordance with follicular development. The thecal cells just outside the basal lamina surrounding the follicles did not express the antigen, whereas some stromal cells around the theca externa layer in the large follicles did express it. These expression profiles indicated the heterogeneity of thecal-stromal cells and that the POG-1 antigen was a differentiation-related antigen of granulosa and thecal cells. Luteal cells also expressed the antigen. In organs other than the ovary, some endocrine and exocrine cells, such as Leydig cells and secretory cells of the breast, expressed the antigen. The POG-1 antigen was purified from granulosa cells by immunoaffinity chromatography. Polyacrylamide gel electrophoresis profiles showed that the antigen consisted of two specific proteins; the major one had a molecular mass of 77, and the other had a molecular mass of 81 kilodaltons. Analysis of the purified POG-1 antigen may contribute to understanding the differentiation mechanism of granulosa and thecal cells.

Animals↗

Androgens induce prolactin production by human endometrial stromal cells in vitro.

Although there is a significant quantity of androgens in the endometrium, the function of these hormones has not been clarified, except for being estrogen precursors. Human endometrial stromal cells (ESC) were cultured in the presence of testosterone (T) and 5 alpha-dihydrotestosterone. Following culture, prolactin (PRL), a biochemical marker of stromal cell differentiation (decidualization) which is produced by ESC, was examined. T induced PRL production in a time- and dose-dependent manner, as reported previously for progesterone (P) stimulation. In addition, 5 alpha-dihydrotestosterone, which cannot be converted to estrogens, similarly induced PRL production. T in combination with P enhanced PRL production in cultured ESC significantly more than either P or T stimulation alone. A specific androgen receptor blocker, flutamide, when added to cultures containing T, inhibited PRL production in a dose-dependent manner, but did not affect the production of PRL induced by P. These results indicate that in vitro PRL production by human ESC is induced not only by P, but also by androgens through specific receptors and further suggest that androgens play an important role in human endometrial differentiation.

Adult↗

Bestatin, a potent aminopeptidase-N inhibitor, inhibits in vitro decidualization of human endometrial stromal cells.

We have reported that human endometrial stromal cells (ESC) express a cluster of differentiation-13 antigen/aminopeptidase-N, and the expression of this peptidase antigen was shown to increase with the decidualization of ESC. To clarify the role of this peptidase in human endometrium, the effect of bestatin ([(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-(S)-leucine), an inhibitor of aminopeptidase-N, on the decidualization of ESC in vitro was examined. Purified human ESC were cultured for 12 days in the presence of 10(-6) mol/L progesterone with or without bestatin. Decidualization was assessed by PRL production and morphological transformation. The effects of a stereoisomer of bestatin and of pepstatin were similarly examined using the same culture system. Bestatin inhibited progesterone-induced PRL production in a dose-dependent manner, with no effect on cell number or viability, whereas neither its stereoisomer nor pepstatin inhibited aminopeptidase activity or PRL production. The morphological transformation of ESC was also inhibited by bestatin, but not by its stereoisomer or pepstatin. These findings demonstrate that the inhibition of aminopeptidase-N activity blocks the in vitro decidualization of ESC and suggest an important role for this peptidase in the functional differentiation of human ESC.

Adult↗

Progesterone-dependent secretion of macrophage colony-stimulating factor by human endometrial stromal cells of nonpregnant uterus in culture.

Recent studies have suggested that macrophages colony-stimulating factor (M-CSF), a hematopoietic glycoprotein essential to the proliferation and differentiation of mononuclear phagocytes and their progenitor cells, is also involved in the reproductive process in mice and humans. In this study, we examined, by enzyme-linked immunosorbent assay, the supernatants of stromal cell-enriched fraction (SF) of human nonpregnant endometrium for the presence of M-CSF during culture with progesterone (P) or estrogen. The bioactivity of M-CSF was assessed in a colony-forming assay of murine bone marrow cells. In addition, the M-CSF level in the culture supernatant of SF further purified by subculture, of epithelial cell-enriched fraction purified from human endometrium, and of peripheral blood lymphocytes, including about 10% monocytes, was examined with or without P, because SF is contaminated by epithelial cells and macrophages, both of which are suggested to secrete M-CSF. During 2-week culture, the level of M-CSF in the supernatants of SF cultured with P was markedly higher than that of control culture and estrogen-treated culture on any day tested, except for the first 2 days. P had a dose-dependent effect on M-CSF production by SF. Estrogen also enhanced M-CSF production by SF, but did not show dose dependency. The SF culture supernatants showed a colony-forming activity that was completely blocked by neutralizing anti-M-CSF antibody. SF subcultured three times, which was confirmed to be of more than 99% purity, secreted M-CSF in a P-dependent manner. M-CSF was also detected in the culture supernatants of epithelial cell-enriched fraction and peripheral blood lymphocytes, but P-dependent M-CSF production was not shown in these cultures. These results suggest that human endometrial stromal cells themselves can secrete bioactive M-CSF in a P-dependent manner in vitro, indicating that the M-CSF reported to be present in human endometrium is secreted in part by stromal cells and may play a role in the regulation of endometrial function under P control.

Adult↗

Cytokines stimulate dipeptidyl peptidase-IV expression on human luteinizing granulosa cells.

We have previously reported that dipeptidyl peptidase-IV (DPPIV) is a differentiation antigen for human granulosa cells that is initially expressed during corpus luteum formation. To investigate the involvement of cytokines in luteal cell differentiation, we examined the expression and activity of DPPIV in human luteinizing granulosa cells cultured in vitro. Human granulosa cells obtained from patients who had undergone in vitro fertilization were cultured for 7 days in the absence (controls) or presence of hCG (1 U/mL), tumor necrosis factor-alpha (TNF alpha; 10 ng/mL), or interleukin 1-alpha (IL-1 alpha; 10 ng/mL). Flow cytometry showed that the percentage of cultured granulosa cells treated with TNF alpha and IL-1 alpha that was positive for DPPIV expression was significantly higher than that in controls (43.7 +/- 5.4% and 43.4 +/- 5.6%, respectively, vs. 21.7 +/- 3.5%; P < 0.01), whereas hCG treatment produced no remarkable difference in DPPIV expression (24.0 +/- 5.2%). The DPPIV activity of cells treated with TNF alpha and IL-1 alpha was also significantly higher than that of controls, whereas hCG treatment produced no significant difference from control values. These findings indicate that TNF alpha and IL-1 alpha stimulate DPPIV expression and activity in human luteinizing granulosa cells in vitro and suggest the involvement of cytokines in the differentiation of granulosa cells during corpus luteum formation.

Adult↗

Relation between blood pressure and plasma catecholamine concentration after administration of calcium antagonists to rats.

Three types of calcium antagonists, diltiazem, verapamil and nicardipine, were separately infused into Sprague-Dawley (SD) rats (under pentobarbital anesthesia n = 5) through the left femoral vein at four different flow rates. Mean arterial blood pressure, heart rate and the concentration of plasma catecholamines (CAs), epinephrine (E), norepinephrine (NE) and dopamine (DA), were measured for each calcium antagonist, and the correlations between them were studied. Blood samples were collected within the infusion from common jugular vein. Plasma concentrations of CAs were determined by a HPLC-ethylenediamine condensation reaction-peroxyoxalate chemiluminescence detection system (HPLC-ED-PO-CL). The plasma concentration of CAs increased corresponding to the blood pressure reduction. The reduction induced by each calcium antagonist correlated with the logarithm of plasma NE concentration. The relation was expressed as Y = -alpha log X+m (Y, blood pressure; X, concentration of plasma NE; alpha, slope; and m, intercept). The correlation coefficients (rs) were -0.950 (diltiazem), -0.975 (verapamil) and -0.978 (nicardipine) (versus -0.734 for control). The alpha for nicardipine (108.4) was greater than those of diltiazem (85.4) and verapamil (80.8) (versus 31.0 for control), meaning that blood pressure reduction was greater in the case of nicardipine than diltiazem and verapamil, with an identical increment of plasma NE concentration. These data indicate that the contribution of the sympathetic nervous system to maintaining blood pressure reduced by nicardipine is less than that observed following the infusion of diltiazem and verapamil. Similar good inverse correlations between blood pressure and the logarithm of plasma concentration of E were observed with the three drugs infused (r = -0.928, -0.966, and -0.948 for diltiazem, verapmil and nicardipine, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Antioxidative effect of mammalian liver hydrolyzate on lipid peroxidation].

The antioxidative effect of the mammalian liver hydrolyzate preparation (LH) was investigated mainly in the mouse liver homogenates. At lower concentrations, LH stimulated lipid peroxidation induced by Fe2+ and ascorbic acid in the homogenates, but inhibited completely the oxidation at higher concentrations. LH also inhibited the peroxidation of linolenic acid and linoleic acid. LH reduced 1,1-diphenyl-2-picrylhydrazyl, a free radical model, in a concentration-dependent manner, suggesting that the radical scavenging property of LH is involved in its antioxidative action. Fe2+ and glutathione, contained in LH, seem to act as a stimulator and an inhibitor of peroxidation, respectively.

Animals↗

[In vitro cell proliferation assay method using rat gastric cultured cells and effect of anti-ulcer drugs on the proliferation of cultured cells].

In order to establish a rapid and accurate in vitro drug assay method, we have applied the avidin D-biotin complex enzyme-linked immunosorbent assay using 5-bromodeoxyuridine (BrdU-ELISA) in the microplate cultures. To study the rat gastric cell proliferation, BrdU was treated with the cultured cells, and then, the rate of the uptake of BrdU into the cells was measured using an anti-BrdU antibody. Prostaglandin E2 (PGE2) (0.01, 0.1 and 1 microM), cimetidine (1, 3 and 10 microM) and omeprazole (3 and 10 microM) were shown to induce the significant proliferation of rat gastric cultured cells. Indomethacin (IND) (0.1, 0.25 and 0.5 mM) caused a dose-dependent inhibition of the proliferation of the cultured cells proliferation. The result obtained by the BrdU-ELISA method was more reproducible than that by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. PGE2 (0.01, 0.1 and 1 microM), cimetidine (1, 3 and 10 microM), omeprazole (1, 3 and 10 microM), cetraxate (3, 10 and 30 microM) and famotidine (30 microM), but not sofalcone and NC-1300-O-3, have been shown to protect significantly rat gastric cultured cells against IND-induced damage in vitro. From these results, it might be suggested that this BrdU-ELISA method is useful for investigating the effect of drugs on the proliferation of rat gastric cultured cells.

Animals↗

Ventricular unloading and improvement in left ventricular function after angiotensin converting enzyme inhibition with enalapril in patients with chronic congestive heart failure.

To clarify how angiotensin converting enzyme inhibition affects left ventricular function through ventricular unloading, ventricular wall stress, ventricular volumes, and other cardiac indices and exercise tolerance were evaluated in 17 patients with mild to moderate chronic congestive heart failure before and after 3 months of treatment with enalapril. Echocardiographic examination revealed that treatment with this angiotensin converting enzyme inhibitor resulted in significant reductions in end-systolic wall stress (117 +/- 25 to 89 +/- 28 g/cm2, p < 0.01) and left ventricular volume indices (end-diastolic: 163 +/- 56 to 143 +/- 60; end-systolic 99 +/- 51 to 77 +/- 57 ml/m2 p < 0.01). Ejection fraction (42 +/- 11 to 48 +/- 13%, p < 0.01) and systolic blood pressure/end-systolic volume (SBP/ESV; 1.06 +/- 0.30 to 1.33 +/- 0.48 mmHg/ml, p < 0.01) were both increased. By radionuclide ventriculography, ejection fraction and peak ejection rate (2.30 +/- 0.74 to 2.80 +/- 0.76 EDV/sec, p < 0.01) were increased, while time to peak ejection, time to peak filling, and peak filling rate were unchanged. Heart rate and double product at exercise were decreased and delta EF was significantly increased (-1.4 +/- 4.1 to 1.6 +/- 4.4%, p < 0.02). The decrease in end-systolic wall stress was consistently related to both the increase in ejection fraction and SBP/ESV, while the decrease in end-diastolic volume was related only to SBP/ESV and not to ejection fraction. Furthermore, there was a direct relationship between the decrease in systolic wall stress and the decrease in end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improvement of multiple coronary risk factors in obese hypertensives by reduction of intra-abdominal visceral fat.

The association of obesity and hypertension is well documented, and the combination is important as a coronary risk factor, but its non-pharmacological management is very difficult. Japanese hypertensive obese subjects (HO, n = 95) selected from 321 non-medicated obese subjects with a body mass index > 25 kg/m2 were characterized by the clinical features of significant diaphragmatic elevation, higher heart rate (HR), fasting blood glucose (FBS), total cholesterol (Tch), uric acid and gamma GTP values and lower vital capacity (VC) compared to those of normotensive-obese subjects (NO, n = 226) (p < 0.01). During a diet therapy program (about 1,200 kcal/day) for HO (n = 55), 25 subjects were treated with a non-drug-dependent pulse-synchronized transpercutaneous electric abdominal muscle stimulator (PEM) (ca. 30,000 muscle contractions/day) for 4 weeks. These subjects showed significant improvement with reduction in body weight (9.4%, 7.4 kg), intra-abdominal visceral fat (VF) CT scan area (29%), abdominal subcutaneous area (10%) at the level of the umbilicus, blood pressure (BP), HR, FBS, gamma GTP, Tch, plasma norepinephrine, plasma renin activity and plasma insulin, an increase of VC and lowering of the diaphragm (p < 0.05). The reductions in weight, BP, FBS and Tch in the diet group (n = 30, 1,200 kcal/day for 4 weeks) were smaller than those in the PEM-diet group (p < 0.05). The Japanese hypertensive obese patients had complications of many other coronary risk factors, and the reduction in weight and VF with PEM-diet therapy seems to be effective for improving these risk factors.

Abdominal Muscles↗

Obstructive sleep apnea attack in complex craniosynostosis.

For treatment of patients with complex craniosynostosis, increased intracranial pressure, severe exophthalmos, and apnea attacks are important indications for operative intervention. Little has been reported on obstructive sleep apnea in complex craniosynostosis. Obstructive sleep apnea attacks in complex craniosynostosis are evaluated in relation to the upper and middle pharyngeal space and to the dimensions of the maxilla and mandible measured on cephalograms. The value of the pharyngeal air space in craniosynostosis had no relationship with either the frequency of sleep apnea attack or with severity of snoring. The dimensions had a close relationship with obstructive sleep apnea attack.

Adolescent↗

Quantitative analysis of soluble cell adhesion molecules in otitis media with effusion.

The levels of the soluble intercellular adhesion molecule 1 (sICAM-1) and soluble granule membrane protein-140 (sGMP-140) were measured in middle ear effusions (MEEs) of otitis media (OM) with ELISA. MEEs of chronic serous and mucoid OM in children contained significantly higher levels of sICAM-1 and sGMP-140 compared with normal serum. sGMP-140 in acute and chronic OM in children was higher than in adult chronic serous OM, and in acute purulent OM higher chronic serous OM in children. Cytologic analysis showed that the mean level of sGMP-140 was significantly higher in the neutrophil dominant group than in other groups except the few cells type. sICAM-1 showed no differences among the cytologic classifications. Copious amounts of sICAM-1 and sGMP-140 in MEEs were observed in this study, and were probably the result of shedding from the cells expressed cell adhesion molecules. These cell adhesion molecules in MEEs were thought to modify the inflammatory response in OM.

Acute Disease↗

Compliance with long-term dietary salt restriction in hypertensive outpatients.

Eighty hypertensive outpatients were recruited for a dietary salt restriction program to examine long-term compliance. Twenty-four-hour urine samples were collected repeatedly (7.9 +/- 2.6 times, mean +/- s.d.) during a follow-up period of 6.4 +/- 1.7 years. After initial urine collection, nutritional education was carried out by dietitians to reduce dietary salt intake to 8 g/day or less. After every urine collection, the subjects were given advice by doctors on salt restriction, if necessary. The mean 24-hour urinary salt excretion (U-NaCl) and the mean urinary salt/creatinine ratio (U-NaCl/U-Cr) varied considerably both among and within individuals. U-NaCl/U-Cr, but not U-NaCl, in females was significantly higher than that in males, and in middle-aged subjects than in young subjects. U-NaCl and U-NaCl/U-Cr tended to decrease in the summer. In spite of the repeated educational effort, neither U-NaCl nor U-NaCl/U-Cr was different in the first control samples from that in the last samples. When 57 subjects were divided into three groups according to the urinary salt excretion level, U-NaCl was consistently higher during a follow-up period in the high-salt excretion group than in the mid-salt excretion group, while U-NaCl in the low-salt excretion group was initially lower than, but finally similar to, that in the mid-salt excretion group. These results suggest that: (1) multiple 24-hour urine samplings are required to assess urinary salt excretion in individuals; (2) the influence of age and sex should be taken into account in interpreting U-NaCl/U-Cr; and (3) it seems difficult to achieve long-term dietary salt restriction as a non-pharmacologic treatment of hypertension in an outpatient clinic.

Adult↗