Development of a density-tapered capillary gas cell for laser wakefield acceleration.

A capillary gas cell for laser wakefield acceleration was developed with the aid of three-dimensional computational fluid dynamics simulations. The gas cell was specially designed to provide upward density tapering in the longitudinal direction, which is expected to suppress the dephasing problem in laser wakefield acceleration by keeping the accelerated electrons in the acceleration phase of the wake wave. The density-tapered capillary gas cell was fabricated by sapphire plates, and its performance characteristics were tested. The capillary gas cell was filled with a few hundred millibars of hydrogen gas, and a Ti:sapphire laser pulse with a peak power of 3.8 TW and a pulse duration of 40 fs (full width at half maximum) was sent through the capillary hole, which has a length of 7 mm and a square cross section of 350 × 350 µm2. The laser-produced hydrogen plasma in the capillary hole was then diagnosed two-dimensionally by using a transverse Mach-Zehnder interferometer. The capillary gas cell was found to provide an upward plasma density tapering in the range of 1018 cm-3-1019 cm-3, which has a potential to enhance the electron beam energy in laser wakefield acceleration experiments.

Evaluation of anti-acne properties of phloretin in vitro and in vivo.

OBJECTIVE: This study aimed to investigate the anti-acne properties of phloretin in vitro and in vivo. METHODS: Anti-microbial activity against Propionibacterium acnes (P. acnes), Propionibacterium granulosum (P. granulosum) and Staphylococcus epidermidis (S. epidermidis) were observed by the minimum inhibitory concentration (MIC) and disc diffusion methods. The anti-inflammatory effects were studied in HaCaT cells based on P. acnes-induced inflammatory mediators, including PGE2 and COX-2, examined through enzyme-linked immunosorbent assay (ELISA) and luciferase reporter gene assay. Thirty healthy subjects with whiteheads participated in the clinical study. Comedo counting, and the amount of sebum and porphyrin were measured before treatment and following 4 consecutive weeks of treatment with phloretin. RESULTS: Phloretin showed anti-microbial activities against P. acnes, P. granulosum, S. epidermidis with the MIC of 0.5, 0.5 and 0.25 mg mL(-1) , respectively. P. acnes-induced activation of the COX-2 promoter was markedly attenuated by phloretin treatment. Consistent with these results, inhibition of PGE2 production was also observed. In 1-month, placebo-controlled trials, phloretin showed clinically and statistically significant reduction of comedo counts and sebum output level. Compared to before treatment, whiteheads, blackheads, papules, sebum output level and amount of sebum and porphyrin were significantly decreased at 4 weeks in the test group. CONCLUSIONS: This study revealed that phloretin inhibits the growth of P. acnes, P. granulosum, and S. epidermidis. In addition, we demonstrated that phloretin attenuates COX-2 and PGE2 expression during the P. acnes-induced upregulation of inflammatory signalling. Clinical studies further suggested that treatment with formulations containing phloretin confers anti-acne benefits. Based on these results, we suggest that phloretin may be introduced as a possible acne-mitigating agent.

Hyaluronidase treatment of acute lymphedema in a mouse tail model.

The purpose of this study was to investigate the impact of hyaluronidase (HAase) on lymphedema using an acute mouse tail lymphedema model. Six-week-old mice served to produce acute lymphedema and were then either treated with HAase injection or used as operative controls. An additional group of unmanipulated normal mice was used for comparison. Tail volumes were measured for 23 days and histological changes examined. Western blot analysis was conducted to quantify lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, podoplanin, CD 44, and vascular endothelial growth factor receptor3 (VEGFR3) expression levels. The operative control group showed an increase in thickness of the dermis and subdermis, microlymphatic dilatation, and an increase in neutrophils. In contrast, the HAase treated group exhibited alleviation of inflammation evidenced by a decline in microlymphatic dilatation and neutrophils and an overall increase in microlymphatic vessels. Western blot analysis demonstrated that TNF-alpha and TGF-beta1 expression declined but CD44 expression increased in the HAase treated group. Levels of LYVE1, podoplanin, and VEGFR3 also increased significantly in the HAase group. Our results indicate that HAase treatment in the acute mouse tail model reduced lymphedema volume possibly through degradation of HA trafficking, which reduced inflammation and fibrosis in tissues and stimulated lymphangiogenesis.

Histone deacetylase inhibitors decrease proliferation potential and multilineage differentiation capability of human mesenchymal stem cells.

OBJECTIVES: Histone deacetylase (HDAC) is an important therapeutic target in cancer. Two of the main anticancer mechanisms of HDAC inhibitors are induction of terminal differentiation and inhibition of cell proliferation. To investigate the role of HDAC in maintenance of self-renewal and cell proliferation, we treated mesenchymal stem cells (MSCs) that originated from adipose tissue or umbilical cord blood with valproic acid (VPA) and sodium butyrate (NaBu). MATERIALS AND METHODS: Human MSCs were isolated from mammary fat tissue and cord blood. We performed MTT assay and flow cytometry-based cell cycle analysis to assess self-renewal of MSCs. In vitro differentiation assays into osteogenic, adipogenic, neurogenic and chondrogenic lineages were conducted to investigate MSC multipotency. Immunocytochemistry, Western blot and reverse transcription-polymerase chain reaction were used to interrogate molecular pathways. RESULTS: VPA and NaBu flattened the morphology of MSCs and inhibited their growth. VPA and NaBu activated the transcription of p21(CIP1/WAF1) by increasing the acetylation of histone H3 and H4 and eventually blocked the cell cycle at G2/M phase. The expression level of p16(INK4A), a cdk inhibitor that is closely related to cellular senescence, was not changed by HDAC inhibitor treatment. We performed controlled differentiation into bone, fat, cartilage and nervous tissue to elucidate the role of HDAC in the pluripotency of MSC to differentiate into functional tissues. VPA and NaBu decreased the efficiency of adipogenic, chondrogenic, and neurogenic differentiation as visualized by specific staining and reverse transcription-polymerase chain reaction. In contrast, osteogenic differentiation was elevated by HDAC inhibitor treatment. CONCLUSION: HDAC activity is essential for maintaining the self-renewal and pluripotency of MSCs.

The apolipoprotein(a) size, pentanucleotide repeat, C/T(+93) polymorphisms of apolipoprotein(a) gene, serum lipoprotein(a) concentrations and their relationship in a Korean population.

BACKGROUND: In addition to apolipoprotein(a) [apo(a)] kringle 4 variable number of tandem repeat (K4-VNTR), pentanucleotide repeat polymorphism (PNRP) and C/T(+93) polymorphism [C/T(+93)] of apo(a) gene have been suggested to be related to lipoprotein(a) [Lp(a)] concentration. We studied the distribution of these genetic polymorphisms and their relationship with Lp(a) concentrations in a Korean population. METHODS: One hundred thirty-two Korean adults were examined. Lp(a) was measured with enzyme-linked immunosorbent assay (ELISA). Apo(a) K4-VNTR was measured by high-resolution SDS-agarose gel separation and ECL Western blotting method. PNRP was measured after DNA amplification. The C/T(+93) ratio was measured by a amplification refractory mutation system. RESULTS: Lp(a) was inversely correlated with K4-VNTR (r=0.732, p<0.0001), but was associated neither with any PNRP haplotype nor with C/T(+93) by multiple regression analysis, although we found a significant decrease of Lp(a) in PNRP 9/9 individuals (p<0.01). There was a strong linkage disequilibrium between 9 haplotypes of PNRP and the T haplotype of C/T(+93). CONCLUSIONS: Inverse relationship between serum Lp(a) and K4 number of apo(a) was confirmed in normal Korean adults. PNRP 9/9 genotype appeared to have a reducing effect on Lp(a), but neither 9 haplotype heterozygotes of PNRP nor the T haplotype C/T(+93) affected Lp(a) concentrations in Koreans.

Pigmentation in Koreans: study of the differences from caucasians in age, gender and seasonal variations.

BACKGROUND: Human skin colour shows variations throughout life, and many extrinsic and intrinsic factors influence melanogenesis. Facultative pigmentation of sun-exposed skin has been suggested to reflect cumulative lifetime ultraviolet (UV) exposure in caucasians. However, pigmentary changes due to various regulatory factors may be different in dark-skinned peoples. OBJECTIVES: To observe the variations in skin colour due to ageing, gender differences and seasonal changes in Koreans with skin type IV or V. METHODS: Skin pigmentation was measured at five body sites (buttock, glabella, the V of the neck area, inner arm and dorsal forearm) using skin reflectance spectroscopy in 497 subjects (age range 0-87 years) in winter and 311 subjects (age range 0-84 years) in summer. Among these subjects, 110 were assessed in both seasons. Three independent measurements at each site were done and the average value was used as the pigmentation level. RESULTS: Constitutive pigmentation of the buttock was highest in the first decade of life. It then decreased during the second decade and this decreased level was maintained after the third decade. In contrast to caucasians, facultative pigmentation and sun exposure index did not increase with ageing. Gender differences were significant at all body sites after the first decade. Seasonal changes were apparent in dorsal forearm pigmentation. Little difference was seen in forehead pigmentation between summer and winter. CONCLUSIONS: Basal melanogenic regulation might not be different between Asians and caucasians. However, the sun exposure index may not represent lifelong cumulative UV exposure in Koreans. Age-, gender- and season-related characteristics of skin pigmentation in Koreans imply that genetically determined basal skin colour plays an important part in characterizing later responsiveness to UV radiation and sex hormones. Understanding differences between races will be helpful in studying the regulatory mechanisms of melanogenesis.

Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study.

SKI 306X is a purified extract from a mixture of three oriental herbal medicines (Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris) that have been widely used for the treatment of inflammatory diseases such as lymphadenitis and arthritis in far East Asia. A double-blind, controlled study was performed to evaluate the efficacy and safety of SKI 306X with placebo in 96 patients with classical osteoarthritis of the knee. Patients were randomized to four treatment groups: placebo, 200 mg, 400 mg and 600 mg of SKI 306X t.i.d.. Clinical efficacy and safety were evaluated for 4 weeks continuous treatment. SKI 306X demonstrated its clinical efficacy, as assessed by 100 mm visual analogue scale (VAS), Lequesne index and patients' and investigators opinion of the therapeutic effect compared with placebo (p<0.01). No significant adverse events were observed in patients treated with SKI 306X. This study demonstrated that SKI 306X, a new herbal anti-arthritic agent provided clinical efficacy in patients with osteoarthritis.

Genomic cloning and characterization of mitochondrial elongation factor Tu (EF-Tu) gene (tufM) from maize (Zea mays L.).

We have cloned and characterized a mitochondrial elongation factor Tu (EF-Tu) gene (tufM) in maize (Zea mays L.). This maize tufM gene encoded a polypeptide of 452 amino acid residues, consisting of a putative transit peptide of 55 residues and a mature EF-Tu of 397 residues. The coding region was composed of 12 exons and 11 introns that ranged from 76 to 1673bp in length. The deduced amino acid sequence showed 85.9% and 61.2% identity with Arabidopsis mitochondrial EF-Tu and Arabidopsis chloroplast EF-Tu sequence respectively. The transcription initiation site was determined to be 165bp upstream of the AUG initiation codon by primer extension analysis. Southern blot analysis revealed that the cloned EF-Tu gene was encoded by the members of small gene family in maize. Although this gene does not resemble the Arabidopsis nuclear tufA gene, which encodes the plastid EF-Tu, and does not contain sequence elements found in all cyanobacterial and plastid tufA genes, the predicted amino acid sequence includes an N-terminal extension that resembles a mitochondrial targeting sequence, and shares three unique sequence elements with mitochondrial EF-Tu's from Arabidopsis thaliana, Saccharomyces cerevisiae, and Homo sapiens. Therefore, we concluded that this gene encodes the maize mitochondrial EF-Tu.

Suppression of NF-kappaB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells.

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and development of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H(2)O(2) and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). Neutrophils generated ROS by stimulation with PMA, which was inhibited by NAC and SOD. In acinar cells, PMA-primed neutrophils increased the productions of H(2)O(2), LPO, and cytokines both time and dose dependently. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer) in acinar cells. Both NAC and SOD inhibited neutrophil-induced, oxidant-mediated alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-kappaB and decreasing cytokine production.

p53 gene mutations in Bowen's disease in Koreans: clustering in exon 5 and multiple mutations.

We analyzed the p53 protein expression and gene mutations to evaluate the role of ultraviolet radiation or other carcinogens, and possible racial differences in 17 samples from 12 Korean patients with Bowen's disease. A simple microdissection technique was used to collect the tumor cells selectively. p53 protein expression was found in eight of 17 (47%) samples. Abnormalities in polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis were observed in 16 (94%) samples. A total of 14 missense mutations were detected in eight (47%) samples; 11 were clustered in exon 5 and the remaining three were located in exon 8. UV-like mutations were seen in five of 14 (36%) mutations, but no CC to TT transitions, UV-fingerprint mutations were observed. Multiple mutations were present in two cases and double mutation in a single case. Each lesion in multiple Bowen's disease showed different mutations and was suggested to be of different clonal origins. TP53-loss of heterozygosity (LOH) was detected in four out of 15 (27%) informative samples. Clustering of mutations in exon 5 suggests the role of another carcinogen in Koreans or Asians other than the UVR. Microdissection would increase the detection rate of the p53 gene mutations and LOH not only in skin cancer but also in precancerous lesions.

Hormone replacement therapy in women with pre-existing hyperpigmented lesions.

OBJECTIVES: This study was performed to determine whether skin pigmentation is darkened after hormone replacement therapy (HRT). METHODS: The color of hyperpigmentary lesions and control sites before and after 1, 2, and 3 months of HRT was measured. RESULTS: All of the three tested sites showed no significant pigment alteration in 3 months of follow up after starting HRT (P>0.05). Age, duration of menopause, and sex hormone levels did not correlate with pigmentation level. CONCLUSIONS: Pigmentation changes after HRT are not significantly associated with the treatment. This finding suggests that low-dose estrogen replacement therapy does not induce pigmentation changes alone and that differences in individual susceptibility and end organ responsiveness or other multiple factors in addition to the sex hormone may be responsible for the development and darkening of hyperpigmentary lesions.

A case of pancytopenia secondary to low-dose pulse methotrexate therapy in a patient with rheumatoid arthritis and renal insufficiency.

Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.

A new method of stabilising the elevated laminae in open-door laminoplasty using an anchor system.

We treated 12 patients with multilevel stenosis of the cervical canal after spondylosis or ossification of the posterior longitudinal ligament by an expansive open-door laminoplasty, stabilised by using an anchor system. The preoperative sagittal diameter of the canal was 9.8 mm(+/-2.2) which was increased to 16.1 mm(+/-2.9) after surgery. The mean expansion ratio of the canal was 64% (42 to 100). The anchoring systems did not fail during the follow-up period (mean 29.5 months), and the decompression was maintained. The use of anchor systems to stabilise the posterior elements after laminoplasty is a simple and effective technique for maintaining the increased sagittal diameter of the canal.