Mucopolysaccharidosis type II (Hunter disease): Identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients

Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT-PCR method. Transient expression in the enzyme-deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45–56 kD) were not detected by Western blot analysis. Further more, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA. © 1995 Wiley-Liss, Inc.     

Synthesis and properties of polymers containing 4- or 4′-chalconecarbonyl groups in side chains

Photocrosslinkable polymers containing chalconecarbonyl units were prepared. 2-Methacryloyloxyethyl 4-chalconecarboxylate ( 1 ) and 2-methacryloyloxyethyl 4′chalconecarboxylate ( 2 ) were synthesized and polymerized by a radical initiator. 1 was copolymerized with methyl methacrylate. The properties of the resulting polymers as photosensitive resins are described.     

The combination of IFN-alpha2 and IFN-alpha8 exhibits synergistic antiproliferative activity on renal cell carcinoma (RCC) cell lines through increased binding affinity for IFNAR-2.

Although there are at least 13 interferon-alpha (IFN-alpha) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-alpha interactions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-alpha2 and IFN-alpha8 using six renal cell carcinoma (RCC) cell lines. Although IFN-alpha8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-alpha2 and IFN-alpha8. To analyze the interactions between IFN-alpha2 and IFN-alpha8, the receptor-binding kinetics of different combinations of IFN-alpha2 and IFN- alpha8 to the IFN-alpha receptors, IFNAR-1 or IFNAR-2, were measured using a surface plasmon resonance-based biosensor. Unexpectedly, the receptor binding kinetics to IFNAR-2 but not to IFNAR-1 were mutually related to antiproliferative activity and increase in the binding speed (K(a)) for IFNAR-2. Moreover, we observed the increased fluorescence intensity (FI) of biotin-labeled IFN-alpha8 to IFNAR-2 by receptor binding inhibition assay with unlabeled IFN-alpha2 but not the other combinations. These findings indicate that the binding manner of IFN-alpha8 for IFNAR-2 is different from that of IFN-alpha2, suggesting that binding of IFN-alpha8 rather than binding of IFN-alpha2 to IFNAR-2 leads to activation and subsequent antiproliferative activity despite the same antiviral activity in RCC.     

Balanced complex rearrangement involving chromosomes 8, 9, and 12 in a normal mother,derivative chromosome 9 with recombinant chromosome 12 in her daughter with minor anomalies

We report on a 19-month-old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,?9,?12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low-set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be balanced. © 1993 Wiley-Liss, Inc.     

DETECTION OF HBsAg IN THE PANCREAS

Hepatitis B surface antigen (HBsAg) has been reported to be present in other organs than the liver.^3,9 So far as our knowledge is concerned, however, any report of cases dealing with pancreatic diseases induced by hepatitis B virus (HBV) has not been described in the English and Japanese literature. We report an autopsy case with a pancreatic lesion characterized by damage of both exocrine and endocrine epithelial cells with inflammatory response, which were immunohistochemically found to be positive for HBsAg, and electron-microscopically to possess core-like particles In the nucleus and cytoplasm.     

Vinyl polymerization. 294. Decomposition of tetramethyltetrazene in the presence of p-substituted benzyl chlorides

A study was made of the polymerization of acrylonitrile in dimethylformamide (DMF) initiated by the binary systems of tetramethyltetrazene (TMT) and p-substituted benzyl chlorides. The polymerization rate increased linearly with the σ-constants of substituents as electron-releasing groups were introduced to the phenyl ring of benzyl chloride. In order to elucidate the initiation mechanism of the polymerization, a kinetic investigation was also undertaken of the decomposition of TMT in the presence of p-substituted benzyl chlorides in DMF. The decomposition rate was first-order in TMT and first-order in p-substituents benzyl chloride. The decomposition rate also increased with the σ constants of substituents as electron-releasing groups were introduced. On the basis of the results, the initiation mechanism for the polymerization was discussed.     

Effects of drug adherence on patient outcomes to early treatment for Japanese cedar pollinosis]

Drug adherence is one of the important aspects in caring for patients with allergic rhinitis. To improve clinical efficacy of early treatment for Japanese cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients' outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was assessed using patients' ratings of nasal and ocular symptoms and overall assessment in their condition compared with previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to February. Five hundred one patients taking early treatment were enrolled. Compared to low adherence patients, those who reported higher level of adherence significantly improved overall health condition, and achieved better symptom relief of rhinorrhea and nasal congestion. In multiple logistic regression analysis, the following factors were independent risk factors for low adherence: student (p=0.002), using OTC medications (p=0.006), and short-duration of medication (p=0.001). Low costs were also risk factor for low adherence. We conclude that taking medications for JCP for 22-28 days is the best way to enhance patients' outcomes.     

Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique

Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human -globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5° C for 20 min and at 43.0° C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5° C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 g/egg) alone, mitomycin C (10 g/egg) alone, carboplatin (10 g/egg) alone, and cisplatin (10 g/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model.     

Effects of sodium and temperature on tension in isolated canine coronary artery

The effects of sodium and temperature on tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the strength of tension was inversely related to the Na concentration. At 37°C, the tension was significantly increased at 70mEq·l ^–1 Na and below. The tension was gradually suppressed by lowering of the temperature from 37°C to 10°C. At 10°C, tension did not developed significantly at Na concentrations between 127mEq·l ^–1 and 12mEq·l ^–1.It was concluded that the decrease in Na concentrations increased the tension of the canine coronary artery and the lowering of temperature supressed the tension inducted by the decrease in Na concentrations.(Yoshida K, Fujii Y, Ina H, et al.: Effects of sodium and temperature on tension in isolated canine coronary artery. J Anesth 5: 56–59, 1991)