Gold serum levels in children with juvenile rheumatoid arthritis.

Serum gold levels were monitored in 66 children with juvenile rheumatoid arthritis, treated with different i.m. dosage schedules of sodium aurothiomalate (Myocrisin, Pharma Rhodia). The ages of the children varied from 1 to 15 years. Gold serum levels in children were related to the dose of Myocrisin calculated per kg of body weight or per square metre of body surface area. The results of our study indicate that in order to achieve a peak serum level at about 500--600 microgram/100 ml (25--30 micromol/l) with weekly injections, the dose of Myocrisin should be about 0.7 mg/kg, or 20 mg/m2. In order to avoid excessively high gold serum concentrations, the maximum single dose should not exceed 27 mg/m2 of body surface area.     

Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine

A long-term follow-up of approximately 50,000 children who received the Hemophilus influenzae type b capsular polysaccharide vaccine in 1974 at three months to five years of age has shown good protective efficacy in those who received the vaccine at 18 months or older. No adverse effects were observed. Analysis of paired serum samples from 514 vaccinated children showed that effective immunization with this vaccine could be performed after but not before the age of 16 to 20 months. An analysis of 956 bacteremic H. influenzae infections occurring in Finland over a period of five years showed that 94 per cent of all cases were in children under 10 years of age. Of these, 40 per cent occurred in children under 18 months, and 60 per cent in children between the ages of 1 1/2 and 9 years. These 60 per cent are potentially preventable with the capsular polysaccharide vaccine.     

Disturbed root development of permanent teeth after pediatric stem cell transplantation. Dental root development after SCT

BACKGROUND: Deficient dental root development has been reported after conventional pediatric anticancer therapy, but less information is available on stem cell transplantation (SCT) recipients. METHODS: Root-crown (R/C) ratios of fully developed permanent teeth were assessed from panoramic radiographs of 52 SCT recipients, who were treated when they were age < 10 years. Using standard deviation scores (SDSs), the authors compared the R/C ratios to the corresponding tooth and gender-specific values in a healthy population. The percentage of affected R/C ratios per individual was examined in a subgroup of 39 (SG39) patients with advanced tooth development. The effects of total body irradiation (TBI) and SCT age on the R/C ratios were studied in TBI and high-dose chemotherapy (HDC = non-TBI) groups and in 3 age groups (< or = 3.0 years, 3.1-5.0 years, > or = 5.1 years). RESULTS: Per individual, 77% of the fully developed permanent teeth were affected in SG39. At the tooth level, in 77% of the 945 teeth studied (52 patients), the R/C ratios were outside +/-2 SDSs. More teeth were affected in the TBI (85%) than in the non-TBI (55%) group (P < 0.001). The teeth of the patients who were ages 3.1-5.0 years old at SCT presented with the most severe aberrations of the R/C ratio (mean SDS = -4.4) whereas the teeth of the youngest (age < or = 3.0 years) and the oldest (age > or = 5.1 years) patients were equally affected (mean SDSs = -3.1 and -3.0, respectively). CONCLUSIONS: Disturbances of dental root growth always followed pediatric SCT. HDC alone intensely harmed root growth but TBI further increased the adverse effects that were most extensive in the patients 3.1-5.0 years at SCT. These sequelae should be taken into account during the lifelong dental follow-up to minimize the clinical consequences of dental injuries.     

Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin

Coumarin and homologous compounds are the most widely used anticoagulant drugs worldwide. They function as antagonists of vitamin K, an essential cofactor for the posttranslational gamma-glutamyl carboxylation of the so-called vitamin K-dependent proteins. As vitamin K hydroquinone is converted to vitamin K epoxide (VKO) in every carboxylation step, the epoxide has to be recycled to the reduced form by the vitamin K epoxide reductase complex (VKOR). Recently, a single coumarin-sensitive protein of the putative VKOR enzyme complex was identified in humans (vitamin K epoxide reductase complex subunit 1, VKORC1). Mutations in VKORC1 result in two different phenotypes: warfarin resistance (WR) and multiple coagulation factor deficiency type 2 (VKCFD2). Here,we report on the expression of site-directed VKORC1 mutants, addressing possible structural and functional roles of all seven cysteine residues (Cys16, Cys43, Cys51, Cys85, Cys96, Cys132, Cys135), the highly conserved residue Ser/Thr57, and Arg98, known to cause VKCFD2 in humans. Our results support the hypothesis that the C132-X-X-C135 motif in VKORC1 comprises part of the redox active site that catalyzes VKO reduction and also suggest a crucial role for the hydrophobic Thr-Tyr-Ala motif in coumarin binding. Furthermore, our results support the concept that different structural components of VKORC1 define the binding sites for vitamin K epoxide and coumarin.     

Cross-sectional tomograms obtained with four panoramic radiographic units in the assessment of implant site measurements

OBJECTIVES: The aim of this study was to evaluate the ability of four panoramic X-ray units to produce cross-sectional images and to assess the effect of interexaminer and intraexaminer variations on the results. METHODS: Cross-sectional tomograms of a human cadaver mandible were taken from two edentulous and one dentate area using four different X-ray units: OP-100 Ortho Trans (Instrumentarium Imaging Co, Tuusula, Finland), Proscan (Planmeca Co, Helsinki, Finland), Cranex-Tome and Scanora (Soredex, Orion Co, Espoo, Finland). Four different linear distances were measured from each radiograph. The mandible was then cut into 4 mm thick slices at three marked places. These slices were microradiographed and used as the gold standard for measurements made from each cross-sectional tomogram. RESULTS: Of all measurements only the thickness of the mandible in the radiographs taken with the OP-100 differed significantly (P < 0.021) from the gold standard. In the interexaminer variation, the agreement was 85% and Kappa index 0.68. In the intraexaminer reproducibility, the agreement was 76.7% and Kappa indices 0.52 and 0.50. CONCLUSIONS: The X-ray units studied were found to be similar in terms of image performance and the produced images were acceptable for dental implant placement planning. Interexaminer and intraexaminer variations can be large and the main source of error can be the interpreter him or herself.     

Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice

Cyclooxygenase (COX)-2 is expressed in hepatocellular carcinomas (HCCs) and HCC cell lines. COX-2 inhibition strongly suppresses growth of HCC cells in vitro by inducing apoptosis and reducing proliferation. Here, we evaluate the in vivo effects and mechanism of COX-2 inhibition of human HCC cell line derived xenotransplanted tumors in nude mice. Firstly, nude mice were treated with a COX-2 specific inhibitor (meloxicam) or a non-specific inhibitor (sulindac) starting 5 days prior to tumor cell injection. After 35 days mice were killed and tumors were analyzed morphologically and assayed for proliferation (Ki67), apoptosis (M30) and COX-2 expression. Secondly, mice were treated with meloxicam or sulindac after tumors had reached a diameter of at least 0.2 cm. COX-2 expression was maintained in implant tumors at levels comparable with parental cells. Selective COX-2 inhibition led to a significant reduction of tumor growth and weight. COX-2 inhibition had a significant anti-proliferative and pro-apoptotic effect on tumor cells. These results demonstrate that under experimental conditions selective COX-2 inhibition suppresses solid HCC growth in vivo and, therefore may have preventive and therapeutic potential for human HCCs.     

A novel frozen brain tissue array technique: immunohistochemical detection of neuronal paraneoplastic autoantibodies

We introduce a modification of the tissue microarray technique in which several frozen brain tissue specimens are collected to a single frozen brain array block. In the present application, we use it for the detection of neuronal paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different brain regions were collected according to a standard neuropathological autopsy protocol. Cryostat sections from each block were cut and conventionally stained. From representative areas, cylinder tissue samples from each specimen were punched and then arrayed into a recipient array block. Using the cryostat sections of this brain array, autoantibodies from seven anti-Hu-positive patient sera (confirmed by immunoblotting) were screened by immunohistochemistry. Neuronal architecture was well preserved and immunohistochemical staining was comparable to that of conventional cryostat sections. Because of the variable staining pattern in different brain areas, two anti-Hu-positive sera could be detected immunohistochemically by the one brain array. With the present array technique, it is possible to characterize the variable staining patterns of neuronal paraneoplastic autoantibodies in different locations of the human brain. The frozen brain array also allows the detection of RNA and DNA targets involved in neurological diseases.     

Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory

This study shows that bone marrow (BM) stroma expresses constitutively multiple adhesion molecules (ICAM-1, VCAM-1, MadCAM-1, P-selectin) relevant for the homing and infiltration of BM by blood derived T lymphocytes, and also the co-stimulatory molecule CD80, relevant for T cell activation. T cells were capable of homing to BM but not to thymus. Homing to BM involved the integrins LFA-1alpha and alpha4 which interact with the above constitutively expressed cell adhesion molecules (CAMs). CD3 T cells were detected together with BM resident CD11c dendritic cells (DCs), often enriched in follicle-like structures in BM parenchyma. Cognate interactions between transferred antigen specific transgenic CD4 T cells and antigen laden BM-DCs led to formation of multicellular clusters in situ in BM, to generation of lymphoblasts and to clonal T cell expansion within such clusters. The great majority of BM-CD4 T cells had a memory phenotype suggesting that the BM microenvironment facilitates maintenance of CD4 memory. These results extend and corroborate our previous findings on BM-CD8 T cell mediated immune responses. Together these findings suggest that DC-T cell interactions in BM play an important role in immune responses to blood-borne antigen and in the establishment of systemic immunity and long-term memory.     

Calcium phosphate formation and ion dissolution rates in silica gel-PDLLA composites

Sol-gel derived silicas are potential biomaterials both for tissue regeneration and drug delivery applications. In this study, both SiO(2) and calcium and phosphate-containing SiO(2) (CaPSiO(2)) are combined with poly-(DL-lactide) to form a composite. The main properties studied are the ion release rates of biologically important ions (soluble SiO(2) and Ca(2+)) and the formation of bone mineral-like calcium phosphate (CaP) on the composite surface. These properties are studied by varying the quality, content and granule size of silica gel in the composite, and porosity of the polymer. The results indicate that release rates of SiO(2) and Ca(2+) depend mostly on the formed CaP layer, but in some extent also on the granule size of silicas and polymer porosity. The formation of the bone mineral-like CaP is suggested to be induced by a thin SiO(-) layer on the composite surface. However, due to absence of active SiO(2) or CaPSiO(2) granules on the outermost surface, the suitable nanoscale dimensions do not contribute the nucleation and growth and an extra source for calcium is needed instead. The result show also that all composites with varying amount of CaPSiO(2) (10-60 wt%) formed bone mineral-like CaP on their surfaces, which provides possibilities to optimise the mechanical properties of composites.