Biomedical subjects

Manabu Minami

Publications and source records attributed to Manabu Minami.

At least 37 records · Page 2Linked to original sources

PubMed2004

Chemokines generally exhibit scavenger receptor activity through their receptor-binding domain.

Chemokines are a family of cytokines that induce directed migration of various types of leukocytes through specific interactions with a group of seven transmembrane receptors. Scavenger receptors are a heterogenous family of transmembrane molecules that commonly bind and uptake oxidized low density lipoprotein and bacteria. Here, we show that not only CXC chemokine 16 (CXCL16)/SR-PSOX, a transmembrane chemokine with scavenger receptor activity, but also 12 out of 15 chemokines examined efficiently bound scavenger receptor ligands in competition with cells expressing their specific chemokine receptors. Furthermore both the chemotactic and scavenger receptor activities of SR-PSOX/CXCL16 were similarly impaired in a series of mutants altered in the chemokine domain, indicating that SR-PSOX/CXCL16 binds scavenger receptor ligands as well as CXCR6 using highly overlapping binding motifs. Taken together, chemokines generally have scavenger receptor-like activity through their receptor-binding domain, suggesting a close evolutionary relationship between chemokines and scavenger receptors.

Amino Acid Substitution↗

PubMed2004

Heparin-binding EGF-like growth factor induces expression of lectin-like oxidized LDL receptor-1 in vascular smooth muscle cells.

Receptor-mediated endocytosis of oxidized LDL (Ox-LDL) has been implicated in lipid accumulation and vascular cell dysfunction. Lectin-like Ox-LDL receptor-1 (LOX-1) is highly inducible by proinflammatory cytokines, as well as angiotensin II and Ox-LDL in vitro. LOX-1 is expressed in macrophages and smooth muscle cells accumulated in the intima of advanced atherosclerotic plaques in vivo. Here we show that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells, induces LOX-1 expression in cultured bovine aortic smooth muscle cells. HB-EGF (1-100 ng/ml) induced LOX-1 expression, which was peaked between 8 and 16 h after HB-EGF stimulation. HB-EGF-induced expression of LOX-1 was suppressed by ZD1839, an inhibitor of EGF receptor phosphorylation. Both MEK and p38 mitogen-activated protein kinase (MAPK) inhibitors significantly blocked LOX-1 upregulation induced by HB-EGF. Phosphatidylinositol 3-kinase (PI3K) inhibitors also blocked HB-EGF-induced LOX-1 expression. HB-EGF induced phosphorylation of ERK, p38 MAPK and Akt, which were suppressed by ZD1839. Upregulated expression of LOX-1 was associated with enhanced uptake of DiI-labeled Ox-LDL in smooth muscle cells. Taken together, HB-EGF can also act as an inducer of LOX-1 expression and play an integral role in foam cell transformation, cellular dysfunction, and proliferation of smooth muscle cells in atherogenesis.

Animals↗

PubMed2004

Prolonged renal parenchymal retention of 99mTc mercaptoacetyltriglycine after nephron-sparing surgery.

OBJECTIVE: Nephron-sparing surgery is a treatment in which a part of a diseased kidney is resected and some parenchyma of the kidney is spared. Impairment of spared renal parenchyma after the surgery may cause prolonged prarenchymal retention in renal scintigraphy with Tc mercaptoacetyltriglycine (Tc-MAG3). The aim of this study was to determine whether or not parenchymal retention of Tc-MAG3 is prolonged after nephron-sparing surgery. METHODS: Twenty-two patients underwent a total of 29 Tc-MAG3 studies within 1 year after nephron-sparing surgery. In 17 patients (23 examinations) who had bilateral kidneys, the presence of diffuse prolongation of parenchymal retention was determined for the operated kidney. In all patients, the presence of regional prolongation around the surgical margin was assessed. RESULTS: Diffuse prolongation was observed in four of 10 examinations performed within 1 month after surgery and in none of 13 examinations performed later than 1 month after surgery. Regional prolongation was shown in 10 of 14 examinations performed within 1 month after surgery and in three of 15 examinations performed later than 1 month after surgery. In five patients who were studied both prior to and later than 1 month after surgery, regional prolongation was noted on the first study. On the second study, regional prolongation was improved and initial renal uptake around the surgical margin was intensified. CONCLUSIONS: Renal parenchymal retention of Tc-MAG3 is frequently prolonged in the early period after nephron-sparing surgery. Renal scintigraphy with Tc-MAG3 may aid in characterizing acute renal damage after nephron-sparing surgery.

Adolescent↗

PubMed2004

Altered biosynthesis of neuropeptide processing enzyme carboxypeptidase E after brain ischemia: molecular mechanism and implication.

In this study, using both in vivo and in vitro ischemia models, the authors investigated the impact of brain ischemia on the biosynthesis of a key neuropeptide-processing enzyme, carboxypeptidase E (CPE). The response to brain ischemia of animals that lacked an active CPE was also examined. Combined in situ hybridization and immunocytochemical analyses for CPE showed reciprocal changes of CPE mRNA and protein, respectively, in the same cortical cells in rat brains after focal cerebral ischemia. Western blot analysis revealed an accumulation of the precursor protein of CPE in the ischemic cortex in vivo and in ischemic cortical neurons in vitro. Detailed metabolic labeling experiments on ischemic cortical neurons showed that ischemic stress caused a blockade in the proteolytic processing of CPE. When mice lacking an active CPE protease were subjected to a sublethal episode of focal cerebral ischemia, abundant TUNEL-positive cells were seen in the ischemic cortex whereas only a few were seen in the cortex of wild-type animals. These findings suggest that ischemia has an adverse impact on the neuropeptide-processing system in the brain and that the lack of an active neuropeptide-processing enzyme exacerbates ischemic brain injury.

Animals↗

PubMed2004

Proteomic analysis of native metabotropic glutamate receptor 5 protein complexes reveals novel molecular constituents.

We used a proteomic approach to identify novel proteins that may regulate metabotropic glutamate receptor 5 (mGluR5) responses by direct or indirect protein interactions. This approach does not rely on the heterologous expression of proteins and offers the advantage of identifying protein interactions in a native environment. The mGluR5 protein was immunoprecipitated from rat brain lysates; co-immunoprecipitating proteins were analyzed by mass spectrometry and identified peptides were matched to protein databases to determine the correlating parent proteins. This proteomic approach revealed the interaction of mGluR5 with known regulatory proteins, as well as novel proteins that reflect previously unidentified molecular constituents of the mGluR5-signaling complex. Immunoblot analysis confirmed the interaction of high confidence proteins, such as phosphofurin acidic cluster sorting protein 1, microtubule-associated protein 2a and dynamin 1, as mGluR5-interacting proteins. These studies show that a proteomic approach can be used to identify candidate interacting proteins. This approach may be particularly useful for neurobiology applications where distinct protein interactions within a signaling complex can dramatically alter the outcome of the response to neurotransmitter release, or the disruption of normal protein interactions can lead to severe neurological and psychiatric disorders.

Algorithms↗

PubMed2004

Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain.

The adult mammalian brain retains the capacity for neurogenesis, by which new neurons may be generated to replace those lost through physiological or pathological processes. However, neurogenesis diminishes with aging, and this casts doubt on its feasibility as a therapeutic target for cell replacement therapy in stroke and neurodegenerative disorders, which disproportionately affect the aged brain. In previous studies, neurogenesis was stimulated by cerebral ischemia in young rodents, and the neurogenesis response of the aged rodent brain to physiological stimuli, such as hormonal manipulation and growth factors, was preserved. To investigate the effect of aging on ischemia-induced neurogenesis, transient (60 min) middle cerebral artery occlusion was induced in young adult (3-month) and aged (24-month) rats, who were also given bromodeoxyuridine to label newborn cells. As found in prior studies, basal neurogenesis in control, nonischemic rats was reduced with aging. Ischemia failed to stimulate neurogenesis in the dentate gyrus (DG) subgranular zone (SGZ), in contrast to results obtained previously after more prolonged (90-120 min) middle cerebral artery occlusion, but increased the number of BrdU-labeled cells in the forebrain subventricular zone (SVZ). This effect was less prominent in aged than in young adult rats, with fold-stimulation of BrdU incorporation reduced by approximately 20% and the total number of cells generated diminished by approximately 50%. BrdU-labeled cells in SVZ coexpressed neuronal lineage markers, consistent with newborn neurons. We conclude that ischemia-induced neurogenesis occurs in the aged brain, and that measures designed to augment this phenomenon might have therapeutic applications.

Aging↗

PubMed2003

Upregulation of SR-PSOX/CXCL16 and recruitment of CD8+ T cells in cardiac valves during inflammatory valvular heart disease.

OBJECTIVE: SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8+ T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease. METHODS AND RESULTS: Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8+ T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-gamma (IFN-gamma) production by CD8+ T cells. CONCLUSIONS: SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-gamma production by CD8+ T cells during inflammatory valvular heart disease.

Animals↗

PubMed2003

Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells.

Direct contacts between dendritic cells (DCs) and T cells or natural killer T (NKT) cells play important roles in primary and secondary immune responses. SR-PSOX/CXC chemokine ligand 16 (CXCL16), which is selectively expressed on DCs and macrophages, is a scavenger receptor for oxidized low-density lipoprotein and also the chemokine ligand for a G protein-coupled receptor CXC chemokine receptor 6 (CXCR6), expressed on activated T cells and NKT cells. SR-PSOX/CXCL16 is the second transmembrane-type chemokine with a chemokine domain fused to a mucin-like stalk, a structure very similar to that of fractalkine (FNK). Here, we demonstrate that SR-PSOX/CXCL16 functions as a cell adhesion molecule for cells expressing CXCR6 in the same manner that FNK functions as a cell adhesion molecule for cells expressing CX(3)C chemokine receptor 1 (CX(3)CR1) without requiring CX(3)CR1-mediated signal transduction or integrin activation. The chemokine domain of SR-PSOX/CXCL16 mediated the adhesion of CXCR6-expressing cells, which was not impaired by treatment with pertussis toxin, a Galphai protein blocker, which inhibited chemotaxis of CXCR6-expressing cells induced by SR-PSOX/CXCL16. Furthermore, the adhesion activity was up-regulated by treatment of SR-PSOX/CXCL16-expressing cells with a metalloprotease inhibitor, which increased surface expression levels of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 is a unique molecule that not only attracts T cells and NKT cells toward DCs but also supports their firm adhesion to DCs.

Animals↗

PubMed2003

Cutting edge: SR-PSOX/CXC chemokine ligand 16 mediates bacterial phagocytosis by APCs through its chemokine domain.

SR-PSOX and CXC chemokine ligand (CXCL)16, which were originally identified as a scavenger receptor and a transmembrane-type chemokine, respectively, are indicated to be identical. In this study, we demonstrate that membrane-bound SR-PSOX/CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria. Importantly, our prepared anti-SR-PSOX mAb, which suppressed chemotactic activity of SR-PSOX, significantly inhibited bacterial phagocytosis by human APCs including dendritic cells. Various scavenger receptor ligands inhibited the bacterial phagocytosis of SR-PSOX. In addition, the recognition specificity for bacteria was determined by only the chemokine domain of SR-PSOX/CXCL16. Thus, SR-PSOX/CXCL16 may play an important role in facilitating uptake of various pathogens and chemotaxis of T and NKT cells by APCs through its chemokine domain.

Animals↗

PubMed2003

Benign odontogenic tumors of the mandible and maxilla.

Benign odontogenic tumors are characterized by imaging findings of expansile growth and well-defined margins with smooth borders, and their appearance is very similar to that of odontogenic and nonodontogenic cysts. From the viewpoint of diagnostic imaging of odontogenic tumors, teeth are designed differently according to their origin from the apex or crown. Therefore, for differential diagnosis, it is necessary to select diagnostic methods that make it possible to evaluate these findings in detail. Intraoral and panoramic radiography are highly effective in examining the relationship between teeth and lesions, especially the vertical relationship. When a lesion is suspected in the mandible or maxilla on CT, MR imaging, or nuclear medicine, these procedures must be performed as supplementary imaging techniques. CT demonstrates well the degree of bone resorption, osteosclerosis, cortical bone swelling, destruction, and calcification. MR imaging is effective in differentiating between tumors and cysts, evaluating the infiltration of malignant tumors in the jawbone and surrounding soft tissue, and detecting bone marrow changes of the jaw. Differentiation between tumors and cysts must be achieved by contrast-enhanced studies. Combining plain radiography with advanced imaging techniques, including CT and MR imaging, can improve the accuracy of diagnosing odontogenic tumors.

Diagnosis, Differential↗

PubMed2003

Magnetic resonance imaging of normal and osteomyelitis in the mandible: assessment of short inversion time inversion recovery sequence.

OBJECTIVE: We sought to determine the suitable magnetic resonance imaging conditions for the short inversion time inversion recovery (STIR) sequence through the use of phantoms; to describe the signal characteristics of normal structures in the mandible; and to evaluate the usefulness of STIR images in enabling the identification of mandibular osteomyelitis on conventional T1- and T2-weighted spin-echo images. STUDY DESIGN: Suitable mandibular STIR imaging conditions were determined by varying inversion time and repetition time in each sequence. STIR magnetic resonance images of 162 healthy subjects and STIR and T1- and T2-weighted spin-echo images of 21 subjects with mandibular osteomyelitis were evaluated. RESULTS: In STIR imaging, the signal of oil was suppressed at an inversion time equaling 100 milliseconds and a repetition time equaling 1500 to 3000 milliseconds. In healthy subjects, the mandibular marrow was revealed to have high signal intensities (100%) and cortical bone had no signal intensities (100%) on STIR images. In surrounding soft tissue in these healthy subjects, the submandibular glands were shown to have high signal intensities (100%); the parotid glands had intermediate to high signal intensities (100%); the sublingual glands had high (88.9%) and intermediate to high (11.1%) signal intensities; lymph nodes had high signal intensities (100%); and the masseter muscles had intermediate signal intensities (100%) on STIR images. The lesions in bone marrow had low (75%) and low to intermediate (25%) signal intensities on T1-weighted images and high (54%), intermediate to high (29%), and intermediate (17%) signal intensities on T2-weighted images. On STIR images, the signal intensities resulted in high (75%), intermediate to high (21%), and intermediate (4%) signal intensities. CONCLUSIONS: STIR imaging is highly effective for the evaluation of bone marrow and surrounding soft tissue in terms of the detection of osteomyelitis in the mandible and the identification of inflammation spreading to soft tissue.

Adult↗

PubMed2003

Sclerosing hemangioma of the lung with cystic appearance.

A case of cystic sclerosing hemangioma of the lung is reported. A chest X-ray of a 55-year-old woman who had been suffering from a cough with sputum for several months revealed an abnormal nodular shadow. A chest CT scan revealed a solitary tumor with cystic appearance occupying S7 of the right lung and the inferior pulmonary ligament. Radiological differential diagnosis for the lesion included bronchogenic cyst, cystic Schwannoma, pulmonary necrotic carcinoid, and lung carcinoma. Right lower lobectomy was carried out and the lesion was pathologically diagnosed as sclerosing hemangioma of the lung with cystic features, expanding into the pulmonary ligament. Differential diagnosis of the cystic lesion of the lung should include cystic sclerosing hemangioma as observed in this case.

Bronchogenic Cyst↗

PubMed2003

Upregulation of mitochondrial base-excision repair capability within rat brain after brief ischemia.

The mechanism by which brief episodes of cerebral ischemia confer protection (tolerance) against subsequent prolonged ischemic challenges remains unclear, but may involve upregulation of cell injury repair capability. The mitochondrion is a key site for the regulation of cell death pathways, and damage to mitochondrial genes has been linked to a number of neurologic diseases and aging. Therefore, the authors examined the response of the DNA base excision repair (BER) pathway in rat brain mitochondria after either brief (tolerance-inducing) or prolonged (injury-producing) focal cerebral ischemia. Brief (30-minute) middle cerebral artery occlusion (MCAO) induced mild oxidative mitochondrial DNA damage and initiated a prolonged (up to 72-hour) activation above control levels of the principal enzymes of the mitochondrial BER pathway, including uracil DNA glycosylase, apurinic/apyrimidinic (AP) endonuclease, DNA polymerase-gamma, and DNA ligase. In contrast, prolonged (100-minute MCAO) ischemia induced more substantial mitochondrial oxidative DNA damage whereas elevation of BER activity was transient (approximately 1 hour), declining to less than control levels over the course of 4 to 72 hours. These data reveal the differences in BER capacity after brief or prolonged ischemia, which may contribute to the neuron's ability to resist subsequent ischemic insults.

Animals↗

PubMed2003

Computed tomography-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenoma.

We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40-50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing's or subclinical Cushing's syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5-69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adrenocortical adenomas.

Acetic Acid↗

PubMed2002

Lectin-like oxidized LDL receptor-1 (LOX-1) supports adhesion of mononuclear leukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions.

Adhesion of mononuclear leukocytes to vascular endothelial cells appears one of the initial steps in the process of atherogenesis and inflammation. We examined if LOX-1, an endothelial scavenger receptor with C-type lectin-like structure, can support adhesion of mononuclear leukocytes. Under a static condition, CHO-K1 cells stably expressing LOX-1 showed more prominent adhesion of human peripheral blood mononuclear leukocytes and THP-1 cells than untransfected CHO-K1 cells, in a temperature-independent fashion. Mononuclear leukocytes also adhered to plastic plates precoated with recombinant soluble LOX-1 extracellular domain. A neutralizing anti-LOX-1 monoclonal antibody, as well as oxidized low-density lipoprotein, significantly blocked adhesion of THP-1 cells to CHO-K1 cells overexpressing LOX-1 and bovine aortic endothelial cells. Under a flow condition, increased numbers of THP-1 cells showed rolling with reduced velocities on LOX-1-expressing CHO-K1 cells, compared with those on untransfected CHO-K1 cells. Taken together, LOX-1 can work as a cell surface receptor for mononuclear leukocytes under both static and flow conditions.

Animals↗

PubMed2002

Expression and differential processing of caspases 6 and 7 in relation to specific epileptiform EEG patterns following limbic seizures.

The caspase family of cell death proteases has been implicated in the mechanism of neuronal death following seizures. We investigated the expression and processing of caspases 6 and 7, putative executioner caspases. Brief limbic seizures were evoked by intraamygdala kainic acid to elicit unilateral death of target hippocampal CA3 neurons in the rat. Seizures rapidly induced cleavage of constitutively expressed caspase-6, followed by elevated VEIDase activity and the proteolysis of lamin A. Neuronal caspase-6 immunoreactivity was markedly upregulated within cortex and hippocampus in relation to bursts of polyspike paroxysmal discharges. In contrast, while caspase-7 expression also increased within cortical and hippocampal neuronal populations in response to the same seizure patterns, caspase-7 was not proteolytically activated. These data highlight differences in expression and activation of caspases 6 and 7 in response to identifiable seizure patterns, focusing potential therapeutic targets for neuroprotection in epilepsy.

Amygdala↗

PubMedDate not supplied

Collimator choice in cardiac SPECT with I-123-labeled tracers.

BACKGROUND: Septal penetration of high-energy photons may degrade the quality of single photon emission computed tomography (SPECT) of the heart with iodine 123-labeled tracers. We investigated the impact of collimator choice on cardiac SPECT with I-123. METHODS AND RESULTS: SPECT of a thoracic phantom containing I-123 solution was performed with a low-energy high-resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium-energy (ME) collimator, and the cavity-to-myocardium contrast, wall thickness, and defect contrast were compared among the collimators. For all indices, use of the SLEHR collimator yielded the best results. Comparison between the LEHR and ME collimators revealed that the cavity-to-myocardium contrast and contrast for large defects were better with the ME collimator, whereas wall thickness and contrast for small defects were similar. Scatter correction by the triple-energy window method improved the indices examined; however, the superiority of the SLEHR collimator was still observed after correction. CONCLUSIONS: Collimator choice substantially influences the quality of cardiac SPECT with I-123-labeled agents, and an appropriate collimator needs to be selected in consideration of septal penetration and spatial resolution.

Cardiomyopathies↗

PubMedDate not supplied

Magnetic resonance imaging findings of small round cell tumors of the ovary: a report of 5 cases with literature review.

OBJECTIVE: To study the magnetic resonance imaging characteristics of the ovarian involvement of small round cell tumors. METHODS: Magnetic resonance imaging findings were retrospectively reviewed in 5 patients seen at this institution and in 7 patients reported in the literature with ovarian small round cell tumors. Laterality, signal intensity, existence of hemorrhage, calcification, necrosis, septa, cerebroid appearance, and peripheral cysts were evaluated. RESULTS: Seven patients had bilateral disease, and the others had unilateral disease. The signal intensity was low on T1-weighted imaging (T1WI) in all cases. Signal on T2-weighted imaging (T2WI) and the degree of contrast enhancement varied. No case showed hemorrhage or calcification. Only 1 case demonstrated necrosis. Septa were observed in 3 cases, and a cerebroid appearance was observed in 5 cases. Six patients of reproductive age had multiple small cysts at the periphery of the masses. CONCLUSION: Despite the limited number of cases, peripheral small cysts in the large lobulated solid mass seemed to be a characteristic of the ovarian small round cell tumors in patients of reproductive age.

Adolescent↗