Midkine inhibitors: application of a simple assay procedure to screening of inhibitory compounds.

Background: Midkine is a heparin-binding cytokine and is involved in etiology of various diseases. Thus, midkine inhibitors are expected to be helpful in treatment of many diseases.

Methods: We developed a simple assay for midkine activity based on midkine-dependent migration of osteblastic cells.

Morphological observation of the stria vascularis in midkine and pleiotrophin knockout mice.

Objectives: Midkine and Pleiotrophin are low molecular weight basic proteins with closely related structures and serve as growth/differentiation factors. They have been reported to be expressed in the cochlea during the embryonic and perinatal periods. In the present study, we focused on the roles of midkine and pleiotrophin in the stria vascularis and investigated morphological changes using mice deficient in these genes.

Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases.

Midkine is a heparin-binding cytokine or a growth factor with a molecular weight of 13 kDa. Midkine binds to oversulfated structures in heparan sulfate and chondroitin sulfate. The midkine receptor is a molecular complex containing proteoglycans.

Rationale and design of the NAGOYA HEART Study: comparison between valsartan and amlodipine regarding morbidity and mortality in patients with hypertension and glucose intolerance.

Background: Inhibitors of the renin angiotensin system are recommended as the first-line medications for diabetic hypertensive patients. However, there is less evidence supporting this recommendation especially among East Asians, a population with a unique distribution of cardiovascular disease compared to the Western population.

Methods And Results: The NAGOYA HEART Study is a prospective randomized open-label blinded-endpoint study to compare an angiotensin II receptor blocker, valsartan, and a calcium channel blocker, amlodipine, regarding their efficacies on cardiovascular morbidity and mortality in Japanese hypertensive patients with glucose intolerance.

Ca2+ extrusion via Na+-Ca2+ exchangers in rat odontoblasts.

Introduction: Intracellular Ca(2+) is essential to many signal transduction pathways, and its level is tightly regulated by the Ca(2+) extrusion system in the plasma membrane, which includes the Na(+)-Ca(2+) exchanger (NCX). Although expression of NCX1 isoforms has been demonstrated in odontoblasts, the detailed properties of NCX remain to be clarified. In this study, we investigated localization and ion-transporting/pharmacologic properties of NCX isoforms in rat odontoblasts.

[Diagnosis of HIV infection and AIDS].

The diagnosis of HIV infection is established by two steps, screening assays and confirmatory assays. The screening assays are designed to detect all infected individuals, and possess a high degree of sensitivity. The confirmatory assays are designed to identify individuals who are not infected but who have reactive screening test results, and have a high specificity.

Higher dietary intake of alpha-linolenic acid is associated with lower insulin resistance in middle-aged Japanese.

Objective: To investigate the associations between dietary intake of n-3 polyunsaturated fatty acids (plant-derived alpha-linolenic acid: ALA, and marine-derived eicosapentaenoic and docosahexaenoic acid: EPA+DHA) and insulin resistance (IR) in a lean population with high n-3 PUFA intake.

Method: We cross-sectionally studied 3383 Japanese local government workers aged 35-66 in 2002. IR was defined as the highest quartile of homeostasis model assessment, and nutrient intake was estimated from a diet history questionnaire.

Increased trabecular bone formation in mice lacking the growth factor midkine.

Midkine (Mdk) and pleiotrophin (Ptn) comprise a family of heparin-binding growth factors known primarily for their effects on neuronal cells. Since transgenic mice overexpressing Ptn have been reported to display increased bone density, we have previously analyzed Ptn-deficient mice but failed to detect any abnormality of skeletal development and remodeling. Together with the finding that Mdk expression increases in the course of primary osteoblast differentiation, we reasoned that Mdk, rather than Ptn, could play a physiologic role in bone formation.

Sodium-calcium exchangers in rat ameloblasts.

Although the central role of ameloblasts in synthesis and resorption of enamel matrix proteins during amelogenesis is well documented, the Ca(2+)-transport/extrusion mechanism remains to be fully elucidated. To clarify Ca(2+)-transport in rat ameloblasts, we investigated expression and localization of Na(+)-Ca(2+) exchanger (NCX) isoforms and the functional characteristics of their ion transporting/pharmacological properties. RT-PCR and immunohistochemical analyses revealed expression of NCX1 and NCX3 in ameloblasts, localized in the apical membrane.

[Treatment with S-1 and radiation therapy for advanced lung cancer invading chest wall].

The patient was a 63-year-old man, who had been suffering from lung cancer with left chest wall invasion and contralateral pulmonary metastases. Due to the severe pain caused by this advanced lung cancer with poor performance status (PS), oxycodone was administered for treatment. Radiotherapy was used for local tumor control and oral S-1 was given as systemic chemotherapy.

Changes in activities of daily living, physical fitness, and depressive symptoms after six-month periodic well-rounded exercise programs for older adults living in nursing homes or special nursing facilities.

A 6-month, twice weekly, well-rounded exercise program (47 sessions in total) comprised of a combination of aerobic, resistance and flexibility training was provided for institutionalized older adults aged 60 to 93. We analyzed the data of 18 older adults who could stand and had attended more than 10% of the classes (mean participation rate: 54%) to examine changes in activities of daily living (ADL), physical fitness tests and depressive moods. The mean (+/- standard deviation, range) age of the participants was 71.

A case of orthokeratinized odontogenic cyst suspected to be a radicular cyst.

This report describes a case of orthokeratinized odontogenic cyst arising in the mandibular molar region of a 39-year-old man. Under the initial clinical diagnosis of radicular cyst, root canal treatment was performed on the mandibular right second molar. The treatment that continued for six months did not achieve healing.

Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve.

Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. MK acts as a reparative neurotrophic factor in damaged peripheral nerves. A postulated role of MK in the degeneration and regeneration of sciatic nerves was explored by comparing wild-type (Mdk(+/+)) mice with MK-deficient (Mdk(-/-)) mice after freezing injury.

Heparan sulfate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2.

Transglutaminase type 2 (TG2) is both a protein cross-linking enzyme and a cell adhesion molecule with an elusive unconventional secretion pathway. In normal conditions, TG2-mediated modification of the extracellular matrix modulates cell motility, proliferation and tissue repair, but under continuous cell insult, higher expression and elevated extracellular trafficking of TG2 contribute to the pathogenesis of tissue scarring. In search of TG2 ligands that could contribute to its regulation, we characterized the affinity of TG2 for heparan sulfate (HS) and heparin, an analogue of the chains of HS proteoglycans (HSPGs).

Uric acid and left ventricular hypertrophy in Japanese men.

Background: Experimental studies have reported that allopurinol protects hypertensive rats from left ventricular hypertrophy (LVH) with negligible effects on blood pressure (BP). Uric acid (UA) was thought to induce cardiomyocyte growth and interstitial fibrosis of the heart, partly via activation of the renin-angiotensin system. In the present study, the relationship between serum UA levels and electrocardiographically-diagnosed LVH (ECG-LVH) was examined in Japanese men not taking medication for hypertension (HTN), which could confound the association.

Dopaminergic hypofunctions and prepulse inhibition deficits in mice lacking midkine.

Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in various biological phenomena such as cell migration, neurogenesis, and tissue repair. We previously demonstrated that midkine-deficient (Mdk(-/-)) mice exhibited a delayed hippocampal development with impaired working memory and increased anxiety only at the age of 4 weeks. To assess whether midkine gene could play important roles in development and maintenance of central nervous system, we investigated biochemical and behavioral parameters in dopamine and glutamate neurotransmission of Mdk(-/-) mice.

Differential expression and localization of connexins 26 and 43 in the rat gingival epithelium.

We investigated the expression and localization of connexins (CX) 26 and 43 in the rat gingival epithelium. RT-PCR analysis revealed CX26 gene expression in both the upper and lower layers of the gingival epithelium and in the total epithelial layer, whereas CX43 gene expression was limited to the lower layer and the total epithelial layer. Immunoreactivity for CX43 was observed in the membranes of adjacent cells from the basal layer to the middle of the prickle cell layer, while immunoreactivity for CX26 was observed in the granular cell layer and lower part of the squamous cell layer.

Inhibition of syndecan-1 expression and function in oral cancer cells.

Syndecan-1 has been shown to be a prognostic factor in various types of tumors, suggesting its correlation with malignancy and metastasis. In the present study, we examined the expression of syndecan-1 in oral cancer cell lines and tested whether transfection of an siRNA against human syndecan-1 affected the malignant potential of these cells. Seven different human oral cancer cell lines (HSC2, HSC3, HSC4, Ca9-22, SAS, KB and BSC-OF) were used.

Midkine is highly expressed in neuroblastoma tissues.

Purpose: Neuroblastoma (NBL) is a tumor from neural crest cells, and is the most frequent solid tumor in children. Midkine (MK) is a pleiotropin analogon, which is frequently expressed in neuronal and epithelial tumors and is a marker for a poor clinical outcome. The aims of this study were to assess MK expression in NBL and investigate the correlation with clinical outcome.

[Recurrence of severe hypophosphatemia associated with tumor neogenesis in a patient with acute lymphocytic leukemia who experienced acute renal failure due to tumor lysis syndrome].

We report a 47-year-old male patient with acute lymphocytic leukemia (ALL) who showed recurrent severe hypophosphatemia. Chemotherapy for ALL induced tumor lysis syndrome requiring hemodialysis therapy. Thereafter, severe hypophosphatemia (serum phosphorus concentration less than 0.

Glycosaminoglycan-binding cytokines as tumor markers.

A significant proportion of cytokines bind to glycosaminoglycans such as heparin. Glycosaminoglycans are involved in signaling, stabilization and/or storage of these cytokines. Typical examples of glycosaminoglycan-binding cytokines are basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), VEGF-C, hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), midkine, and pleiotrophin.

Changes in the homeostatic mechanism of dental pulp with age: expression of the core-binding factor alpha-1, dentin sialoprotein, vascular endothelial growth factor, and heat shock protein 27 messenger RNAs.

Dental pulp has various characteristics in the pulp chamber, but only a few biological evaluations about the effect of age on dental pulp tissue have been reported. The purpose of this study was to compare dental pulp from young and adult rats to characterize the homeostatic mechanism. Dental pulp cells (DPCs) were obtained from the first molar of rats, weighing 150 g each for the young group and 350 g each for the adult group.

Comparison of salivary cytokine levels in oral cancer patients and healthy subjects.

In order to find informative salivary biomarkers specific to oral cancer we examined expression of 4 kinds of cytokine in saliva. Levels of interleukins (IL-1beta, -6, -8) and osteopontin were measured by ELISA using whole saliva samples collected from 19 patients with oral cancer (9 men, 10 women; mean age, 60.9 years) and 20 healthy persons (15 men, 5 women; mean age, 32 years).

Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population.

CD4(+)CD25(+) regulatory T (Treg) cells are crucial mediators of autoimmune tolerance. The factors that regulate Treg cells, however, are largely unknown. Here, we show that deficiency in midkine (MK), a heparin-binding growth factor involved in oncogenesis, inflammation, and tissue repair, attenuated experimental autoimmune encephalomyelitis (EAE) because of an expansion of the Treg cell population in peripheral lymph nodes and decreased numbers of autoreactive T-helper type 1 (T(H)1) and T(H)17 cells.