Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.

AFM study of the differential inhibitory effects of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) against Gram-positive and Gram-negative bacteria.

(-)-Epigallocatechin-3-gallate (EGCG), a main constituent of tea catechins, affects Gram-positive and Gram-negative bacteria differently; however, the underlying mechanisms are not clearly understood. Atomic force microscopy (AFM) was used to compare morphological alterations in Gram-positive and Gram-negative bacteria induced by EGCG and by H(2)O(2) at sub-minimum inhibitory concentrations (MICs). EGCG initially induced aggregates in the cell envelopes of Staphylococcus aureus and eventually caused cell lysis, which was not observed in cells treated with H(2)O(2). It initially induced nanoscale perforations or microscale grooves in the cell envelopes of Escherichia coli O157:H7 which eventually disappeared, similar to E. coli cells treated with H(2)O(2). An E. coli O157:H7 tpx mutant, with a defect in thioredoxin-dependent thiol peroxidase (Tpx), was more severely damaged by EGCG when compared with its wild type. Similar differing effects were observed in other Gram-positive and Gram-negative bacteria when exposed to EGCG; it caused aggregated in Streptococcus mutans, while it caused grooves in Pseudomonas aeruginosa. AFM results suggest that the major morphological changes of Gram-negative bacterial cell walls induced by EGCG depend on H(2)O(2) release. This is not the case for Gram-positive bacteria. Oxidative stress in Gram-negative bacteria induced by EGCG was confirmed by flow cytometry.

Familiarity with, knowledge of, and attitudes toward epilepsy in residents of Seoul, South Korea.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the perceptions of epilepsy in Seoul, South Korea, a country where social stigma toward epilepsy is still pronounced. METHODS: We randomly selected 1000 persons living in Seoul and performed telephone interviews regarding public awareness, knowledge, and attitudes toward epilepsy. RESULTS: Among 1000 respondents, the 92% who had read or heard about epilepsy became the subjects of the study. Word of mouth was most often referenced as a source of knowledge (78%). Forty-seven percentage believed that epilepsy is inheritable, whereas 5% thought that epilepsy is a mental illness. Marriage of their children to an epileptic person, childbearing by women with epilepsy, and employing a person with epilepsy were opposed by more than 50% of respondents. The reasons for the negative attitudes were that epilepsy was hereditary and untreatable (P < 0.05, respectively). CONCLUSIONS: Our study revealed that there still remains negative attitudes regarding the marriage, childbearing, and employment of persons with epilepsy, which may stem from misconceptions about the cause and treatability of epilepsy, possibly due in part to the influence of herbal medicine, and South Korea's ethnic homogeneity. Public health education either through media or school health education is urgently needed to improve knowledge about, and attitudes toward epilepsy.

Proton energy spectra in the nonmesonic weak decay of 12lambdaC and 28lambdaSi hypernuclei.

Numbers of protons per Gamma hypernuclear weak decay were measured as a function of proton energy above 40 MeV, explicitly identifying production of Gamma hypernuclei by the (pi+,K+) reaction. The ratios between the neutron-stimulated to proton-stimulated nonmesonic decay widths, Gamma((Lambda)n-->nn)/Gamma((Lambda)p-->np) ( = Gamma(n)/Gamma(p)) were extracted by fitting the proton energy spectra. The present result claims that the proton yields are suppressed and the Gamma(n)/Gamma(p) ratios are close to 1 both for 12LambdaC and 28LambdaSi in contradiction to theoretical expectations based on meson exchange models.

Characterization of an inducible oxidative stress response in Vitreoscilla C1.

Vitreoscilla becomes resistant to killing by hydrogen peroxide and heat shock when pretreated with nonlethal levels of hydrogen peroxide. The pretreated Vitreoscilla cells (60 microM hydrogen peroxide for 120 min) significantly increased survival of the lethal dose of 20 mM hydrogen peroxide or heat shock (22 degrees C --> 37 degrees C). This indicates the existence of an adaptive response to oxidative stress. However, cells pretreated with 60 microM hydrogen peroxide became nonresistant to a lethal dose of a menadione. This result shows that hydrogen peroxide does not induce cross-resistance to menadione in Vitreoscilla. Furthermore, Vitreoscilla treated with hydrogen peroxide, heat shock, and menadione showed a change in the protein composition, as monitored by a two-dimensional gel analysis. During adaptation to hydrogen peroxide, 12 proteins were induced. Also, 18 new proteins synthesized in response to heat shock were detected by a 2-D gel analysis. The redox-cycling agents also elicited the synthesis of 6 other proteins that were unseen with hydrogen peroxide.

Asymmetry in the nonmesonic weak decay of polarized (5)(Lambda)He hypernuclei

We have measured the asymmetric emission of protons from the nonmesonic decay of polarized (5)(Lambda)He produced by the (pi(+), K+) reaction. (5)(Lambda)He is an s-shell hypernucleus and its polarization is due to the Lambda. One expects to obtain direct information on the elementary weak Lambda-->p-->np process. The asymmetry parameter has been determined to be 0.24+/-0.22. The implication of the result is discussed.

A clinical analysis of 11 patients with chronic actinic dermatitis in Korea.

Chronic actinic dermatitis is a rare disease worldwide and also in Korea. However there has been no clinicohistologic and photobiological analysis of chronic actinic dermatitis in Korea. We examined 11 patients who were diagnosed as chronic actinic dermatitis and the results of this study were compared with previous reports. Most patients were elderly men who had erythematous papules or lichenified plaques on sun-exposed areas such as the face, neck, and dorsum of the hands with severe itching sensation. All patients had severe sensitivity to UVB and biopsied specimens showed findings of chronic eczema. Five patients had positive photopatch test materials. The patients were treated with systemic and topical steroid, cyclosporine and antihistamine.

Acantholytic dyskeratotic epidermal nevus induced by ultraviolet B radiation.

We report a case of acantholytic dyskeratotic epidermal nevus induced by repeated ultraviolet B radiation in a 16-year-old Korean girl. She had experienced pruritic skin rashes on the right side of the abdomen and flank area in a zosteriform distribution for the past 10 years. They were aggravated during the summer and spontaneously disappeared in the winter. Papules revealed acantholytic dyskeratotic cells that were diagnosed as acantholytic dyskeratotic epidermal nevus. Suberythemal and erythemal doses of UVB were irradiated to the lesional skin (right side of abdomen) and nonlesional skin (left side of abdomen) for 4 consecutive days. UVB-induced pruritic papules were observed on the lesional skin and a biopsy specimen of the papules also showed acantholytic dyskeratotic cells, which were compatible with acantholytic dyskeratotic epidermal nevus.

[Aporocotyle theragrae (Trematoda: Aporocotylidae) from the blood vessel of Theragra chalcogramma].

Two fully matured specimens were collected from the blood vessel of two fish, Theragra chalcogramma, which was bought at the Emun market of Seoul in May, 1985. The blood fluke has no pharynx and suckers. Its body surface was covered with minute spines forming fan-shaped groups, 15 microns long. The intestine was H-shaped, and the ratio of esophageal length to body length was 1:6.1-6.8. Irregular shaped testes were 109-114 in number, occupying the intercecal space from cecal bifurcation to the genital pore. The present species was identified as Aporocotyle theragrae. This is the first report of the species in Korea.

Synergism of glucose and fructose in net glycogen synthesis in perfused rat livers.

Synergism of glucose and fructose in net glycogen synthesis was studied in perfused livers from 24-h fasted rats. With either glucose or fructose alone, net glycogen deposition did not occur (p greater than 0.10 for each), whereas the addition of both together resulted in significant glycogen accumulation (net glycogen accumulation was 0.21 +/- 0.03 mumol of glucose/g of liver/min at 2 mM fructose and 30 mM glucose, p less than 0.001). To better understand this synergism, intermediary substrate levels were compared at steady state with various glucose levels in the absence and in the presence of 2 mM fructose. Independent of fructose, hepatic glucose and glucose 6-phosphate increased proportionally when glucose level in the medium was raised (r = 0.86, p less than 0.001). Unlike glucose 6-phosphate, UDP-glucose did not consistently increase with glucose (p greater than 0.10); in fact, there was a small decrease at a very high glucose level (30 mM), a result consistent with the well-established activation of glycogen synthase by glucose. With elevated glucose, the level of glucose 6-phosphate was strongly correlated with glycogen content (r = 0.71, p less than 0.01, slope = 32). Adding fructose increased the "efficiency" of glucose 6-phosphate to glycogen conversion: the effect of a given increment in glucose 6-phosphate upon glycogen accumulation was increased 2.6-fold (r = 0.73, p less than 0.01, slope = 86). A kinetic modeling approach was used to investigate the mechanisms by which fructose synergized glycogen accumulation when glucose was elevated. Based on steady-state hepatic substrate levels, net hepatic glucose output, and net glycogen synthesis rate, the model estimated the rate constants of major enzymes and individual fluxes in the glycogen metabolic pathway. Modeling analysis is consistent with the following scenario: glycogen synthase is activated by glucose, whereas glucose-6-phosphatase was inhibited. In addition, the model supports the hypothesis that fructose synergizes net glycogen accumulation due to suppression of phosphorylase. Overall, our analysis suggests that glucose enhances the metabolic flux to glycogen by inducing a build up of glucose 6-phosphate via combined effects of mass action and glucose-6-phosphatase inhibition and activating glycogen synthase and that fructose enhances glycogen accumulation by retaining glycogen via phosphorylase inhibition.