Luc's abscess in Down syndrome - A case report.

Luc's abscess is an exceedingly rare complication of otitis media, where the middle ear infection spreads extratemporally causing a subperiosteal collection under the temporalis muscle. It is known as a benign complication of otitis media as it is thought not to involve the mastoid bone in comparison to other types of extratemporal abscesses related to otitis media. We describe a challenging case of a 19-year-old male with Down syndrome diagnosed with Luc's abscess involving the mastoid bone. A high-resolution computed tomography scan is important to determine the extent of the abscess, with or without mastoid involvement, and the presence of complications. These findings will then help to determine the surgical options. Drainage of abscesses is a simple, initial, and conservative approach but less effective compared to mastoidectomy. 'Mastoidsparing' approach should only be considered if there is complete resolution after a simple drainage and antibiotic treatment.

The atomic and electronic structures of NiO(001)∕Au(001) interfaces.

The atomic and electronic structures of NiO(001)∕Au(001) interfaces were analyzed by high-resolution medium energy ion scattering (MEIS) and photoelectron spectroscopy using synchrotron-radiation-light. The MEIS analysis clearly showed that O atoms were located above Au atoms at the interface and the inter-planar distance of NiO(001)∕Au(001) was derived to be 2.30 ± 0.05 Å, which was consistent with the calculations based on the density functional theory (DFT). We measured the valence band spectra and found metallic features for the NiO thickness up to 3 monolayer (ML). Relevant to the metallic features, electron energy loss analysis revealed that the bandgap for NiO(001)∕Au(001) reduced with decreasing the NiO thickness from 10 down to 5 ML. We also observed Au 4f lines consisting of surface, bulk, and interface components and found a significant electronic charge transfer from Au(001) to NiO(001). The present DFT calculations demonstrated the presence of an image charge beneath Ni atoms at the interface just like alkali-halide∕metal interface, which may be a key issue to explain the core level shift and band structure.

Combination treatment with alogliptin and voglibose increases active GLP-1 circulation, prevents the development of diabetes and preserves pancreatic beta-cells in prediabetic db/db mice.

AIM: Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and voglibose, an alpha-glucosidase inhibitor, have different but complementary mechanisms of action on glucagon-like peptide-1 (GLP-1) regulation and glucose-lowering effects. The present study evaluated the chronic effects of combination treatment with alogliptin and voglibose in prediabetic db/db mice. METHODS: Alogliptin (0.03%) and voglibose (0.001%) alone or in combination were administered in the diet to prediabetic db/db mice. RESULTS: After 3 weeks, voglibose treatment increased GLP-1 secretion (voglibose alone, 1.6-fold; alogliptin plus voglibose, 1.5-fold), while it decreased plasma glucose-dependent insulinotropic polypeptide (GIP) (voglibose alone, -30%; alogliptin plus voglibose, -29%). Alogliptin, voglibose and combination treatment decreased plasma DPP-4 activity by 72, 15 and additively by 80%, respectively, and increased plasma active GLP-1 levels by 4.5-, 1.8- and synergistically by 9.1-fold respectively. Combination treatment increased plasma insulin by 3.6-fold (alogliptin alone, 1.3-fold; voglibose alone, 1.8-fold), decreased plasma glucagon by 30% (alogliptin alone, 11%; voglibose alone, 8%), and prevented the development of diabetes, much more effectively than either agent alone. After 4 weeks, alogliptin, voglibose and combination treatment increased pancreatic insulin content by 1.6-, 3.4- and synergistically by 8.5-fold respectively. Furthermore, combination treatment resulted in an increased expression of insulin, pancreatic and duodenal homeobox 1 (PDX1) and glucose transporter 2 (GLUT2), and maintenance of normal beta/alpha-cell distribution in the pancreatic islet. CONCLUSIONS: Chronic treatment with alogliptin in combination with voglibose concurrently increased active GLP-1 circulation, increased insulin secretion, decreased glucagon secretion, prevented the onset of the disease, and preserved pancreatic beta-cells and islet structure in prediabetic db/db mice.

Carbon dioxide laser excision of a big epiglottic cyst.

Epiglottic cyst is usually asymptomatic and the commonest presentation is foreign body sensation in the throat. Treatment of epiglottic cysts depends on their size and on the clinical symptoms. Surgery is necessary for large ones. Various modalities of therapy include endoscopic excision, marsupialization and deroofing with or without a carbon dioxide laser. We report our experience of managing a case of a large epiglottic cyst with a carbon dioxide laser.

Topography of corticothalamic projections from the auditory cortex of the rat.

Corticothalamic projections from cortical auditory field to the medial geniculate body (MG) in the rat were systematically examined by making small injections of biocytin in cortical area Te1. All injections, confined to 400 microm in diameter, resulted in two projections terminating in the ventral (MGV) and dorsal divisions (MGD) of the MG. The projections to the MGV were evidently topographic. The rostral and caudal portions of area Te1 projected to the ventromedial and dorsolateral parts of the MGV, respectively, forming narrow bands of terminal axons that extended in the mediolateral direction in the coronal plane of the MGV. The minimum dorsoventral width of the bands ranged approximately from 100 to 300 microm. Besides, the more rostral portion of area Te1 tended to project to the more rostral side of the MGV. The projections to the MGD consistently arborized in its ventral margin made up of the deep dorsal nucleus of the MGD. A similar weak topography along the rostrocaudal direction was observed in the projections to the MGD. Large terminals were occasionally found in the MGD after the injections involving cortical layer V. The distribution of large terminals also appeared topographic along with small terminals that were the major component of labeling. Collaterals of labeled axons produced slabs of terminal field in the thalamic reticular nucleus, which also exhibited a weak topography of distribution. These results provide insights into the structural basis of corticofugal modulations related to the tonotopic organizations in the cortex and MG.

Auditory thalamic nuclei projections to the temporal cortex in the rat.

Thalamocortical projections from the auditory thalamic nuclei were examined systematically in the rat, including those from the dorsal division (MGD) of the medial geniculate body (MG), which were less clearly determined in previous studies. Injections of biocytin confined in each thalamic nucleus revealed characteristic features of projections in terms of cortical areas and layers of termination. In contrast to exclusively selective projections to cortical area Te1 from the ventral division (MGV) of the MG, diffuse and selective terminations were observed in the projections from the dorsal (MGD) and medial divisions (MGM) of the MG and the suprageniculate nucleus (SG). Diffuse termination was continuous in layer I or VI of the temporal cortex, while selective termination was in layers III and IV of discrete cortical areas. In addition to diffuse termination in the upper half of layer I of cortical areas Te1, Te2d and Te3v, the MGD and SG projections formed plexuses of axons selectively in lower layer III and layer IV of Te2d and Te3v. The SG projections targeted further the dorsal bank of the perirhinal cortex (PRh), while the MGD projections targeted in part the ventral fringe of Te1. The MGM projections terminated diffusely in layer VI of Te1 and Te3v, and selectively in lower layer III and layer IV of the rostral part of Te3v. Diffuse projections to layers I and VI from the SG and MGM extended in cortical regions over the dorsal fringe of Te1. Selective dense projections to middle cortical layers of Te2d and Te3v (especially its rostral part) indicate the existence of auditory areas, which could be involved in cross-modal interaction with visual and somatosensory system, respectively. Diffuse projections are supposed to bind information processings in these areas and the primary auditory area (Te1).

The VMAT2 gene in mice and humans: amphetamine responses, locomotion, cardiac arrhythmias, aging, and vulnerability to dopaminergic toxins.

Monoamine compartmentalization in monoaminergic neurons uses serial action of the plasma membrane and vesicular monoamine (VAMT2) transporters. We can now define the sequences of the genes encoding these transporters in mice and humans, examine influences of deletions of this gene and alteration in its expression levels in transgenic mice, and identify sequence polymorphisms in the human VMAT2 gene. Examination of VMAT2 variants can provide potential insights into roles for allelic variants at these loci in variant drug responses and in diseases linked to monoaminergic systems, including substance abuse and Parkinson's disease.

RIKEN integrated sequence analysis (RISA) system--384-format sequencing pipeline with 384 multicapillary sequencer.

The RIKEN high-throughput 384-format sequencing pipeline (RISA system) including a 384-multicapillary sequencer (the so-called RISA sequencer) was developed for the RIKEN mouse encyclopedia project. The RISA system consists of colony picking, template preparation, sequencing reaction, and the sequencing process. A novel high-throughput 384-format capillary sequencer system (RISA sequencer system) was developed for the sequencing process. This system consists of a 384-multicapillary auto sequencer (RISA sequencer), a 384-multicapillary array assembler (CAS), and a 384-multicapillary casting device. The RISA sequencer can simultaneously analyze 384 independent sequencing products. The optical system is a scanning system chosen after careful comparison with an image detection system for the simultaneous detection of the 384-capillary array. This scanning system can be used with any fluorescent-labeled sequencing reaction (chain termination reaction), including transcriptional sequencing based on RNA polymerase, which was originally developed by us, and cycle sequencing based on thermostable DNA polymerase. For long-read sequencing, 380 out of 384 sequences (99.2%) were successfully analyzed and the average read length, with more than 99% accuracy, was 654.4 bp. A single RISA sequencer can analyze 216 kb with >99% accuracy in 2.7 h (90 kb/h). For short-read sequencing to cluster the 3' end and 5' end sequencing by reading 350 bp, 384 samples can be analyzed in 1.5 h. We have also developed a RISA inoculator, RISA filtrator and densitometer, RISA plasmid preparator which can handle throughput of 40,000 samples in 17.5 h, and a high-throughput RISA thermal cycler which has four 384-well sites. The combination of these technologies allowed us to construct the RISA system consisting of 16 RISA sequencers, which can process 50,000 DNA samples per day. One haploid genome shotgun sequence of a higher organism, such as human, mouse, rat, domestic animals, and plants, can be revealed by seven RISA systems within one month.

[A comparative study on the clinical utility of cefozopran and cefpirome against complicated urinary tract infections].

Aiming at evaluating the utility of cefozopran (CZOP) against complicated urinary tract infections with the velocity of eradication of causal bacteria in early treatment and clinical efficacy by new criteria of UTIs, a comparative study was conducted using cefpirome (CPR) as the control drug. CZOP and CPR were administered by intravenous drip infusion at a dose of 1 g twice daily. The duration of treatment was for 5 days. The study method involved randomized assignment of the subjects to either group CZOP or group CPR. The results were as follows: 1. Of a total of 80 cases treated, 65 (CZOP group--32 cases, CPR group--33 cases) were evaluated for efficacy. 2. The overall clinical efficacy evaluation according to the criteria proposed by Japanese UTI Committee rated the CZOP group as 90.6% (29/32), and the CPR group as 90.9% (30/33), with no significant difference between the 2 groups. Clinical efficacy evaluated by attending physicians rated the CZOP group as 93.8% (30/32) and the CPR group as 90.9% (30/33). There was no significant difference between the 2 groups. 3. The efficacy rates to pyuria on day 2 were 26.7% and 0% for the CZOP group and the CPR group, respectively, indicating a higher efficacy rate for the former (p < 0.05). Those on after treatment were 59.4% and 54.5% for the CZOP group and the CPR group, respectively, with no significant difference between the 2 groups. 4. Regarding the bacteriological effect, the eradication rates of both groups were over 90% on day 1 and after treatment. There was no significant difference between the 2 groups. 5. Side effects occurred in 1 case (2.6%) out of 39 in the CZOP group and in 1 case (2.4%) out of 41 in the CPR group. Laboratory test value fluctuation was noted in 8 (20.5%) of 39 cases in the CZOP group and 11 (26.8%) of 41 cases in the CPR group. There was no significant difference between the 2 groups. The results indicate that CZOP achieves an early efficacy to pyuria, and is as useful as CPR against complicated urinary tract infections.

Surgical considerations regarding cochlear implantation in the congenitally malformed cochlea.

A 4-year-old girl with congenital profound deafness underwent cochlear implant surgery. Preoperative CT and MRI revealed that her inner ears had common-cavity or aplasia-type malformation. The bilateral internal auditory meatus were markedly narrowed. Audiometric examination demonstrated that only slight residual hearing remained in the low-frequency range and that a hearing aid would be of no benefit. Cochlear implantation was performed in her left ear. Because of the abnormal position of the facial nerve, the routine facial recess approach could not be performed. A canal-wall-down mastoidectomy was performed, and multichannel cochlear implant electrodes were inserted by careful drilling of the bony wall of the semicircular canal area. All 22 electrodes were completely inserted into the cavity. The patient can perceive sounds and her hearing ability is progressively improving.

Klinefelter's syndrome in the male infertility clinic.

The clinical features of patients with Klinefelter's syndrome attending a male infertility clinic have been investigated in order to consider their assisted reproduction treatment options. Over 12 years, a total of 148 patients with sterility due to azoospermia had Klinefelter's syndrome. Eight patients were shown by fluorescence in-situ hybridization (FISH) on metaphase spreads to be mosaic (46,XY/47,XXY), and 140 patients showed only 47,XXY. Small testes were observed in 95% of patients and gynaecomastia was seen in 12.4%. Half of the patients showed hypergonadotrophic hypogonadism, while others showed normogonadism (usually hypergonadotrophic). Spermatozoa were observed in semen from one patient with mosaicism and one without. Three-colour FISH revealed hyperploidy in 2.7% and 2.3% of these spermatozoa respectively. Multiple-site testicular biopsies in five recent patients were performed and yielded a specimen with round and elongated spermatids in one patient with 47,XXY karyotype. This sample was cryopreserved for future intracytoplasmic sperm injection. At follow-up, 46% of couples had chosen artificial insemination with donor sperm, and none had chosen adoption. Two patients developed testicular tumours, one a mature teratoma and the other a Leydig cell tumour. Two patients required androgen replacement therapy.

Protective role of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells.

Impairment of endothelial cells by oxidized low density lipoprotein (OxLDL) is believed to be the first step in atherogenesis. It is also believed that oxidative stress/antioxidant imbalance is involved in the cell damage by OxLDL. However, little is known about the interaction between OxLDL and antioxidants. In this study, we show that treatment of human vascular endothelial cells with OxLDL caused a gradual increase of glutathione (gamma-glutamylcysteinyl glycine, GSH) levels in 24 h. OxLDL increased the intracellular levels of reactive oxygen species (ROS) and stimulated the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for the GSH synthesis, the mitogen-activated protein kinase (MAPK) activity, and the AP-1-DNA binding activity. The luciferase activity of gamma-GCS promoter containing AP-1 site was activated by OxLDL. Collectively, OxLDL induces gamma-GCS expression mediated by AP-1 resulting in an increase of GSH levels. The MAPK activity stimulated by ROS may be involved in the activation of AP-1. The increase in GSH by OxLDL may afford cellular protection against OxLDL-induced oxidative stress.

Putative pheromone receptors related to the Ca2+-sensing receptor in Fugu.

By a combination of PCR with degenerate primers and low stringency probing, we have isolated a large family of genes related to the Ca2+-sensing receptor from the genome of Fugu rubripes. One of the genes (type I) is the Fugu homologue of the Ca2+-sensing receptor. The remaining genes can be divided into five classes (type II-VI) on the bases of gene structure. In several types, the genes occur in clusters as tandem arrays. These genes appear to be the homologues of the vomeronasal pheromone receptors recently described in rodents. The Fugu genes are expressed in the tissues of the nose, suggesting that they may have a similar physiological role.

Ectopic bone induction in porous apatite-wollastonite-containing glass ceramic combined with bone morphogenetic protein.

To accelerate the integration of ceramic implants with the surrounding bone and to search for a suitable carrier for bone morphogenetic protein (BMP), we studied ectopic bone induction in porous apatite-wollastonite-containing glass ceramic (A-W GC) combined with partially purified bovine BMP (bBMP) and recombinant Xenopus BMP-4/7 (rxBMP-4/7). Porous A-W GC rods [4 mm in diameter, 5 mm in height, 70% porosity, 200 microns mean pore size, 17.54 +/- 3.82 MPa (mean +/- SD) compressive strength] were used. An apatite coating formed on the surface of porous A-W GC that had been immersed in simulated body fluid at 36.5 degrees C for 7 days. In experiment 1, porous A-W GC rods were combined with either bBMP, collagen, or with both bBMP and collagen. The rods were implanted into subcutaneous pouches in rats and were harvested 4 weeks after implantation. Low-energy radiographic, scanning electron microscopic (SEM), and histological examinations showed ectopic bone formation and within the rods only in the porous A-W GC combined with the bBMP and collagen group. Quantitative analysis also revealed that this group alone showed a significant increase in bone formation. In experiment 2, porous A-W GC rods were combined with rxBMP and collagen, implanted into rats, and harvested as described above. SEM and histological examination showed ectopic bone formation around and within the rods. Because of its relatively high mechanical strength, ease of handling, and good osteoinductivity, porous A-W GC combined with BMP and collagen may be clinically useful in patients with large cancellous bone defects or craniomaxillofacial lesions.

Oral administration of recombinant human erythropoietin in liposomes in rats: influence of lipid composition and size of liposomes on bioavailability.

Intestinal absorption of recombinant human erythropoietin (Epo) encapsulated in liposomes (Epo/liposomes) was examined by measuring the pharmacological effects of Epo after oral administration in rats. Circulating reticulocyte counts after oral administration of Epo/liposomes showed a profile different from that after intravenous administration. Epo/liposomes 0.1 micron in diameter were absorbed more effectively than those 0.2 micron in diameter. In the 0.1 micron Epo/liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterols (SS), cholesterol (Ch), or soybean-derived sterylglucosides (SG), DPPC/SS (in molar ratio 7/2) and DPPC/Ch (7/2) showed higher efficiency in intestinal absorption than DPPC/Ch (7/4) and DPPC/SG (7/2) at a low dose by the sysmex method. Pharmacological availabilities for oral administration of Epo/liposomes were 0.74-31% and 3.3-30% as evaluated by circulating reticulocyte counts and percentage circulating reticulocytes of erythrocytes, respectively, in comparison to those for intravenous administration of the same dose.

Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein.

Human T-cell leukemia virus type I (HTLV-I) encodes a 40 kDa trans-acting protein, Tax, that regulates transcription of both the proviral and cellular genes, and can transform rat fibroblasts. To determine the functional importance of its trans-acting capacities in cell transformation, we have examined two representative pathways of transcriptional activation--HTLV-I long terminal repeat (LTR) mediated and NF-kappa B dependent--by mutational analysis of Tax. In contrast to a previous report, mutants lacking the ability to activate an NF-kappaB-dependent promoter failed to transform rat fibroblasts, whereas a mutation which abolishes the HTLV-I LTR-mediated trans-activation demonstrated a wild-type capacity for cell transformation. Stable expression of Tax competent for transformation caused enhanced DNA binding of NF-kappa B in rat fibroblasts. We also demonstrate that stable co-expression of the NFKB2 precursor, known as a member of the I kappa B proteins, with wild-type Tax blocked transformation as well as eliminated aberrant NF-kappaB activation by Tax without interference with the HTLV-I LTR-mediated trans-activation. Our results indicate that constitutive activation of NF-kappa B is essential for Tax-mediated transformation of rat fibroblasts.

Effects of orally administered liposomes with soybean-derived sterols and their glucosides on rat body weight.

The effects on Wistar rat body weight were examined after a single subcutaneous (s.c.) or oral (p.o.) administration of dipalmitoylphosphatidylcholine (DPPC) liposomes composed of soybean-derived sterols (SS) and their glucosides (SG) with or without entrapping recombinant human erythropoietin (Epo) for 1 week. Body weight increased significantly after both types of administration compared with the control groups irrespective of the existence of Epo. The neutral lipid concentration in plasma increased with the increase in body weight whereas the total contents of cholesterol and high density lipoprotein cholesterol in the plasma did not change significantly. The SS and SG suspensions following p.o. administration, however, did not alter the body weight. These findings suggest that liposomal SS and SG may be absorbed through the intestinal membrane and induce a change in the uptake of lipid, in contrast to the suspension state. SS in liposomes significantly increased body weight more than SG after p.o. administration.

Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer.

We have purified and characterized recombinant Xenopus bone morphogenetic proteins (xBMPs): homodimers of xBMP-4, 7 and heterodimers (xBMP-4/7) produced by a baculovirus expression system. Highly purified xBMPs had homogeneous NH2-termini predicted from a consensus motif, Arg-X-X-Arg, while they possessed diverse sugar chains. Implantation of xBMPs together with pure collagen carrier in rats induced new bone formation in a dose-dependent manner. The xBMP-4/7 heterodimer showed the strongest activity, with an effective dose of 1-30 micrograms, while more than 10 micrograms of xBMP-4 or 7 homodimer was required for a significant effect. Histological examination revealed that xBMP-4/7 implants showed intramembranous ossification without chondrogenesis. In primary cultures of rat bone marrow stromal cells, xBMP-4/7 induced alkaline phosphatase 3-fold more strongly than xBMP-7 and 20-fold more than xBMP-4. These results suggest that the heterodimeric form of BMP would generate the strongest signal triggering osteogenic differentiation of osteoprogenitor cells in adult tissues.

Efficient expression of a heterodimer of bone morphogenetic protein subunits using a baculovirus expression system.

Recombinant baculoviruses as expression vectors for Xenopus bone morphogenetic protein (xBMP)-2, 4 and 7 were generated. The conditioned medium of insect cells infected with the virus for xBMP-2 or 4 showed strong alkaline phosphatase-inducing activity in a mouse osteoblastic cell line, MC3T3-E1, although a large portion of the activity remained in the infected cells. In contrast, xBMP-7 was preferentially secreted into the medium, but had only weak activity. Conditioned media following simultaneous inoculation with the viruses for xBMP-7 and for xBMP-2 or 4 showed a remarkably increased level of activity. The increased activity was clearly separated from other peaks derived from single infection on a cation-exchange column and was found to arise from the disulfide-linked heterodimer consisting of xBMP-4 and 7 subunits by immunoblot analysis. The heterodimer also augmented osteocalcin production and parathyroid hormone-sensitivity more strongly than the homodimers. These results suggest that our expression system provides a convenient source of heterodimeric BMP with high osteogenic differentiation-inducing activity.

Immunotherapy of acute and recurrent herpes simplex virus type 2 infection with an adjuvant-free form of recombinant glycoprotein D-interleukin-2 fusion protein.

Previous studies demonstrated that the adjuvant-free form of a fusion protein consisting of a truncated herpes simplex virus type 1 (HSV-1) glycoprotein D and human interleukin-2 (tgD-IL-2) elicited superior protective immunity in mice. In this study, the immunotherapeutic efficacy of tgD-IL-2 against vaginal HSV-2 infection was investigated using a guinea pig model. Footpad injections of tgD-IL-2 (12.5 micrograms/dose) after the onset of primary lesions strongly suppressed recurrence in the chronic phase of infection; consequently, the number of days with lesions was reduced 65%. Continuous medication with 100 mg/kg/day acyclovir for 5 days failed to suppress recurrent infection. In a UV radiation-induced recurrence model, prophylactic tgD-IL-2 significantly suppressed both duration and severity of disease. A single injection of tgD-IL-2 plus acyclovir produced an additive effect on the suppression of the disease in the acute phase. These results suggest that tgD-IL-2 is a promising immunotherapeutic agent against HSV-2 genital infections.