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Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 811 records · Page 45Linked to original sources

Phorbol ester stimulates PAF synthesis via the activation of protein kinase C in rat leukocytes.

When rat pleural mononuclear leukocytes were stimulated with 1 microM phorbol myristate acetate (PMA), platelet-activating factor (PAF)-like activity was detected in the supernatant and the cellular fractions of the incubation mixture, as measured by rabbit platelet aggregation. C16PAF activity peaked at 30 min in both fractions. Acetyltransferase activity in the microsomal fraction of the stimulated cells also increased rapidly and showed a peak at 10 min. A protein kinase C inhibitor, staurosporine, and an inhibitor of phospholipase A2, p-bromophen-acylbromide, inhibited stimulated PAF formation in both fractions. Staurosporine also inhibited PMA induced acetyltransferase activity. The data suggest that PMA stimulates PAF synthesis by the remodeling pathway in rat pleural cells through activation of both phospholipase A2 and acetyltransferase, and that the acetyltransferase, in turn, may be activated through activation of protein kinase C.

Acetyltransferases↗

Involvement of platelet-activating factor in zymosan-induced rat pleurisy.

The role of platelet-activating factor (PAF) in inflammatory reactions was studied in zymosan-induced rat pleurisy. Pleurisy was induced by injection of a 2% zymosan suspension into the pleural cavity of rats. The time course of pleural exudate accumulation, the exudation rate, and exudate leukocyte numbers were followed then for 96 hr. Peak pleural exudate accumulation was about 3 mL at 24 hr, whereas the exudation rate increased biphasically with peaks at 0.5 hr and 5 hr. The migration of leukocytes into the pleural cavity increased with time up to 48 hr. The polymorphonuclear leukocytes were the dominant white cells in the exudate between 5 and 16 hr, but mononuclear leukocytes started to outnumber them around 24 hr. Pretreatment with cyproheptadine (5 mg/kg), an inhibitor of both histamine and serotonin, significantly suppressed pleural fluid accumulation and the exudation rate at 0.5 hr. The PAF antagonist CV-6209 (1 mg/kg) significantly suppressed pleural fluid accumulation and the exudation rate at both 0.5 and 5 hr. At either time point, the parameters were not suppressed by indomethacin. We detected PAF activity in the high-performance liquid chromatography (HPLC) fraction (with a retention time corresponding to that of authentic PAF) of the exudates at 0.5 hr, 5 hr, and 16 hr using an aggregation bioassay with washed rabbit platelets. The results suggest that in zymosan-induced rat pleurisy, histamine and/or serotonin are the main mediators of exudation at 0.5 hr and that PAF may be partly responsible for exudation at 0.5 hr and later at 5 hr to 16 hr.

Animals↗

A case of intestinal T-cell lymphoma with repeated episodes of perforation.

A case of intestinal cytotoxic/suppressor T-cell lymphoma with repeated episodes of perforation was seen in a 77-year-old Japanese male who was admitted complaining of severe abdominal pain accompanied by high grade fever. Surgery revealed diffuse peritonitis due to perforation in the sigmoid colon. After a loop sigmoid colostomy the patient recovered to some degree. Seven days later, however, another perforation occurred. Several aneurysmal swellings accompanied by perforation in the small intestine, forming a mass of 5 x 5 cm, were seen. Although the patient tolerated this operation, generalized emaciation proceeded and the patient died 10 days late. Histological examination at the second operation showed diffuse medium-sized lymphoma of the Lymphoma Study Group (LSG) classification infiltrating the entire depth of the intestinal wall. Destruction of muscle cells was prominent. An immunohistochemical study using fresh frozen material was positive for CD3, and CD8. This marked destruction of the muscle layer by lymphoma cells may be associated with repeated episodes of perforation.

Aged↗

Palliative repair of aortic atresia associated with tricuspid atresia and transposition of the great arteries.

Successful palliative repair of aortic atresia and hypoplastic aortic arch associated with tricuspid atresia in a neonate is described. The repair consisted of reconstruction of the hypoplastic aortic arch with an equine pericardial patch, division of the patient ductus arteriosus, connection of the pulmonary artery to the aorta, implantation of the proximal part of the ascending aorta into the main pulmonary artery, and anastomosis of a polytetrafluoroethylene graft 5 mm in diameter between the right ventricular outflow tract and the central pulmonary artery, which was transferred anteriorly to the main pulmonary artery.

Abnormalities, Multiple↗

Ultrasonic tissue characterization of chronic liver disease using cepstral analysis.

To evaluate the morphological changes in chronic liver disease by means of ultrasonography, cepstral analysis was applied to the ultrasonic waveforms obtained with a 10-MHz transducer during peritoneoscopy. Assuming that liver tissue was a collection of semiregularly arrayed small scatters of ultrasound, the spaces between scatterers of the liver could be measured by means of cepstral analysis. From the distribution of the spaces between scatterers, two statistical parameters, mode and kurtosis, were determined for each patient. The mode of spaces between scatterers for liver cirrhosis was significantly larger than that for chronic hepatitis and nonspecific change. The mode of spaces between scatterers was correlated with the size of hepatic lobules or nodules. The kurtosis of spaces between scatterers for chronic hepatitis and liver cirrhosis was significantly smaller than that for nonspecific change. As a preliminary study for noninvasive application of this technique, cepstral analysis was also applied to the ultrasonogram obtained through the abdominal wall with a 3.5-MHz transducer. The results obtained with a 3.5-MHz transducer were correlated well with those obtained with a 10-MHz transducer. These results suggest the possibility of noninvasive evaluation of the structural changes in chronic liver disease.

Chronic Disease↗

Serotonin inhibits release of substance P evoked by tooth pulp stimulation in trigeminal nucleus caudalis in rabbits.

The influence of the serotonin (5-HT) system on the release of immunoreactive substance P after electrical stimulation of the lower incisor pulp was examined by perfusion of the superficial layers of the subnucleus caudalis of the brain stem trigeminal sensory nuclear complex of rabbits in situ. Increased release of immunoreactive substance P was observed after electrical stimulation of the pulp at 40 V. Stimulation of the nucleus raphe magnus significantly increased the release of 5-HT and completely inhibited the release of immunoreactive substance P, evoked by stimulation of the tooth pulp. Local application of 5-HT (10(-6) M) inhibited the release of immunoreactive substance P induced by stimulation and this inhibition was antagonized by methysergide (10(-4) M) applied concomitantly to the superficial layers of the trigeminal nucleus. These results suggest a functional interaction between substance P and 5-HT in the superficial layers of the trigeminal nucleus for regulation of transmission of dental pain.

Animals↗

Effects of continuous infusion of parathyroid hormone and parathyroid hormone-related peptide on rat bone in vivo: comparative study by histomorphometry.

We have investigated the actions of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) on the bones of parathyroidectomized (PTX) rats by histomorphometric analysis. Miniosmotic pumps filled with either human PTH (hPTH)(1-34), hPTHrP(1-34) or vehicle were subcutaneously implanted on the backs of the rats. The peptides were continuously infused for 6 days at a rate of 15 nmole/kg/day. PTH and PTHrP exhibited similar hypercalcemic and hypophosphatemic actions on these PTX rats. No significant differences were noted in bone weight or calcium and phosphorus contents of the ashed bone among the 3 groups. By quantitative histomorphometric analysis, hPTH(1-34) and hPTHrP(1-34) were found similarly to enhance both bone formation and resorption. Peritrabecular fibrosis was observed only in the PTH-infused animals. PTHrP thus mimics the actions of PTH, but is not as effective in promoting mesenchymal cell proliferation along the bone trabeculae.

Animals↗

Neurotropin inhibits experimental allergic encephalomyelitis (EAE) in Lewis rats.

The effects of Neurotropin, a substance extracted from the inflammatory dermis of rabbits inoculated with Vaccinia virus, for experimental allergic encephalomyelitis (EAE) in Lewis rats, a model for human multiple sclerosis (MS), was studied. The peptide defined by residues 68-84 (MB 68-84) which corresponds to the encephalitogenic portion of the guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra (CFA) was injected into the hind foot pad of each rat. Neurotropin significantly suppressed the clinical and histological expression of actively induced EAE when administered i.p. daily from day 0 to day 6 after immunization. In addition, passive EAE induced by precultured spleen cells from rats immunized with MB 68-84 in CFA was also suppressed by daily administration of Neurotropin after cell transfer. Neurotropin treatment significantly suppressed the delayed-type hypersensitivity (DTH) response to MB 68-84. Furthermore, the ability of spleen cells from Neurotropin-treated rats to transfer EAE was significantly lower than that of saline-treated rats. It seemed that the suppression may be due to the inhibition of the activation by MB 68-84 of sensitized spleen cells, as demonstrated by proliferative response to MB 68-84. However, no difference was observed in Con A-induced proliferative response of the spleen cells between Neurotropin- and saline-treated rats. These findings indicate that Neurotropin inhibits EAE by suppressing the immune responses to encephalitogenic MBP with little non-specific suppression.

Animals↗

Identification of a carbohydrate-based endothelial ligand for a lymphocyte homing receptor.

Lymphocyte attachment to high endothelial venules within lymph nodes is mediated by the peripheral lymph node homing receptor (pnHR), originally defined on mouse lymphocytes by the MEL-14 mAb. The pnHR is a calcium-dependent lectin-like receptor, a member of the LEC-CAM family of adhesion proteins. Here, using a soluble recombinant form of the homing receptor, we have identified an endothelial ligand for the pnHR as an approximately 50-kD sulfated, fucosylated, and sialylated glycoprotein, which we designate Sgp50 (sulfated glycoprotein of 50 kD). Recombinant receptor binding to this lymph node-specific glycoprotein requires calcium and is inhibitable by specific carbohydrates and by MEL-14 mAb. Sialylation of the component is required for binding. Additionally, the glycoprotein is precipitated by MECA-79, an adhesion-blocking mAb reactive with lymph node HEV. A related glycoprotein of approximately 90 kD (designated as Sgp90) is also identified.

Animals↗

The complement binding-like domains of the murine homing receptor facilitate lectin activity.

The leukocyte homing receptor (HR), the endothelial leukocyte adhesion molecule, and gmp140/platelet activation-dependent granule membrane protein are members of a family of adhesion molecules, termed the lectin cell adhesion molecules (LEC-CAMS) which are unified by a multi-domain structure containing a lectin motif, an epidermal growth factor-like (egf) motif, and variable numbers of a complement binding-like (CB) motif. Previous data have indicated a predominant role for the lectin motif in cell adhesion directed by the LEC-CAMS, although the egf-like domain of the HR may also play a potential role in cell binding. While the role(s) of the CB domains in the LEC-CAMS is currently not understood, they have been hypothesized to act as rigid spacers or stalks for lectin and perhaps, egf domain presentation. In this paper, we analyze the functional characteristics of murine HR-IgG chimeras containing the lectin, lectin plus egf, and lectin plus egf plus CB domains. The Mel 14 mAb, an adhesion blocking antibody which recognizes a conformational determinant in the N-terminus of the HR lectin domain, shows a significantly decreased affinity for a HR construct which lacks the CB motifs, consistent with the possibility that the CB domains are involved with lectin domain structure. In agreement with this conjecture, HR mutants lacking the CB domains show a profound decrease in lectin-specific interaction with the carbohydrate polyphosphomannan ester, suggesting that the changes in Mel 14 affinity for the lectin domain are reflected in lectin functionality. Various assays investigating the interactions between the HR deletion mutants and the peripheral lymph node high endothelium, including cell blocking, immunohistochemical staining, and radioactively labeled ligand binding, all showed that removal of the CB domains results in a lack of HR adhesive function. These results imply that the CB domains of the HR, and, by analogy, the other members of the LEC-CAM family, may play important structural roles involving induction of lectin domain conformation and resultant functionality.

Antibodies, Monoclonal↗

Nitrogenous ligation at the sixth coordination position of the Thr-301 to Lys-mutated P450IIC2 heme iron.

Threonine-301 of P450IIC2 was replaced by lysine via site-directed mutagenesis. The Lys-mutated P450 exhibited absorption spectra that were characteristic of the nitrogenous-ligand-bound form of P450. In the oxidized form, the Soret band was red-shifted as compared with the typical ferric low-spin form of P450 and the beta band was more intense than the alpha band. In the reduced form, two Soret peaks were observable at 447 and 423 nm and their relative heights were dependent on pH, indicating the existence of two interconvertible states of ferrous Lys-mutated P450 which are in equilibrium. In addition, the interaction of external ligands with the P450 heme iron was profoundly inhibited both in the oxidized and reduced forms. These findings suggest that epsilon-amino nitrogen of Lys-301, which was introduced by amino acid substitution, occupies the 6th coordination position with the heme iron of the Lys-mutated P450, because, owing to conformation of the P450 protein, the epsilon-amino group may be located at just the right position for coordination as the internal 6th ligand.

Base Sequence↗

Assessment of age-dependent changes in circadian blood pressure rhythm in patients with essential hypertension.

The effects of age on the circadian blood pressure rhythm of patients with untreated essential hypertension (n = 133, World Health Organization stage I or II) were compared with those of normotensive subjects (n = 91). Subjects were classified into three groups by age: young (less than 40 years old), adult (40-59 years old) and old (greater than or equal to 60 years old). Blood pressure was monitored every 5 min for 24 h, using a finger volume oscillometric device under fixed external conditions. The single cosinor method was used to evaluate circadian rhythm. There was no difference in the amplitude of circadian systolic or diastolic blood pressure rhythm among the different normotensive and essentially hypertensive age groups although a wide distribution of amplitude was noted within each group. The distribution of amplitude was wider in the hypertensive than in the normotensive groups. The amplitude of circadian blood pressure rhythm was independent of the mesor level. On the other hand, the amplitude of circadian heart rate rhythm decreased with increasing age both in normotensive subjects (P less than 0.05, young versus adult or old) and hypertensive patients (P less than 0.01, young and old versus adult). The acrophase of circadian systolic blood pressure rhythm in young hypertensives was greater than that in adult or old hypertensives (P less than 0.05, for both). Such age-dependent changes were not observed in the normotensive groups. Consequently, the acrophase of circadian systolic or diastolic blood pressure rhythm in young hypertensives was larger than that in young normotensives (P less than 0.05, for both systolic and diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of the Serratia marcescens proBA operon and feedback control of proline biosynthesis.

The proBA operon, coding for gamma-glutamyl kinase (GK) and gamma-glutamyl phosphate reductase (GPR), was cloned from the chromosome of the wild-type strain of Serratia marcescens Sr41. From our sequence data the proB (1101 bp) and proA (1472 bp) genes were shown to code for two proteins of Mr 39,169 and 44,640, respectively. Analysis of expression of the lacZ structural gene fused with the proBA promoter showed that the proBA operon is not subject to proline-mediated feedback repression. Amplification of the proBA operon enabled us to determine GK activity, which was inhibited in the presence of a low concentration of L-proline. Comparison of the amino acid sequences of the S. marcescens GK and GPR proteins with those of the GK and GPR proteins from E. coli revealed extensive similarities.

Aldehyde Oxidoreductases↗

Effects of recombinant interleukin 4 on the growth and differentiation of blast progenitors stimulated with G-CSF, GM-CSF and IL-3 from acute myeloblastic leukaemia patients.

The effects of human recombinant interleukin 4 (rIL-4) on the growth of leukaemic blast progenitors were investigated. Cells obtained from 20 acute myeloblastic leukaemia (AML) patients were evaluated using the blast colony assay in methylcellulose and suspension cultures. While rIL-4 by itself did not show any colony stimulatory activity in the blast colony assay, it suppressed the blast colony formation in methylcellulose stimulated with G-CSF, GM-CSF or IL-3 in 14 patients. In another six patients, rIL-4 enhanced blast colony growth in four patients or did not show any significant effect with any CSF in two patients. In suspension cultures of 12 cases studied, the effects of rIL-4 on the clonogenic cell recoveries were essentially similar to the results of the blast colony assay in each case. In three patients, rIL-4 augmented the differentiation of the leukaemic cells to monocyte lineage. Further, the clinical outcome was significantly different between the patients whose blast progenitors were stimulated by rIL-4 and the patients whose blast progenitors were suppressed by rIL-4 (P less than 0.05); three out of four patients in the former group failed in achieving complete remission (CR), while 12 out of 14 patients in the latter group achieved CR. The results show that the effects of IL-4 on leukaemic blast progenitors were diverse and the responsiveness to IL-4 may be correlated with the prognoses of the patients.

Acute Disease↗

Purification and characterization of human papillomavirus type 16 E7 protein with preferential binding capacity to the underphosphorylated form of retinoblastoma gene product.

Human papillomavirus type 16 E7 is considered to be a major viral oncoprotein playing an important role(s) in cervical cancers. E7 protein was shown to bind to the protein product of the retinoblastoma gene (RB), while simian virus 40 large T and adenovirus E1A were also shown to possess binding activity to RB protein. The RB protein is a cell cycle regulator that is highly phosphorylated specifically in S, G2, and M, whereas it is underphosphorylated in G0 and G1. Recently, large T was demonstrated to bind preferentially to the underphosphorylated RB protein, which is considered to be an active form restricting cell proliferation. However, it is not known whether E7 can bind to phosphorylated RB protein. We successfully purified large quantities of unfused human papillomavirus type 16 E7 protein expressed in Escherichia coli by using a T7 promoter-T7 RNA polymerase system. The purified E7 protein was demonstrated to bind preferentially to the underphosphorylated RB protein.

Amino Acid Sequence↗

Identification of a GTPase-activating protein homolog in Schizosaccharomyces pombe.

Loss of function of the Schizosaccharomyces pombe gap1 gene results in the same phenotypes as those caused by an activated ras1 mutation, i.e., hypersensitivity to the mating factor and inability to perform efficient mating. Sequence analysis of gap1 indicates that it encodes a homolog of the mammalian Ras GTPase-activating protein (GAP). The predicted gap1 gene product has 766 amino acids with relatively short N- and C-terminal regions flanking the conserved core sequence of GAP. Genetic analysis suggests that S. pombe Gap1 functions primarily as a negative regulator of Ras1, like S. cerevisiae GAP homologs encoded by IRA1 and IRA2, but is unlikely to be a downstream effector of the Ras protein, a role proposed for mammalian GAP. Thus, Gap1 and Ste6, a putative GDP-GTP-exchanging protein for Ras1 previously identified, appear to play antagonistic roles in the Ras-GTPase cycle in S. pombe. Furthermore, we suggest that this Ras-GTPase cycle involves the ra12 gene product, another positive regulator of Ras1 whose homologs have not been identified in other organisms, which could function either as a second GDP-GTP-exchanging protein or as a factor that negatively regulates Gap1 activity.

Amino Acid Sequence↗

Prostate cancer: local staging with endorectal surface coil MR imaging.

Endorectal surface coil magnetic resonance (MR) imaging was used to stage the local extent of prostate cancer in 22 patients. The endorectal coil images were acquired with a 10-12-cm field of view and a 4-mm section thickness. All pathologic specimens were reviewed by one pathologist. Endorectal surface coil MR imaging was 82% accurate in the differentiation of stage B from stage C cancer. One case was overestimated, and three cases were underestimated. The three underestimated cases consisted of two cases of microscopic capsular invasion and one case of minimal seminal vesicle invasion. In a comparison of retrospective, blinded readings of endorectal coil and body coil images, there was an average improvement in accuracy of 16% in staging prostate cancer with endorectal coil images.

Carcinoma↗

Therapeutic trial of hematological disorders with intermittent administration of high-dose 1-alpha-hydroxyvitamin D3.

Aplastic anemia and myelodysplastic syndrome were successfully treated with an intermittent administration of high-dose 1 alpha-hydroxy-vitamin D3, an active analogue of 1,25-dihydroxyvitamin D3. This effect was considered to be through the differentiation-inducing and immunomodulatory actions of 1,25-dihydroxyvitamin D3. The only adverse effect was hypercalciuria which was controllable by decreasing the dose.

Adult↗