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PubMed1979

A Y chromosome associated factor in strain BXSB producing accelerated autoimmunity and lymphoproliferation.

Strain BXSB/Mp mice develop a spontaneous lupus-like syndrome which is strikingly accelerated in males. The accelerated autoimmune disease occurs in male F1 hybrids with strains NZB/BINJ, SJL/J, and C57BL/6J when the male parent is BXSB but not in the reciprocal hybrid male nor in females. The pattern is similar in F2 hybrids with strains NZB and SJL. The accelerated disease in males occurs only when the Y chromosome is derived from recombinant inbred strain BXSB and ultimately from strain SB/Le.

Animals↗

PubMed2006

Increased enantioselectivity and remarkable acceleration of lipase-catalyzed transesterification by using an imidazolium PEG-alkyl sulfate ionic liquid.

Several types of imidazolium salt ionic liquids were prepared derived from poly(oxyethylene)alkyl sulfate and used as an additive or coating material for lipase-catalyzed transesterification in an organic solvent. A remarkably increased enantioselectivity was obtained when the salt was added at 3-10 mol % versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed transesterification of 1-phenylethanol by using vinyl acetate in diisopropyl ether or a hexane solvent system. In particular, a remarkable acceleration was accomplished by the ionic liquid coating with lipase PS in an iPr(2)O solvent system while maintaining excellent enantioselectivity; it reached approximately 500- to 1000-fold acceleration for some substrates with excellent enantioselectivity. A similar acceleration was also observed for IL 1-coated Candida rugosa lipase. MALDI-TOF mass spectrometry experiments of the ionic-liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.

Candida↗

PubMed2005

A pilot study of high-dose intraarterial cisplatin chemotherapy with concomitant accelerated radiotherapy for patients with previously untreated T4 and selected patients with T3N0-N3M0 squamous cell carcinoma of the upper aerodigestive tract.

BACKGROUND: This Phase I clinical trial was developed to assess the feasibility of combining high-dose intraarterial cisplatin chemotherapy with concurrent, concomitant boost accelerated radiation therapy for patients with previously untreated T4 and select patients with T3N0-N3M0 squamous cell carcinoma of the upper aerodigestive tract. METHODS: Between July 1999, and February 2002, 19 patients were treated with 3 or 4 weekly cycles of intraarterial Cisplatin chemotherapy (150 mg/m(2)) with concurrent, concomitant boost accelerated radiation therapy (72 grays in 42 fractions over 6 weeks). RESULTS: Two patient deaths occurred among the first 15 patients enrolled. Both patients presented with febrile neutropenia, and both died of complications related to infection. The number of cycles of intraarterial cisplatin was reduced from four cycles to three cycles, and an additional four patients were treated. The fourth patient treated on the modified protocol developed febrile neutropenia, sepsis, and a thromboembolic event, which resulted in lower extremity amputations. The maximum acute toxicity experienced was Grade 2 in 6 patients, Grade 3 in 5 patients, Grade 4 in 6 patients, and Grade 5 in 2 patients. With a median follow-up of 21 months (range, 6.2-34.6 months), the overall survival at 1 year was 89.5% (95% confidence interval [95%CI], 76.7-100%). At 1 year, 92.9% of the patients were free from disease progression (95%CI, 80.3-100%). CONCLUSIONS: The results of this study suggest that concurrent intraarterial cisplatin chemotherapy at a dose of 150 mg/m(2) with concomitant boost accelerated radiation therapy is not feasible.

Adult↗

PubMed2006

Pilot study of lonafarnib, a farnesyl transferase inhibitor, in patients with chronic myeloid leukemia in the chronic or accelerated phase that is resistant or refractory to imatinib therapy.

BACKGROUND: Lonafarnib (SCH66336) is a nonpeptidomimetic farnesyl transferase inhibitor that has demonstrated significant preclinical activity against chronic myelogenous leukemia (CML) cells and in CML animal models. METHODS: In the current study, the efficacy of lonafarnib was investigated in patients with CML in the chronic or accelerated phase that was resistant or intolerant to imatinib. Thirteen patients with CML in the chronic (n = 6 patients) or accelerated (n = 7 patients) phase were treated with lonafarnib at a dose of 200 mg orally twice daily. Ten patients had failed therapy with imatinib and 3 patients were intolerant to imatinib. The median age of the patients was 62 years (range, 38-80 yrs) and the median time from the diagnosis of CML to therapy with lonafarnib was 5 years (range, 0.3-13 yrs). In addition to imatinib mesylate, all patients had received prior therapy with interferon-alpha and seven patients had received other treatments. The median duration of therapy with lonafarnib was 8 weeks (range, 2-41 wks). RESULTS: Two patients responded. One patient in the accelerated phase of CML returned to the chronic phase, a response that lasted for 3 months. Another patient with chronic phase disease had lowering of the leukocyte count without the need for hydroxyurea and normalization of the differential count that lasted for 5 months. The most common adverse event was diarrhea, which was noted in 11 patients (84%) (Grade > or = 3 in 4 patients; 31%; toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Therapy was discontinued in one patient because of diarrhea not responding to dose adjustments. CONCLUSIONS: Single-agent lonafarnib appears to have clinical activity in a small proportion of patients with CML refractory to imatinib.

Adult↗

PubMed1994

The Y chromosome-linked "autoimmune accelerating" yaa gene suppresses collagen-induced arthritis.

The Y-linked autoimmune accelerating gene mutation (yaa), first discovered in the BXSB mouse strain, is known to accelerate spontaneous autoantibody production and subsequent development of lupus disease. We have investigated the role of the yaa gene in the development of the type II collagen (CII)-induced arthritis (CIA), which is used as a model for rheumatoid arthritis. In contrast to the accelerating effects on development of lupus autoimmunity we can show that the presence of BXSB Y chromosome carrying the yaa gene block development of CIA in F1 crosses with three normally CIA-susceptible strains, DBA/1, C3H.Q and B10.Q. Backcross experiments showed an additional modulatory effect from other BXSB genes or possibly from DBA/1 X chromosome. To evaluate the effect mediated by the yaa gene alone, the BXSB Y chromosome was bred into the DBA/1 gene background. The DBA/1 congenic DBA/1.yaa male mice were less susceptible to arthritis development than their DBA/1 counterparts. (B10.QxDBA/1.yaa)F1 acquired resistance to arthritis development similar to that of DBA/1.yaa, indicating a role for the yaa gene alone. The serum levels of autoantibodies to CII were significantly suppressed in all strains carrying yaa. In DBA/1.yaa mice a reduced number of T cells were found to produce interferon-gamma after in vitro stimulation with CII. Thus, although autoreactive B cells are important in both diseases they play different roles in murine lupus and in CIA.

Animals↗

PubMed1996

Mapping of the domains required for decay acceleration activity of the human factor H-like protein 1 and factor H.

The human factor H-like protein 1 (FHL-1) is composed of seven repetitive elements (short consensus repeats; SCR) that are identical in sequence to the seven N-terminal SCR of complement factor H. We show that the FHL-1 protein has decay acceleration activity in that it can dissociate C3/C5-convertases bound to the surface of sheep red blood cells. The same activity was also determined for factor H. However, compared to FHL-1, factor H was more efficient in decay acceleration, as about 100-fold less protein was required for a 50% inhibition of activity. The domain required for decay accelerating activity of FHL-1 and factor H was mapped by the use of recombinant fragments. FHL-1 and a series of truncated forms of the protein were expressed in the baculovirus system. Recombinant FHL-1 and all mutants which include SCR 1-4 were functionally active. These four N-terminal SCR are essential and sufficient for activity, as deletion mutants which lack SCR 1 or SCR 4 showed no activity. These results demonstrate that FHL-1 and factor H have identical and overlapping regulatory functions in the complement system and that the domain required for this activity is located in the overlapping region of both proteins within the N-terminal four SCR.

Animals↗

PubMed1983

Mutagenic evaluations of four rubber accelerators in a battery of in vitro mutagenic assays.

The mutagenic/carcinogenic potential of four commercial accelerators were evaluated using a battery of in vitro assays. All of these compounds were mutagenic in one or more assays. Positive responses were noted in the Escherichia coli pol A+/pol A- DNA repair, mouse lymphoma L5178Y TK+/- forward mutation, BALB/3T3 cell transformation, and CHO cell chromosome aberration assays. In contrast to previous studies of accelerators, no mutagenic response was observed in the E coli WP2 uvrA- assay or in any of the Salmonella typhimurium strains tested. These studies have indicated that rubber accelerators should be regarded as potential human health hazards and that further in vitro and in vivo studies are needed to assess the potential genetic hazards of this large class of chemicals.

Benzothiazoles↗

PubMed2001

Accelerated hyperfractionated irradiation for advanced head and neck cancer: effect of shortening the median treatment duration by 13 days.

BACKGROUND AND PURPOSE: Optimal treatment duration of altered fractionation schedules in head and neck cancer is still undefined. A retrospective study on local tumor control, survival, and complications of accelerated hyperfractionated irradiation in head and neck cancer was undertaken to investigate whether there was an advantage in further shortening overall time from 6.5 weeks. METHODS: Four hundred nineteen consecutive male patients treated with radiation alone for cure 1987-1998 were analyzed. Patients with stage I, or treated also with brachytherapy implants or chemotherapy, were excluded. Treatment with accelerated hyperfractionation was performed twice daily, at a median of 1.6 Gy/fraction, to a total median dose of 68 Gy in 39 days. The patient population was divided into two groups: those with < or =39 days overall treatment time (group A, n = 227; median, 33 days) and those with >39 days (group B, n = 192; median, 46 days). Group A received a significant median tumor dose reduction of 7% compared with group B. RESULTS: The 7-year actuarial local control (LC) rates were 59% and 48% for groups A and B, respectively (p =.02). The actuarial LC rates for T1-2 patients were 79% and 74% at 7 years for groups A and B, respectively (p = NS). Similarly, for T3-4 patients, they were 47% and 35% (p =.02), respectively. The 7-year actuarial disease-free survival (DFS) rates for groups A and B were 39% and 26% (p =.01), respectively. For stage II patients, DFS was 62% and 60% at 7 years (p = NS) for groups A and B, respectively. And similarly, for stage III-IV patients, DFS was 33% and 20% (p =.04), respectively, at 7 years. LC and DFS rates at 7 years for T4 and stage IV patients, respectively, were significantly improved in group A. Cox regression analyses for LC showed that both T stage and overall time were significant prognostic factors. Similarly, UICC clinical stage and overall time were significant prognostic factors for DFS. There was no difference in acute morbidity between the two groups: 3% of patients in both groups required tube or parenteral feeding. The 7-year actuarial probability of RTOG/EORTC grades 3-5 late effects was 15% and 13%, respectively, for each group (p = NS). CONCLUSIONS: This study, with the limitations of a retrospective study, has shown a significant improvement in local tumor control and disease-free survival, in patients treated with shorter overall treatment times (median, 33 days) with an accelerated hyperfractionated irradiation schedule compared with those treated with a median duration of 46 days. No significant enhancement of acute reactions and late morbidity were observed with the shorter schedule.

Adult↗

PubMed2005

Suppression of accelerated tumor growth in surgical wounds by celecoxib and indomethacin.

BACKGROUND: Tumor growth is accelerated in surgical wounds. However, few experiments seeking to prevent such accelerated tumor growth have been performed. METHODS: We created surgical wounds in three syngeneic mice for the implantation of three murine cancer cell lines, SCC VII, CT-26, and B16F10. The tumor growth in the wound group was compared with that in non-wound-control mice. Celecoxib or indomethacin was administered to the mice that had tumor implanted into the surgical wound to observe the tumor-suppressive effect. RESULTS: The surgical wounds promoted tumor growth with different degrees, depending on the type of tumor. Such an accelerated tumor growth did not seem to be affected by cyclooxygenase-2 expression of tumors per se, but its mechanism needs to be explained by further studies. Celecoxib and indomethacin had a significant inhibitory effect on the tumor growth in the surgical wound. This suppressive effect is most obvious when celecoxib is administered daily from 1 day before surgical wounding and tumor implantation. CONCLUSION: Our results can justify that the preventive use of celecoxib in patients in whom local recurrence by tumor contamination is predicted.

Animals↗

PubMed2007

Acceleration of hyperfractionated chemoradiation regimen for advanced head and neck cancer.

BACKGROUND: Our aim was to evaluate the acceleration of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m(2)/day and 5-fluorouracil 600 mg/m(2)/day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid-treatment 1-week break. RESULTS: Forty-six patients with T3-4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was -3.8% and -7.9%, respectively (p = .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease. CONCLUSIONS: In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during therapy in most patients.

Adult↗

PubMed1994

A fetal rat urogenital sinus mesenchymal cell line (rUGM): accelerated growth and conferral of androgen-induced growth responsiveness upon a human bladder cancer epithelial cell line in vivo.

A cell-cell interaction model was developed to examine the intercellular communication between mesenchymal and epithelial cells in vivo, and to define the role of androgen and paracrine growth factors in promoting growth and differentiation of the target epithelial cells. Using this model system, we have demonstrated that, in the presence of androgenic steroids, a fetal urogenital sinus mesenchymal cell line exhibited androgen-induced growth responses which resulted in an induction of growth of a non-androgen target epithelial cell line derived from human urinary bladder. Our results show that: (1) a rat fetal urogenital sinus mesenchyme-derived cell line (rUGM) accelerated growth and conferred androgen-induced growth responsiveness upon a non-androgen target cell line, WH, derived from a human bladder transitional-cell carcinoma (TCC); this induction of epithelial tumor growth in vivo occurred in a fibroblast-specific manner; (2) live fetal rUGM cells are required to promote WH tumor growth in vivo, which suggests that continuous production of factors that may serve as mediators for paracrine/autocrine pathways are responsible for androgen stimulation of WH tumor growth in vivo; and (3) although WH tumor growth, mediated by the presence of rUGM cells, was markedly accelerated by the presence of androgen in vivo, androgen and rUGM cells failed to promote the expression of a human prostate-specific antigen (PSA) by WH tumors in vivo. Our results emphasize the importance of organ-specific fibroblasts that promote tumor growth and mediate androgen-induced growth responses; the accelerated growth of the bladder epithelium was not accompanied by the expression of PSA, a known differentiated gene product produced by human prostatic epithelial cells. This report also discusses the potential significance of mesenchymal-epithelial cellular interaction which mediates androgen action and may play an important role by influencing human prostate tumor growth, progression and differentiation.

Aged↗

PubMed1985

Nuclear mutation leads to an accelerated turnover of chloroplast-encoded 48 kd and 34.5 kd polypeptides in thylakoids lacking photosystem II.

We have studied the synthesis and accumulation of a chloroplast-encoded 48 kd chla-reaction center protein and the 34.5 kd ;atrazine binding' protein in a nuclear maize mutant which fails to assemble photosystem II reaction centers. The failure of these polypeptides to accumulation in mutant thylakoids is not due to direct nuclear control over their synthesis but is rather due to their specific, accelerated turnover from the thylakoid membrane. The accelerated turnover of these polypeptides in mutant thylakoids is largely independent of illumination conditions, as accelerated turnover occurs in the dark as well as in the light. In contrast to wild type, the 48 kd and 34.5 kd polypeptides are preferentially associated with stroma, rather than grana, lamellae in mutant membranes, suggesting that turnover occurs before these polypeptides become enriched in the grana. The nucleus thus plays a role in the stabilization of these chloroplast-encoded photosystem II reaction center polypeptides.

Journal Article↗

PubMed1989

A preliminary durability study of two types of low-profile pericardial bioprosthetic valves through the use of accelerated fatigue testing and flow characterization.

Bioprosthetic heart valves are being used more often because of certain advantages they have over artificial valves. The bioprostheses are less thrombogenic, cause a lower incidence of hemolysis, and usually fail in a slow progressive manner. A combination of flow characterization and accelerated testing was used to assess the durability of two types of pericardial valves, the Ionescu-Shiley Low Profile Mitral and the Carpentier-Edwards Low Profile Aortic valve. The flow characterization work was done in an aortic chamber designed for in vivo simulation. The function of the valve was monitored between different stages of the accelerated testing using laser Doppler anemometry. Accelerated testing was performed at 1300 cardiac cycles per minute, and physiologic conditions both in closing pressures and the ambient temperature were maintained. Results indicated a change in flow characteristics owing to cyclic loading of the leaflet tissue. The flow orifice increased over time leading to a decrease in peak velocity. Future developments in Doppler ultrasound may facilitate non-invasive assessment of these peak velocity variations. Calcification of the tissue was not considered, since this was an in vitro study.

Aortic Valve↗

PubMed2004

Transforming growth factor-beta1 accelerates bone bonding to a blended calcium phosphate ceramic coating: a dose-response study.

In vivo strain measurements can facilitate the study of the bone remodeling response to loading and load changes. Calcium phosphate ceramic (CPC) coatings have been used to attach strain gauges to bone for extended periods of time, but require up to 12 weeks for adequate CPC-to-bone bonding. Transforming growth factor beta 1 (TGF-beta1), an osteoinductive growth factor, was used as a surface enhancement to accelerate bone growth and bonding to CPC particles. The aim of this study was to find an optimal dosage of TGF-beta1 to accelerate the attachment process. CPC-coated strain gauges were enhanced with doses of 0.5, 1.0, or 2.0 microg of TGF-beta1 per gauge. Gauges were placed on the femora of dogs, which were exercised daily and fed ad libitum. After 3, 6, and 12 weeks, gauge attachment was quantitatively assessed using mechanical testing and histomorphometry. Gauge attachment was also qualitatively assessed using back scatter electron microscopy. Agreement of the mechanical test results with both the back scatter electron microscopy images and histomorphometry results showed that the 1.0 microg per gauge dose of TGF-beta1 is an optimal dose to accelerate bone formation and attachment to CPC-coated strain gauges.

Animals↗

PubMedDate not supplied

Acceleration time in cerebral arteries of preterm and term infants.

We measured the acceleration times in the pericallosal, internal carotid, and basilar arteries with two-dimensional/pulsed Doppler ultrasonography in 145 nondistressed preterm and term infants between 24 and 48 hours after birth. In all three arteries we found a linear relationship between the acceleration time and menstrual age or birth weight. These findings were determined by changes in peak systolic flow velocity, but not by changes in mean arterial blood pressure or cardiac output. We speculate on an important role for cerebral autoregulation in the acceleration time variations between newborn infants of differing menstrual ages and birth weights.

Birth Weight↗

PubMed1979

Effects of accelerating stimulation on different indices of development in Japanese quail embryos.

Effects of continuous accelerating stimulation on the timing, duration and rate of occurrence of different indices of development in Japanese quail embryos were examined. Indices used were: the onset of breathing and hatching, also pipping, clicking, vocalisation, membrane penetration, yolk sac withdrawal and lung aeration. Results showed that embryos stimulated by clicks began breathing about nine hours in advance of unstimulated controls and hatched about 23 hours in advance. All other indices occurred early in comparison with controls but not all occurred at the same accelerated rate and some having begun early, proceeded at the same rate as controls then were completed rapidly just before hatching. Developmental problems are discussed in the light of these results and it is suggested that continuous accelerating stimulation affects development in two main stages.

Animals↗

PubMed1984

A nerve-conditioning lesion accelerates limb regeneration in the newt.

A nerve-conditioning lesion induced sustained acceleration of limb regeneration. Newt limb nerves were subjected to a conditioning lesion by unilateral axotomy at the elbow 2 weeks prior to amputating both limbs above the elbows. Limbs on the side that had received a conditioning lesion began the regeneration process 3-4 days earlier than contralateral controls and this difference was observed up to recognizable digit formation. Limb buds on the conditioned sides had a twofold greater axonal density than contralateral counterparts at 2 weeks after amputation. Since limb bud formation is dependent on a sufficient quantity of axonal regrowth, accelerated limb regeneration is apparently due to accelerated reinnervation.

Amputation, Surgical↗

PubMed1989

Identification of puberty-accelerating pheromones in male mouse urine.

Gas chromatography-mass spectrometry was employed to identify the two volatile amines in male mouse urine. These amines were much less concentrated in urine of castrated males. The identified amines, isobutylamine and isoamylamine, were assayed for the potential of puberty acceleration in postweaning female mice. A total of 105 young female mice were exposed to one of the following five odors: distilled water (control), 0.1 M isobutylamine, 0.1 M isoamylamine, a mixture of 0.05 M isobutylamine and 0.05 M isoamylamine, or fresh male mouse urine. The mixture of these amines accelerated the vaginal opening of young females. Except for the control, all experimental odors accelerated the first vaginal estrus in ICR strain mice.

Amines↗