bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells
Authors: Ito Mamoru , Hiramatsu Hidefumi , Kobayashi Kimio , Suzue Kazutomo , Kawahata Mariko , Hioki Kyoji , Ueyama Yoshito , Koyanagi Yoshio , Sugamura Kazuo , Tsuji Kohichiro , Heike Toshio , Nakahata Tatsutoshi 
Published: October 2002

AbstractTo establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/γcnull mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rγ (IL-2Rγ) allelic mutation (γcnull) were generated by 8 backcross matings of C57BL/6J-γcnull mice and NOD/Shi-scidmice. When human CD34+ cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the β2-microglobulin–deficient NOD/LtSz-scid (NOD/SCID/β2mnull) mice, which were as completely defective in NK cell activity as NOD/SCID/γcnull mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 × 102 CD34+ cells could grow and differentiate in this strain. These results suggest that NOD/SCID/γcnull mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/γcnull mice, cytokine production of spleen cells stimulated with Listeria monocytogenesantigens was compared among these 3 strains of mice. The interferon-γ production from dendritic cells from the NOD/SCID/γcnull mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/γcnull mice.
In the presence of bone marrow stromal cells human multiple myeloma cells become independent of the IL-6/gp130/STAT3 pathway
Authors: Chatterjee Manik , Hönemann Dirk , Lentzsch Suzanne , Bommert Kurt , Sers Christine , Herrmann Pia , Mathas Stephan , Dörken Bernd , Bargou Ralf C. 
Published: October 2002

AbstractThe interleukin 6/glycoprotein 130/signal transducer and activator of transcription 3 (IL-6/gp130/STAT3) pathway has been reported to play an important role in the pathogenesis of multiple myeloma (MM) and for survival of MM cells. However, most data concerning the role of IL-6 and IL-6–triggered signaling pathways were obtained from experiments performed with MM cell lines and without considering the bone marrow microenvironment. Thus, the precise role of IL-6 and its intracellular signaling pathways for survival of human MM cells is still unclear. Here we show that treatment of human MM cells (IL-6–dependent MM cell line INA-6 and primary MM cells) with the IL-6 receptor antagonist Sant7 or with an anti-gp130 monoclonal antibody (mAb) induced apoptosis if the cells were cultured in the absence of bone marrow stromal cells (BMSCs). In contrast, apoptosis could not be observed if the MM cells were cocultured with BMSCs. The analysis of intracellular pathways revealed that Sant7 and anti-gp130 mAb were effectively inhibiting the phosphorylation of gp130 and STAT3 in the absence and presence of BMSCs, whereas ERK1 and ERK2 (ERK1,2) phosphorylation was only slightly affected. In contrast, treatment with the farnesyl transferase inhibitor, FPT III, induced apoptosis in MM cells in the absence or presence of BMSCs and led to a complete inhibition of the Ras/mitogen-activated protein kinase pathway. These observations indicate that the IL-6/gp130/STAT3 pathway is not essential for survival of human myeloma cells if they are grown in the presence of cells from the bone marrow microenvironment. Furthermore, we provide evidence that farnesyl transferase inhibitors might be useful for the development of novel therapeutic strategies for the treatment of MM.
A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia
Authors: Spiekermann Karsten , Bagrintseva Ksenia , Schoch Claudia , Haferlach Torsten , Hiddemann Wolfgang , Schnittger Susanne 
Published: October 2002

Abstract
Activating length mutations in the juxtamembrane (JM) domain of the FLT3 gene (FLT3-LM) and mutations in the catalytic domain (FLT3D835/836) of this receptor tyrosine kinase represent the most frequent genetic alterations in acute myeloid leukemia (AML). Here, we describe a 6-bp insertion in the activation loop of FLT3 between codons 840 and 841 of FLT3 (FLT3-840GS) in 2 unrelated patients with AML. Screening for other activating mutations of FLT3, KIT, and NRASshowed no further genetic alterations in patients carrying the FLT3-840GS. In functional analyses we could show that this mutant is hyperphosphorylated on tyrosine and confers interleukin 3–independent growth to Ba/F3 cells, which can be inhibited by a specific FLT3 protein tyrosine kinase (PTK) inhibitor. Our results show for the first time that in addition to known mutations in the JM and the catalytic domain, further activating length mutations exist in theFLT3 gene.
Clonal heterogeneity in mycosis fungoides and its relationship to clinical course
Authors: Vega Francisco , Luthra Rajyalakshmi , Medeiros L. Jeffrey , Dunmire Valerie , Lee Sang-Joon , Duvic Madeleine , Jones Dan 
Published: October 2002

Abstract
Mycosis fungoides (MF) is a cutaneous T-cell lymphoma characterized by multifocal disease and protracted clinical course. The few studies that have assessed T-cell receptor (TCR) gene rearrangements (GRs) present at different anatomic sites in MF have generally reported a common clone. We used a previously validated 4-color polymerase chain reaction (PCR) assay to assess the size and V-family usage of TCR-γ GRs in 102 concurrent and/or sequential morphologically involved biopsy specimens (91 skin and 11 lymph nodes) from 39 MF patients. This assay detected TCR-γ clonal GRs in 89 samples (87%) from 36 patients (92%). In 24 patients (77%), an identical clonal GR was present in at least 2 skin samples. However, in one third of these patients, additional different clonal GRs were also noted. Four patients (13%) had clonal GRs that were distinct in different skin samples. In 3 patients (10%), no GR was detected in any sample. In a comparison of lymph node and skin samples, 8 patients had the identical clonal GRs at both sites, 2 patients had different clonal GRs, and 1 patient had no GR identified at either site. Independent of clinical stage, patients who had the same GR detected in multiple concurrent biopsy specimens at the time of diagnosis were more likely to have progressive disease than those who had different GRs (P = .04). Four-color TCR-γ PCR analysis can uncover multiple distinct clonal GRs in different samples consistent with multiclonal or oligoclonal disease in a significant proportion of MF patients. Demonstration of identical clonal GRs in multiple biopsy specimens at the time of diagnosis may provide prognostic information related to disease progression.
Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutine
Authors: Hashimoto Yoshimi , Tanaka Masami , Kishimoto Hideyuki , Shiozawa Hiroyoshi , Hasegawa Kazumasa , Matsuyama Kenji , Uchida Takahiro 
Published: October 2002

Abstract
The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1–2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method.
The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels
Authors: Fang Jia-You , Sung K C , Wang Jhi-Joung , Chu Chin-Chen , Chen Kuan-Ting 
Published: October 2002

Abstract
The in-vitro permeation of buprenorphine across skin was investigated to assess the effects of iontophoresis and electroporation on drug permeation from solutions as well as from hydrogels. Iontophoresis (0.3 mA cm−2) increased the buprenorphine permeation from solution by a factor of 14.27 as compared with passive diffusion; the application of electroporation increased the buprenorphine permeation from solutions by a factor of 8.45. The permeation experiments using cellulose membrane and stratum corneum (SC)-stripped skin as permeation barriers suggested that the enhancement with iontophoresis was primarily due to strong electrophoretic drift of buprenorphine molecules, whereas the enhancement seen with electroporation was mainly attributed to the creation of transient aqueous pores in the SC layer. Application of high-voltage pulses followed by iontophoresis resulted in a shorter permeation onset time from both solutions and hydrogels as compared with iontophoresis or electroporation alone. The charge repulsion between buprenorphine and chitosan vehicles as well as the competition effects of counter-ions for carboxymethylcellulose (CMC)-based polymers may account for the different permeation rates under electrical field. This study demonstrates the feasibility of using hydrogels for delivery of buprenorphine under the application of iontophoresis or electroporation, separately or together.
Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies
Authors: Pongjanyakul Thaned , Prakongpan Sompol , Panomsuk Suwannee , Puttipipatkhachorn Satit , Priprem Aroonsri 
Published: October 2002

Abstract
Shed king cobra skin (SKCS) and shed cobra skin (SCS) were investigated for use as barrier membranes, including some pre-hydration factors, for in-vitro nicotine permeation. Inter-specimen variations in nicotine fluxes using shed snake skin were compared with those using human epidermis. Nicotine in the form of 1% w/v aqueous buffer solution at pH 5 and transdermal patches (dose 14 mg day−1) were used. The nicotine fluxes across the shed snake skin were not significantly affected (P &gt; 0.05) by temperature and duration of hydration pre-treatment. Scanning electron micrographs of SKCS and SCS revealed a remarkable difference in surface morphology, but the nicotine fluxes using both shed skins were not significantly different (P &gt; 0.05). When compared with the results obtained using human epidermis, there were similarities in fluxes and permeation profiles of nicotine. Using nicotine solution, the nicotine permeation profiles of all membranes followed zero order kinetics. The amount of nicotine permeated provided good linearity with the square root of time over 24 h (R2 &gt; 0.98) when using nicotine patches. The nicotine fluxes using SKCS and SCS had less inter-specimen variation than those using human epidermis. The results suggest a potential use for SKCS or SCS as barrier membranes for in-vitro nicotine permeation studies.
Inhibition of proteolysis in luminal extracts from the intestine of the brushtail possum
Authors: Wen J-Y , Ledger R , Butt A G , McLeod B J , Davies N M , Tucker I G 
Published: October 2002

Abstract
The proteolytic activity of luminal extracts from five regions (duodenum, jejunum, ileum, caecum and colon) of the brushtail possum intestine towards bovine serum albumin (BSA) and human luteinizing hormone releasing hormone (LHRH) was investigated. There were no significant differences in degradation rates between fresh and previously frozen extracts from any region of the possum intestine. The inhibition of degradation of BSA by luminal extracts from two regions (jejunum and ileum) and of LHRH from four regions (jejunum, ileum, caecum and colon) was evaluated. Soybean trypsin-chymotrypsin inhibitor (SBTI), sodium deoxycholate, Carbopol 934P, bacitracin and bestatin significantly inhibited the degradation of both LHRH and BSA (P &lt; 0.05). SBTI almost totally inhibited the proteolysis of BSA and the peptidolysis of LHRH in extracts from the small intestine. This finding suggests that serine proteases such as chymotrypsin are responsible for the protein and peptide degradation in luminal extracts. It is concluded that including serine protease inhibitors in a formulation may enhance oral delivery of bioactive peptides and proteins to possums.
Ketoprofen-induced intestinal permeability changes studied in side-by-side diffusion cells
Authors: Legen Igor , Kristl Albin 
Published: October 2002

Abstract
It is known that non-steroidal anti-inflammatory drugs (NSAIDs) increase intestinal permeability. Increased intestinal permeability is believed to result from the opening of tight junctions because of NSAID-induced reduction of prostaglandin synthesis and/or energy-depletion. In this study, ketoprofen-induced changes in intestinal permeability were evaluated by measuring tissue electrical parameters, namely tissue electrical resistance (TER), short circuit current (Isc) and transepithelial potential difference (PD), and the transport of a paracellular marker, fluorescein, across rat jejunum in-vitro. Ketoprofen, added to the mucosal side of the tissue, decreased TER and increased fluorescein transport in a concentration-dependent manner. Isc values and the active transport of D-glucose were not affected at ketoprofen concentrations of less than 5 mM. Higher ketoprofen concentrations decreased Isc values and diminished active transport of D-glucose, while transport of fluorescein increased markedly. Similar effects on intestinal properties were observed when the metabolic inhibitor sodium azide was added to the incubation medium. The results of this study suggest that the increased intestinal permeability observed at lower ketoprofen concentrations (&lt; 5 mM) is most probably a consequence of reduced prostaglandin tight junction control, whereas at higher concentrations, ATP depletion caused by ketoprofen seems to be the major mechanism for increased intestinal permeability.
Retine revisited
Authors: Douglas D E 
Published: October 2002

Abstract
Retine, so named by Albert Szent-Györgyi, an inhibitor of the growth of transplanted malignant tumours in animals, is present in all mammalian tissues and in urine. Its inhibitory activity was extensively investigated by Szent-Györgyi, but its exact chemical identity was not determined. Details of the reported physical and chemical properties of retine and its ubiquitous occurrence identify it as being identical to a complex mixture of lipid 2,4-diketones of similar ubiquitous occurrence. This lipid mixture has been extensively studied, and individual members have been synthesized.
Sonolytic Control of Rate of Gold(III) Reduction and Size of Formed Gold Nanoparticles: Relation between Reduction Rates and Sizes of Formed Nanoparticles
Authors: Okitsu Kenji , Yue Akihiko , Tanabe Shuji , Matsumoto Hiroshige , Yobiko Yoshihiro , Yoo Youngeok 
Published: October 2002

Abstract
The sonochemical reduction of gold(III) [tetrachloroaurate(III)] was carried out under various irradiation conditions in an aqueous solution containing only a small amount of 1-propanol. Identical starting materials and the same initial concentrations were used in each preparation. The rates of gold(III) reduction were strongly dependent on the atmosphere, the temperature of the bulk solution, the intensity of the ultrasound, and the distance of the reaction vessel from the oscillator. For example, the rates of reduction under several atmospheres were in the order of CH4 = CO2 &lt; N2 &lt; Ne &lt; He &lt; Ar &lt; Kr, where no reduction proceeded under the CH4 and CO2 atmospheres. It was clearly found that the rates of reduction were influenced by the cavitation phenomenon. Upon irradiation, colloidal gold particles having a surface plasmon absorption were formed, although in the absence of any stabilizers for the gold particles. It was found by TEM observations that the average size of the formed gold particles changed from 30 to 120 nm by selecting the irradiation parameters. The size of the gold particles was closely correlated to the initial rate of gold(III) reduction; the higher the rate of reduction, the smaller the particles. This relationship suggested that the rate of reduction would affect the initial gold nucleation processes. In a 200 kHz standing wave system used in the present study, the strength of the generated shock waves as well as the mechanical effects could be regarded as relatively weak.
Determination of D-sorbitol in human erythrocytes by an enzymatic fluorometric method with an improved deproteinization procedure
Authors: Umeda Mamoru , Otsuka Yoko , Li Toshihiro , Matsuura Tsuneaki , Shibati Hideaki , Ota Hatsunori , Sakurabayashi Ikunosuke 
Published: October 2002

We developed an improved enzymatic assay of D-sorbitol in human erythrocytes by employing highly specific D-sorbitol dehydrogenase from Pseudomonas sp. (EC 1.1.1.14) and replacing perchloric acid (HClO 4) and potassium carbonate (K2CO3), generally used for deproteinization, with sodium hydroxide (NaOH) and zinc sulphate (ZnSO4). In this assay, erythrocytes were separated from plasma by centrifugation and washed once with physiological saline. Subsequently, the erythrocytes were lysed with distilled water and proteins precipitated with NaOH and ZnSO4. After centrifugation, the resulting colourless supernatant was mixed with a glycine buffer (pH 9·0) containing NAD+ and D-sorbitol dehydrogenase. After incubation for 30 min at 37°C, the NADH produced was measured fluorimetrically. The fluorescence intensities were corrected for sample blanks, and the values of D-sorbitol were normalized for haemoglobin content. The method had an analytical range of 1-180 µmol/L. The intra- and inter-assay precisions were < 3·3% and < 5·8%, respectively. The detection limit was 0·65 µmol/L. In terms of the linearity, precision and sensitivity, the improved method using NaOH and ZnSO4 was superior to the conventional method using HClO4 and K2CO23.
Biochemical measures in a population-based study: effect of fasting duration and time of day
Authors: Emberson JR , Whincup PH , Walker M , Thomas M , Alberti KGMM 
Published: October 2002

Background: Epidemiological studies generally aim to make simple but unbiased measurements of individuals. For this reason measurements of metabolic variables (including blood lipids, glucose and insulin) are usually carried out after a period of fasting. Few studies have examined the extent to which the use of a defined protocol for fasting in epidemiological studies abolishes the influence of fasting duration and time of day on biochemical measurements. Methods: Cross-sectional survey of British Regional Heart Study participants (4252 men aged 60-79 years), in which men without diabetes were asked to provide a blood sample after fasting for at least 6 h. Serum total, HDL and LDL cholesterol, triglyceride and insulin, and plasma glucose concentrations were measured between 08:00 h and 18:00 h. Results: Non-fasting men had lower mean LDL cholesterol and higher glucose, insulin and triglyceride levels than fasting men; these differences were more marked among diabetics. Among fasting men without diabetes, insulin and glucose levels were strongly related to time of day, falling gradually throughout the morning and remaining stable in the afternoon. Because of these relationships and the dependence of fasting duration on time of day, insulin and glucose displayed a periodic relation with fasting duration above 6 h. These associations were largely abolished by adjustment for time of day; associations with time of day were unaffected by adjustment for fasting duration. Triglyceride concentrations fell with increasing fasting duration. This relationship was also mediated through a gradual increase in triglyceride levels throughout the day. Adjustments to compensate for these variations are described. Discussion: Even after fasting, biochemical measurements may still differ in relation to fasting duration and time of day. In epidemiological studies, it is important to standardize both the period of fasting and the time of day as much as possible, and make adjustments where necessary.
Free cortisol index as a surrogate marker for serum free cortisol
Authors: Le Roux Carel W , Sivakumaran Sivajenani , Alaghband-Zadeh Jamshid , Dhillo Waljit , Kong Wing May , Wheeler Michael J 
Published: October 2002

Background: The biologically active component of a hormone is the unbound or free fraction. Changes in cortisol-binding protein could give misleading results if only total cortisol is measured for the interpretation of dynamic function tests. Methods: This study aimed to measure serum free cortisol using a steady-state gel-filtration method and then to evaluate the correlation between the serum free cortisol and the free cortisol index (FCI), defined as serum total cortisol/cortisol-binding globulin (CBG). Results: Forty-eight serum samples from healthy volunteers undergoing a short Synacthen test were analysed for total cortisol, free cortisol and CBG. The FCI correlated well with a previously established, but more complex, calculation of serum free cortisol ( R = 0·98, P <0·001) and with measured serum free cortisol ( R = 0·90, P < 0·001). Conclusion: Free cortisol index is a reliable and user-friendly measure of serum free cortisol.
Effect of anaesthetic agents on tympanometry and middle-ear effusions
Authors: Fish B. M. , Banerjee A. R. , Jennings C. R. , Frain I. , Narula A. A. 
Published: October 2002

Following informed parental consent 93 children underwent bilateral grommet insertion. Tympanometry was performed pre-operatively, and immediately prior to myringotomy. A standardized anaesthetic was used. At myringotomy the presence or absence of fluid was recorded, as well as the time since induction of the general anaesthetic.A pre-operative type B tympanogram predicted a middle-ear effusion at myringotomy in 92 per cent of patients. A pre-operative type C2 tympanogram predicted a middle-ear effusion at myringotomy in 39 per cent of patients. Sixty tympanograms (30 per cent) changed following a general anaesthetic. Fourteen type B tympanograms changed to type A and eight of these had effusions. The duration of the general anaesthetic did not influence the probability of a middle-ear effusion being present at myringotomy. A pre-operative type B tympanogram is a good predictor of middle-ear fluid. The duration of the general anaesthetic is not significant in predicting the presence of a middle-ear effusion.