PubMed HealthSearch

Biomedical subjects

M Kawamoto

Publications and source records attributed to M Kawamoto.

At least 19 recordsLinked to original sources

Expression of the SART-1 tumor rejection antigen in breast cancer.

We investigated in breast cancers the expression of the SART-1 gene encoding tumor rejection antigens. SART-1 mRNA was expressed in all of the samples tested. The SART-1(800) antigen was detectable in 20 of 50 (40%) breast cancer tissues and all breast cancer cell lines tested, but not in normal breast tissues. The SART-1(800)+ breast cancer cells transfected with HLA-A2601 or HLA-A2402 cDNA were recognized by the HLA-A26-restricted and SART-1-specific cytotoxic T lymphocytes (CTLs) or the HLA-A24-restricted and SART-1-specific CTLs, respectively. Among the 20 SART-1(800)+ tumors, 9 or 8 tumors expressed estrogen receptor or progesterone receptor, respectively. Therefore, the patients with HLA-A26 or -A24 haplotype might be appropriate candidates for specific immunotherapy with the SART-1 peptides independently or in combination with hormone therapy.

Antigens, Neoplasm

An autocrine or a paracrine role of adrenomedullin in modulating cardiac fibroblast growth.

OBJECTIVE: The aim of the present study was to determine the role of adrenomedullin (AM) in cardiac fibroblasts. METHODS: The production and secretion of AM were examined in cultured neonatal rat cardiac fibroblasts, and the effects of AM on proliferation and protein synthesis of these cells were assessed by [3H]thymidine and [3H]phenylalanine incorporation, respectively. RESULTS: Cultured cardiac fibroblasts secreted AM into the medium time-dependently at a rate of 20.3 +/- 3.0 fmol/5 x 10(4) cells/48 h, mean +/- S.D. Northern blot analysis showed expression of preproAM mRNA of 1.6 kb in these cells. In addition, 10(-6) mol/l of angiotensin II (Ang II) and endothelin-1 (ET-1) significantly increased the AM secretion by 55 and 48%, respectively. Synthetic AM significantly reduced 10(-6) mol/l Ang II- or 10(-7) mol/l ET-1-stimulated [3H]thymidine and [3H]phenylalanine incorporation in a dose-dependent manner, and these effects were attenuated by a calcitonin gene-related peptide (CGRP) type 1 receptor antagonist, CGRP(8-37). Synthetic AM also had a dose-dependent stimulatory effect on cAMP accumulation in these cells, which was significantly attenuated by CGRP(8-37). A cAMP analogue, 8-bromo-cAMP, mimicked the AM effects, inhibiting the Ang II-stimulated [3H]thymidine and [3H]phenylalanine incorporation. Blockage of the effect of endogenous AM by anti-AM monoclonal antibody not only significantly reduced the basal level of intracellular cAMP, but also enhanced the [3H]thymidine and [3H]phenylalanine incorporation into the cells. CONCLUSIONS: Cultured neonatal rat cardiac fibroblasts produce and secrete AM, and the secreted AM may inhibit proliferation and protein synthesis of these cells. AM may exert these inhibitory effects partly by elevating intracellular cAMP. It is suggested that AM has an important role in modulating the growth of cardiac fibroblasts in an autocrine or a paracrine manner.

8-Bromo Cyclic Adenosine Monophosphate

Plasma and urine levels of adrenomedullin and proadrenomedullin N-terminal 20 peptide in chronic glomerulonephritis.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. We examined the plasma and urinary levels of these peptides in patients with chronic glomerulonephritis (CGN). The mean plasma AM concentration of the patients with CGN did not differ from that of control subjects (4.17 +/- 0.17 v 3.87 +/- 0.21 fmol/mL, respectively), whereas urinary AM excretion was significantly less in the patients with CGN (5.96 +/- 0.95 v control, 8.93 +/- 1.02 fmol/mg of creatinine; P < 0.05). Plasma concentrations and urinary excretion of PAMP were significantly less for the patients with CGN compared with control subjects (0.91 +/- 0.08 v 1.23 +/- 0.20 fmol/mL; P < 0.05 and 25.0 +/- 3.0 v 35.0 +/- 3.6 fmol/mg of creatinine, respectively; P < 0. 05). The plasma AM concentration was negatively correlated with plasma renin activity (r = -0.58; P < 0.01) and aldosterone concentration (r = -0.40; P < 0.05). Urinary excretions of AM and PAMP showed significant correlations with urine excretion of sodium (r = 0.39; P < 0.05 and r = 0.49; P < 0.01, respectively). These findings suggest that AM and PAMP may have roles in the regulation of sodium in patients with CGN.

Adrenomedullin

Outgrowth of pseudopodial cables induced by all-trans retinoic acid in micromere-derived cells isolated from sea urchin embryos.

Cultured cells derived from micromeres of sea urchin embryos underwent pseudopodial cable growth without spicule rod formation in the presence of all-trans retinoic acid (tRA) or insulin. Pseudopodial cable growth caused by tRA or insulin was inhibited by genistein, a protein tyrosine kinase inhibitor. Phosphorylation of protein tyrosine residue was augmented in the cells treated with tRA or insulin and was inhibited by genistein. Probably, protein tyrosine kinase takes an indispensable part in signal transduction systems for tRA and insulin in these cells. In tRA-treated cells, augmentation of the phosphorylation of protein tyrosine residue was accompanied by an increase in the activity of protein tyrosine kinase and was inhibited by actinomycin D, inhibiting cable growth. Activation of this enzyme in tRA-treated cells probably depends on RNA synthesis. In insulin-treated cells, augmentation of tyrosine residue phosphorylation occurred without any appreciable change in this enzyme's activity and was hardly affected by actinomycin D. Phosphorylation of protein tyrosine residue seems to be activated by the binding of insulin to an insulin receptor. Pseudopodial cable growth in these cells treated with tRA or insulin was inhibited by wortmannin. Phosphatidylinositol 3 kinase probably participates in tRA and insulin signal transduction systems.

Animals

Normal in-plane respiratory motion of the bilateral hemidiaphragms evaluated by sequentially subtracted fast magnetic resonance images.

The purpose of this study was to demonstrate hemidiaphragmatic motion using magnetic resonance imaging. The subjects were 13 healthy, nonsmoking volunteers. The sequence consisted of a fast gradient-recalled echo for coronal images and a single-shot fast spin echo with half Fourier transformation for sagittal images. The coronal and sagittal acquisition times were 0.83 msec and 0.58 msec per image, respectively. Thirty sequential images were obtained during quiet, deep respiration. Two series of subtraction images were made from these original sequential images (a given image was subtracted from the preceding or the next image in the original series). Hemidiaphragmatic motion was visualized as white or black bands on subtraction images. In the coronal plane through the left ventricle, there was a difference in motion between the right and left hemidiaphragms in 10 subjects during tidal respiration and in 12 subjects during deep respiration. On the sagittal images, the dorsal part of the hemidiaphragm moved more rapidly during quiet, deep respiration, especially on the left side.

Adult

Analysis of fusion junctions of circularized chromosomes in Streptomyces griseus.

A filamentous soil bacterium, Streptomyces griseus 2247, carries a 7. 8-Mb linear chromosome. We previously showed by macrorestriction analysis that mutagenic treatments easily caused deletions at both ends of its linear chromosome and changed the chromosome to a circular form. In this study, we confirmed chromosomal circularization by cloning and sequencing the junction fragments from two deletion mutants, 404-23 and N2. The junction sequences were compared with the corresponding right and left deletion end sequences in the parent strain, 2247. No homology and a 6-bp microhomology were found between the two deletion ends of the 404-23 and N2 mutants, respectively, which indicate that the chromosomal circularization was caused by illegitimate recombination without concomitant amplification. The circularized chromosomes were stably maintained in both mutants. Therefore, the chromosomal circularization might have occurred to prevent lethal deletions, which otherwise would progress into the indispensable central regions of the chromosome.

Amino Acid Sequence

[Computerized analysis of normal associated movements of facial mimic muscles].

There have been many reports on the synkinesis of mimic muscles following facial palsy, and many efforts have been made to evaluate the degree of synkinesis. Even in normal cases, associated movements of facial muscles can been seen. Empirically, mimic muscles move in association, e.g., when the lips are opened to grin, the lateral portion of the eyebrow moves, or when the mouth is moved as in whistling, tension around the root of the nose subconsciously builds up. Our purpose was to evaluate the movements of facial mimic muscles quantitatively, to analyze them in various facial expressions, and to obtain basic data to the objective evaluation of associated movement in normal subjects. Thirty-seven normal subjects (18 males and 19 females, aged 20 to 40 years) were included in the study. A total of 24 markers were stuck to each subject's face. The threshold image process which revealed only the markers, made it possible to trace and measure the markers on the face. The shifting positions of the markers showed that they moved in accordance with the facial movement from the stationary phase to the maximum stage of movement. These positions were measured and the traces plotted on the coordinate axis. The shifting of the markers were then numerically expressed as trajectory investigation. The facial movements examined in this study consisted of eye closing, forehead wrinkling, whistling, and grinning. We found that, quantitatively, certain groups of mimic muscles might work together to make one facial expression in all the above mentioned facial movements. In normal individuals, at least 15-20% of other mimic muscle collaboration is needed in addition to main muscles to create a facial expression. This result can serve as a reference for the evaluation of abnormal associated facial movement.

Adult

[Emergency stenting for iatrogenic occlusion of internal carotid artery during percutaneous transluminal angioplasty: a case report].

The authors report the case of a 68-year-old male who underwent emergency stenting for iatrogenic occlusion of the internal carotid artery while he was receiving percutaneous transluminal angioplasty. He presented with a 1-month history of transient ischemic attacks with right-sided hemiparesis. Carotid angiography revealed a 95% eccentric stenosis at the origin of the left internal carotid artery. As the stenotic lesion was higher than the level of the third cervical vertebral body, percutaneous transluminal angioplasty was performed instead of carotid endarterectomy. During the procedure, the left internal carotid artery was dissected, then obstructed completely with rapid deterioration of his neurological condition. The Palmaz-Schatz stent was successfully deployed over the site of dissection to restore normal patency through the dissected carotid artery. Following emergency stenting, his neurological signs quickly subsided. Since then, with oral administration of antiplatelet medication, he has suffered no recurrence of cerebral ischemic events. Echo-ultrasonography 4 months after stent implantation showed good patency of the stented segment. It has been reported that angioplasty is indicated for high-risk patients or surgically inaccessible lesions in stenotic disorders of the internal carotid artery. However, there are several complications reported, including intimal dissection and restenosis. The present case emphasizes the usefulness of emergency stenting when occlusion of the internal carotid artery is complicated during percutaneous transluminal angioplasty.

Aged

Genetic analysis with calcium-induced calcium release test in Japanese malignant hyperthermia susceptible (MHS) families.

Some genetic studies have shown a linkage between malignant hyperthermia susceptibility (MHS) and chromosome 19q or the skeletal muscle ryanodine receptor (RYR1) gene. Some types of MHS seem to be caused by an abnormality of calcium-induced calcium release (CICR). We analyzed the linkage of RYR1 gene polymorphisms in Japanese MHS families and investigated the correlation between genetic evidence of RYR1 gene mutations and an accelerated rate of CICR. We studied 63 subjects who were referred to our institute for investigation of MHS. CICR rates were measured by the skinned fiber method in 23 subjects. DNA samples were collected from 63 individuals belonging to 22 unrelated families. Restriction fragment length polymorphism (RFLP) analyses on the RYR1 locus and hypervariable microsatellite analysis were performed. We found one family with a linkage between acceleration of the CICR mechanism and a group of RFLPs. In CICR tests, ten of the 11 patients who had presented with fulminant MH showed accelerated rates of CICR. Analysis for the mutation C1840T, which was performed in 63 samples, did not demonstrate an alteration in any of the patients. Although we found heterozygotes in RFLP studies, we did not recognize a specific relationship between the acceleration of CICR and the RFLPs. We suggest a linkage between the acceleration of CICR and an abnormal human RYR1 gene in MHS. These results also suggest that heterogeneity exists for MH. We conclude that genetic tests cannot replace CICR tests or caffeine-halothane contracture tests with muscle biopsy as a diagnosing test for MH in the near future.

Calcium

The intermediate form of glycine-extended adrenomedullin is the major circulating molecular form in human plasma.

Adrenomedullin (AM), a potent vasodilator peptide, is processed from its AM precursor as glycine-extended AM (AM-gly), an intermediate form of AM. Subsequently, mature AM is converted from AM-gly by enzymatic amidation. Using two kinds of radioimmunoassay which recognize the entire AM molecule (E-AM-RIA) and C-terminal amide structure (C-AM-RIA), human plasma AM immunoreactivity was chromatographically characterized. In analyses of gel filtration and reverse phase high-performance liquid chromatography, most of the AM immunoreactivity measured by E-AM-RIA was eluted at a position identical to where mature AM and AM-gly emerged and was not recognized by C-AM-RIA. These data show that immunoreactive AM measured by E-AM-RIA is not amidated. When amidated by peptidylglycine alpha-amidating enzyme, the immunoreactive AM was converted to a form that can be detected by C-AM-RIA. These results indicate that most of the total AM immunoreactivity measured by E-AM-RIA represents immunoreactivity of AM-gly and that the concentration of immunoreactive mature AM in plasma is much lower than that of AM-gly. In practice, plasma concentration of AM-gly and mature AM in healthy volunteers was 2.7 +/- 0.18 fmol/ml and 0.48 +/- 0.05 fmol/ml, respectively. Furthermore, plasma concentration of AM-gly and total AM was significantly elevated in patients with hypertension compared to normotensive control. The present data indicate that most of circulating plasma AM immunoreactivity is occupied by AM-gly, an intermediate form of AM, which may reflect the process of production of AM in tissues.

Adrenomedullin

A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes.

Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601-restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601(+) epithelial cancer patients.

Amino Acid Sequence

Lobectomy by video-assisted thoracic surgery for primary lung cancer: experiences based on provisional indications.

A retrospective study on compromised patients who underwent a lobectomy by a standard thoracotomy for stage I non-small cell lung cancer revealed them to show a poor prognosis and quality of life due to their deteriorated physical conditions. Therefore, a lobectomy by video-assisted thoracic surgery (VATS lobectomy) was performed on some of these patients according to the provisional indications based on our retrospective study which indicated that it may be beneficial. Fourteen patients underwent VATS lobectomies (VATS group). Sixteen patients who underwent lobectomy by standard thoracotomy (ST group) were compared with those of the VATS group as historical controls. Although the mean operating time for the VATS group was longer than that for the ST group, there was no significant difference. The mean amount of blood loss for the VATS group was significantly less than that for the ST group. The mean maximal postoperative serum CPK level of the VATS group was slightly less than that of the ST group. A significant difference was observed regarding the changes in performance status both before and after operation between the VATS group and the ST group. We thus considered a VATS lobectomy to be beneficial for aged patients, especially in those with restricted physical conditions.

Aged

Video-assisted thoracoscopic excision of a benign cystic mesothelioma of pleura.

We are reporting on the case of a 44-year-old woman upon which video-assisted thoracoscopic excision of a benign cystic mesothelioma of the pleura was performed. To our knowledge, this is the second report on a case of a benign cystic mesothelioma of the pleura. The cyst in our case was solitary and was easily excised. Microscopic examination revealed that the cyst was lined by a single layer of flattened and cuboidal cells. Immunohistochemical analysis revealed that the cells lining the cyst stained positively for keratin and negatively for factor VIII-related antigen. Benign cystic mesothelioma of the pleura was diagnosed based on histological findings. For seven months her condition has been monitored at our out-patient clinic with no signs of recurrence. However, continued careful observation is required because benign cystic mesothelioma often recurs locally. Local recurrence is thought to be related to incomplete resection of the tumor. Therefore, careful observations and techniques to ensure complete resection of the cyst, are important during video-assisted thoracoscopic surgery.

Adult

Thoracoscopic enucleation of a submucosal bronchogenic cyst of the esophagus: report of two cases.

Thoracoscopic enucleation of a bronchogenic cyst of the esophagus was successfully performed in two cases. The first patient was a 26-year-old female complaining of dysphagia and retrosternal discomfort. The second patient was a 56-year-old female complaining of retrosternal discomfort. A close examination revealed a cystic lesion compressing the esophagus in both cases. Three trocars were employed under general anesthesia. Thoracoscopy offering excellent visualization allowed us to perform a precise anatomical dissection between the muscle layer and the mucosa. Both patients recovered uneventfully and the symptoms disappeared postoperatively. Thoracoscopic surgery is thus considered to be beneficial for the treatment of a benign esophageal tumor because of the small chest wall entry, which might positively contribute to a favorable postoperative course.

Adult

Short-term modulation of the renin-angiotensin system does not alter plasma adrenomedullin concentration in humans.

OBJECTIVE: Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are novel hypotensive peptides produced from the same precursor. A relationship between AM and the renin-angiotensin-aldosterone (RAA) axis was reported in several studies, but the response of the above two peptides to short-term modulation of the RAA axis in humans is not yet clear. Here, we assessed the responses of AM and PAMP in patients with varying RAA system status, including renovascular hypertension (RVH) and primary aldosteronism (PA). DESIGN AND METHODS: Essential hypertension (EHT), RVH and PA patients were hospitalized and maintained on a standard diet (NaCl 10 g/day). The patients underwent a captopril (25 mg) loading test. A renin-secretion stimulating test (furosemide 1 mg/kg, i.v. +2 h of walking) and an ACTH loading test were performed for the PA patients. The plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma AM and PAMP levels were monitored before and after the loadings. RESULTS: In the basal state, significantly higher concentrations of AM and PAMP were shown in the RVH patients compared to the other groups. AM and PAMP were significantly correlated with PRA but not PAC in all patients. The AM and PAMP levels were not affected by the captopril loading with or without a hypotensive reaction. The AM and PAMP levels were increased only slightly despite the large increase in PAC induced in the PA patients by the renin-secretion stimulating and ACTH loading tests. CONCLUSION: The responses of plasma AM and PAMP to a short-term modulation of the RAA system were relatively small, despite the correlations observed between PRA and AM or PAMP.

Adrenocorticotropic Hormone

Parasympathetic activity in brain death: effect of apnea on heart rate variability.

BACKGROUND: Power spectral analysis of heart rate variability is a useful monitoring of brain-damaged patients. However, the effect of artificial ventilation is not clearly demonstrated in assessing vagal activity because the locus of its activity is originated close to the respiratory center in the brain stem. We studied heart rate variability during artificial ventilation and apnea test as part of an assessment of brain death. METHODS: Ten adult patients with severe brain damage were studied. Power spectral analysis of heart rate variability from electrocardiographic R-R intervals was integrated to compare spectral components before, during and after the apnea test. Before the test, circulatory and blood gas variables and electrocardiographic recording were obtained under controlled mechanical ventilation at a rate of 12 and 18 (/min), each for 5 min. Measurements were made for 10 min during the apnea test, and repeated thereafter as before the test. Power spectral analysis based on fast Fourier transformation was made by integrating each low- (LF: 0.04-0.15 Hz) and high- (HF: 0.15-0.40 Hz) frequency band areas. LF was assessed as sympathetic and parasympathetic nervous activity, and HF as respiratory-related parasympathetic vagal activity. The HF/LF ratio showed sympathovagal balance. RESULTS: All patients were assessed as brain dead. During apnea, PaCO2 (P<0.01) and LF (P<0.05) increased, and pH (P<0.01) and HF/LF ratio (P<0.05) decreased. Heart rate, mean arterial pressure, PaO2 and HF remained consistent throughout. CONCLUSION: It was shown that sympathovagal balance was inclined to be sympathotonic during apnea, and that there were no changes in the respiratory-related vagal activity in spite of stopping artificial ventilation.

Adolescent

Dissociation of adrenomedullin concentrations in plasma and cerebrospinal fluid in pregnant and non-pregnant women.

Adrenomedullin (AM), a potent vasodilator peptide, has been shown to act within the central nervous system to modulate fluid and electrolyte balance. AM-immunoreactive cells have been found in the anterior pituitary gland and the choroid plexus of humans. In addition, AM activity has been implicated in the regulation of maternal circulation during pregnancy. To determine the relationship between AM concentration in the cerebrospinal fluid (CSF) and plasma, we measured AM levels in CSF and plasma of pregnant (group P, n = 12) and non-pregnant (group NP, n = 10) women scheduled to undergo gynecologic or obstetric surgery. In both groups, the concentration of AM in the plasma exceeded that in the CSF. Plasma AM concentration was significantly higher in pregnant than non-pregnant women (17.3+/-5.8 vs 5.1+/-1.4 pmol/l, mean +/- S.D.; P<0.01), whereas CSF AM concentration did not differ between the two groups (1.3+/-0.9 and 0.9+/-0.4 pmol/l in groups P and NP respectively). No significant correlation was found between AM concentrations in the CSF and plasma. The present findings suggest that AM is present in the CSF and that its concentration in the CSF is regulated independently from that in the plasma.

Adrenomedullin