Basic studies on the clinical applications of platelet-rich plasma.

Platelets, which contain many growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), are being used in clinical applications as platelet-rich plasma (PRP). Only a few studies, however, have been conducted on the growth factors present in PRP and on the clinical applications using the drug delivery system (DDS). For the purpose of clinical application, we first modified the PRP preparation method and assessed the amounts of growth factors contained in the human platelet concentrates.

Bernard-soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ib(beta) gene.

We report a family with Bernard-Soulier syndrome with a homozygous mutation within the GPIb(beta) gene. The proband was a 24-year-old Japanese male who has suffered from life-long bleeding tendency. The patient's sister also had severe bleeding episodes.

Different effects of various anti-GPIIb-IIIa agents on shear-induced platelet activation and expression of procoagulant activity.

Inhibitors of the platelet glycoprotein (GP)IIb-IIIa receptor (integrin alphaIIbbeta3) reduce acute thrombotic events in patients with coronary artery disease. To characterize the mechanism of action of these drugs, we evaluated the effects of different GPIIb-IIIa antagonists on shear-induced platelet aggregation, activation, and the expression of procoagulant activity. Samples of platelet-rich plasma from 16 volunteers were exposed to the shear rate of 10 800 s-1 for 6 min in an optically modified cone-plate viscometer.

[Spontaneous regression of thymoma; report of a case].

A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor.

[Routine application of trans-sternal off-pump coronary artery bypass grafting using innovative technique].

Objective: With specific apparatus and surgical techniques, we have extended the use of off-pump coronary artery bypass grafting (CABG) [OPCAB] through sternotomy approach to all of the patients with multiple coronary vessel lesions necessitating CABG. The objective of this study is to assess the safety and efficacy of our technique.

Methods: All of the consecutive 100 patients with multiple coronary vessel lesions necessitating CABG underwent trans-sternal OPCAB using our innovative technique between September 2000 and December 2002.

[Measurement of plasma von Willebrand factor cleaving protease in patients with varied thrombotic microangiopathy].

Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma of patients with TTP has been shown to contain unusually large von Willebrand factor(vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP.

Hemostatic effects of polymerized albumin particles bearing rGPIa/IIa in thrombocytopenic mice.

The recombinant fragment of the platelet membrane glycoprotein Ia/IIa (rGPIa/IIa) was conjugated to the polymerized albumin particles (polyAlb) with the average diameter of 180 nm. The intravenous administration of rGPIa/IIa-polyAlb to thrombocytopenic mice ([platelet] = 2.1+/-0.

Sex steroid hormone receptors in human thymoma.

In this study we examined the immunohistochemical localization of sex steroid receptors for estrogen alpha (ER alpha) and ER beta, progesterone-A (PR-A) and PR-B, and androgen (AR) in human thymoma (n = 132) and correlated these findings with various clinicopathological parameters. We used RT-PCR and real-time PCR to further study the expression of these receptors in 20 thymoma cases. Immunoreactivity for all sex steroid receptors was detected in the nuclei of thymoma epithelial cells.

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery.

Objective: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC).

Patients And Methods: From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients).

Results: The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance.

A rare case of a pulmonary granular cell tumor presenting as a coin lesion.

A 38-year-old man was found to show a well-defined oval-shaped homogeneous dense mass (20 x 30 mm) in the left upper lung field on chest X-ray. Left upper divisionectomy was performed under video-assisted thoracic surgery. Histology showed that the tumor cells had abundant eosinophilic granular cytoplasm, and were immunopositive for neuron-specific enolase, CD56, S-100 protein, and chromogranin.

Shear-induced von Willebrand factor-mediated platelet surface translocation of the CD40 ligand.

Background: Platelets, which can adhere to damaged vascular surfaces and release bioactive substances upon activation, may play important roles in regulating local inflammatory responses. We focused on the surface translocation of CD40 ligand (CD40L) molecules when the platelets are exposed to a high shear stress.

Method: Blood specimens were obtained from eight apparently healthy adult donors.

Functional phenotype of phosphoinositide 3-kinase p85alpha-null platelets characterized by an impaired response to GP VI stimulation.

Phosphoinositide 3-kinases (PI3Ks), a family of lipid kinases comprising 3 classes with multiple isoforms, have been shown to participate in different phases of platelet signaling. To investigate the roles that enzymes play in platelet function in vivo and determine which isoforms are important for particular signaling events, we analyzed platelet function of gene knockout mice deficient in the p85alpha regulatory subunit of heterodimeric class IA PI3K. The kinase activity of p85alpha-/- platelets was only 5% of the activity of platelets from wild-type littermates.

[Radiofrequency ablation for metastatic lung tumor].

Background: Radiofrequency ablation (RFA) is a thermal ablation technique which results in coagulative necrosis. Several preliminary studies have evaluated the efficacy of RFA for liver tumor and benign prostate disease, but few studies for lung tumor. We experienced RFA for a metastatic lung tumor and it was effective.

Granulocyte transfusion as a treatment for enterococcal meningoencephalitis after allogeneic bone marrow transplantation from an unrelated donor.

Bacterial meningoencephalitis occurring in the pre-engraftment period after bone marrow transplantation (BMT) is a rare complication, and the feasibility of granulocyte transfusion (GTX) in such cases remains to be elucidated. A 37-year-old man developed enterococcal meningoencephalitis during a severely granulocytopenic pre-engraftment period after BMT. Despite therapy with appropriate antibiotics, cultures of blood and cerebro-spinal fluid (CSF) continued to grow Enterococcus faecalis, and he developed rapid mental deterioration and seizure.

Evaluation of the combined effect of pranlukast during high-dose steroid inhalation.

In 40 patients with moderate to severe persistent adult asthma who had been requiring more than 1200 micrograms/day of beclomethasone dipropionate (CAS 5534-09-8, BDP) inhalation, the present study evaluated the combined effects of pranlukast (CAS 103177-37-3, Onon) during highdose steroid inhalation (20 in the pranlukast group and 20 in the control group). In the pranlukast group, 450 mg/day of pranlukast was administered. The course of these patients was monitored for 6 weeks during which the dose of BDP was decreased to 1/2 of the initial dose 2 weeks later and to 1/4 of the initial dose additional 4 weeks later.

Retinoid receptors in the developing human lung.

Nuclear receptors and their ligands are known to play very important roles in lung development. Among these receptors, retinoid receptors, members of the steroid/thyroid hormone receptor superfamily, are classified into retinoic acid receptor (RAR) isoforms alpha, beta, and gamma and retinoid X receptor (RXR) isoforms alpha, beta, and gamma. In addition, isoforms I and II of the orphan receptor chicken ovalbumin upstream promoter-transcription factor (COUP-TF) have been shown to negatively regulate the activation of retinoid receptors.

Computed tomographic image comparison between mediastinal and lung windows provides possible prognostic information in patients with small peripheral lung adenocarcinoma.

Objectives: The purpose of this study was to determine whether the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor of small peripheral lung adenocarcinoma.

Methods: We studied the computed tomographic images of 143 patients with primary peripheral lung adenocarcinoma of 30 mm or less in maximum diameter. Two groups were categorized according to the tumor's ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image (tumor's area in the mediastinal computed tomographic image/tumor's area in lung computed tomographic image x 100%), both faint density-type (<50%) and solid-type images (>/=50%).

[Assessment of mode of recurrence after surgical treatment for thymic carcinoma].

In order to establish an appropriate treatment for thymic carcinoma, clinical courses of 15 patients with type C thymoma of WHO classification were reviewed. Five-years survival rate in all patients was 37.6%.

Diastereoselectivity controlled by electrostatic repulsion between the negative charge on a trifluoromethyl group and that on aromatic rings.

Intramolecular electrostatic repulsions between the local negative charge on a trifluoromethyl group and that on the ortho position of an aryl moiety of a nucleophile was found to be a controlling factor of the diastereoselectivity in a cyclopropanation reaction, in which the electrostatic repulsion was evaluated quantitatively.

Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion through platelet-dependent mechanisms.

Background: Although precise mechanisms remain to be determined, recent studies show that heme oxygenase-1 (HO-1), providing endogenous carbon monoxide (CO) and bilirubin, serves as an antiinflammatory enzyme. This study aimed to clarify roles of CO in regulation of microvascular adhesion of platelets and leukocytes in endotoxemia.

Methods: Rats pretreated with or without hemin were anesthetized with pentobarbital and received continuous infusion of endotoxin.

Rolling properties of rGPIbalpha-conjugated phospholipid vesicles with different membrane flexibilities on vWf surface under flow conditions.

The recombinant fragment of the platelet membrane glycoprotein, rGPIbalpha, was conjugated to phospholipid vesicles with the average diameter of ca. 1 microm using N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). We used five kinds of rGPIbalpha-vesicles with different fluorescent anisotropies of 1,6-diphenyl-1,3,5-hexatriene (DPH) to study the rolling properties of the vesicles on the von Willebrand factor (vWf)-immobilized surface.

Fluvastatin prevents development of arterial stiffness in haemodialysis patients with type 2 diabetes mellitus.

Background: Arterial stiffness assessed by pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality in diabetic patients with end-stage renal disease. We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on arterial PWV values in this population.

Methods: Twenty-two patients with normal serum lipid levels received fluvastatin (20 mg/day p.

Reconstitution of adhesive properties of human platelets in liposomes carrying both recombinant glycoproteins Ia/IIa and Ib alpha under flow conditions: specific synergy of receptor-ligand interactions.

Liposomes carrying both recombinant glycoprotein Ia/IIa (rGPIa/IIa) and Ib alpha (rGPIb alpha) (rGPIa/IIa-Ib alpha-liposomes) instantaneously and irreversibly adhered to the collagen surface in the presence of soluble von Willebrand factor (VWF) at high shear rates, in marked contrast with translocation of liposomes carrying rGPIb alpha alone on the VWF surface. In the absence of soluble VWF, the adhesion of rGPIa/IIa-Ib alpha-liposomes to the collagen surface decreased with increasing shear rates, similar to liposomes carrying rGPIa/IIa alone. While adhesion of liposomes with exofacial rGPIa/IIa and rGPIb alpha densities of 2.

A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibalpha.

Platelet glycoprotein (GP) Ib/IX/V complex mediates high-shear dependent platelet activation through an interaction with the von Willebrand factor (vWF). All four subunits of the complex have a structural motif, the leucine-rich repeat (LRR) sequence, with leucines in conserved positions. Here we report a new polymorphism, Leu/Phe at residue 70 of GPIbalpha, which disrupts the consensus sequence of the LRR in the vWF binding domain.