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J Blank

Publications and source records attributed to J Blank.

At least 19 recordsLinked to original sources
PubMed2006

Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network.

BACKGROUND: There is no standard first line treatment for mantle cell lymphoma. PATIENTS AND METHODS: This was a multicenter phase II pilot study of rituximab and modified hyper-fractionated cyclophosphamide, vincristine doxorubicin, dexamethasone (modified R-hyperCVAD) administered every 28 days for four to six cycles followed by rituximab maintenance therapy consisting of four weekly doses every 6 months for 2 years. Unlike traditional hyperCVAD regimens, no methotrexate or cytarabine was administered. RESULTS: Of 22 patients, the overall response rate was 77% and the complete response rate was 64%. With a median follow-up time of 37 months in surviving patients, the median PFS was 37 months and the median OS was not reached. The achievement of a molecular remission did not correlate with improved outcome. The major toxicity was expected myelosuppression. Two patients died during induction treatment. There were no major adverse effects during maintenance therapy. CONCLUSION: In a multicenter trial, modified R-hyperCVAD was tolerable and effective induction therapy for untreated MCL. Maintenance rituximab appeared to prolong PFS without increasing toxicity.

Adult↗
PubMed2006

Piezosurgery--a new safe technique in cranial osteoplasty?

All surgical interventions on the neurocranium bear the risk of injury of the dura mater and development of a cerebrospinal fluid fistula. Therefore, despite careful preparation, damage to the dura mater cannot always be omitted. Especially after surgery and in patients with increased intracranial pressure (craniosynostoses) there is a high risk of perforating the dura. In this article a new surgical technique for osteotomy (Piezosurgery) that avoids perforation of the dura is presented. Ultrasonic microvibrations allow a selective cut of only mineralized structures without damage to the soft tissue. Even in case of accidental contact the dura remains undamaged. This advantage is also useful for bone splitting, to separate the tabula externa from the tabula interna in situ, without any risk of dura perforation even in case of the very thin bones in an infantile skull. The present work shows the applicability of piezoelectric surgery in high-risk patients after osteotomy, avoiding perforation of the dura mater.

Brain Injuries↗
PubMed2003

The influence of His94 and Pro149 in modulating the activity of V. cholerae DsbA.

DsbA is the primary catalyst of disulfide bond formation in the periplasm of gram-negative bacteria. Numerous theoretical and experimental studies have been undertaken to determine the molecular mechanisms by which DsbA acts as a potent oxidant, whereas the homologous cytoplasmic protein, thioredoxin, acts as a reductant. Many of these studies have focused on the nature of the two residues that lie between the active-site cysteines. Although these are clearly important, they are not solely responsible for the differences in activity between these thiol-disulfide oxidoreductases. Q97 in the helical domain of E. coli DsbA has been implicated in influencing the redox potential of E. coli DsbA. In V. cholerae DsbA, the analogous residue is H94. In this study, the effect of H94 on the oxidase activity of DsbA is examined, along with the role of the conserved cis-proline residue P149. The DsbA mutant H94L shows a nearly fourfold increase in activity over the wild-type enzyme. To our knowledge, this is the first time an increase in the normal activity of a thiol-disulfide oxidoreductase has been reported. Potential reasons for this increase in activity are discussed.

Histidine↗
PubMed2000

Inclusion of older women in randomized clinical trials: factors associated with taking study medication in the fracture intervention trial.

OBJECTIVES: The purpose of this study is to describe the early study medication discontinuation (SMD) experience during the first year of follow-up in a randomized clinical trial in older women and to determine the associations between various baseline characteristics and risk of SMD. DESIGH, SETTING, AND PARTICIPANTS: The authors studied 6,459 postmenopausal women aged 55 to 80 from 11 clinical settings during their first year of participation in the Fracture Intervention Trial (FIT). This trial was designed to test the efficacy of alendronate (Fosamax) on fracture prevention among women with low bone mass. RESULTS: Study medication discontinuation was greatest in the first month post-randomization (2.2%) and declined thereafter. Cumulative rates of study medication discontinuation were 4.8% (n = 311) at 3 months and 11.1% (n = 717) at 12 months. SMD was not associated with age, marital status, alcohol consumption, regular exercise, past estrogen replacement therapy use, bone mineral density, or personal or maternal fracture history. After adjusting for covariates and markers of comorbidity, the strongest predictor of SMD was fair-to-poor self-rated health (relative risk (RR) 2.10; 95% confidence interval (CI) 1.47, 2.99). Having four or more depressive symptoms was also a significant predictor and had a risk associated with SMD (RR vs none 1.34; 95% CI 1.05, 1.71) similar to that seen for individuals with good self-rated health (RR 1.49; 95% CI 1.16, 1.91). CONCLUSIONS: Results from this cohort emphasize that clinical trials in older women with multiple concomitant conditions can achieve high levels of adherence. Thought should be given to measuring self-rated health and depressive symptoms before randomization to help identify individuals to be targeted for special assistance programs that focus on encouraging adherence.

Aged↗
PubMed1999

A comparison of two controlled-release delivery systems for the delivery of amiloride to control angiogenesis.

The diuretic amiloride has been reported to inhibit both Na+-H+ antiport and the urokinase-type plasminogen activator. As a consequence of these inhibitions, neovascularization may also be inhibited. We hypothesized that if amiloride could be effectively delivered in a site-specific manner, a system might be developed that could inhibit localized angiogenesis. In order to evaluate this possibility we conducted a study that compared two different controlled-release systems into which amiloride had been incorporated. The effectiveness of amiloride release from each delivery system was determined by quantitating angiogenic patterns in a chick chorioallantoic membrane (CAM) system using a fractal analysis software program. The two delivery systems compared were sucrose acetate isobutyrate (SAIB) and calcium alginate. Initial HPLC laboratory tests confirmed that amiloride could be released from both SAIB and calcium alginate in vitro in a sustained manner for 72 h. The CAM studies confirmed that neither SAIB nor calcium alginate alone promoted or inhibited angiogenesis when compared to nontreated controls. The release of amiloride from each delivery vehicle resulted in a significant (P < 0.05) inhibition of angiogenesis following both 24 and 48 h of release compared to controls. There was no difference in inhibition of angiogenesis, however, when comparing SAIB + amiloride treated CAMs with calcium alginate + amiloride treated CAMs. These data suggest that both SAIB and calcium alginate may be useful delivery vehicles for the localized application of amiloride to control angiogenesis. Such a system could potentially control tumor angiogenesis without systemic effects.

Alginates↗
PubMed1998

Mailing strategies and costs of recruiting heavy smokers in CARET, a large chemoprevention trial.

Recruitment costs represent a major portion of the budget for large clinical trials during the initial years of the study. Further, the rate of recruitment affects allocation of resources in future years. To learn about the costs and yields of recruiting from different populations and under different mailing strategies, we monitored recruitment yields of eligible heavy smokers for the Carotene and Retinol Efficacy Trial (CARET) at the Portland Study Center. Yields from the mailings, measured by response rate, percent of potential participants randomized, and related costs per randomization varied both by mailing strategy and by population targeted. Yield and cost varied significantly across population sources. Less variation was observed among various mailing strategies. Tracking the recruitment process yield provided useful information that allowed us to adjust recruitment approaches and achieve our randomization goals quickly and economically.

Aged↗
PubMed1996

Elongation factor Ts from Thermus thermophilus-- overproduction in Escherichia coli, quaternary structure and interaction with elongation factor Tu.

The gene encoding the elongation factor Ts from Thermus thermophilus was sequenced, cloned and the protein overproduced in Escherichia coli. In comparison to the EF-Ts from E. coli with 282 amino acid residues, EF-Ts from T. thermophilus is considerably shorter, differing by 86 amino acids. EF-Ts from the thermophile is stable at high temperatures, which facilitates its separation from E. coli proteins. Purified T. thermophilus EF-Ts forms a homodimer with a disulfide bridge between the two cysteine residues at position 190. The modification of Cys19O by iodoacetamide affects neither the dimerization nor the ability of EF-Ts to facilitate the nucleotide exchange of elongation factor Tu. The disulfide bridge was detected only in purified EF-TS, but not in protein extracts immediately after cell disruption. The physiological role of this disulfide bridge remains, therefore, unclear. Besides the quaternary (EF-TU . EF-Ts)2 complex, a ternary EF-TU . EF-Ts2 complex was detected by gel permeation chromatography and polyacrylamide gel electrophoresis. Trypsin cleavage after Lys48 or modification of Cys78 yield inactive EF-Ts, that does not bind to EF-Tu but is still capable of forming homodimers.

Amino Acid Sequence↗
PubMed1995

Overexpression and purification of Thermus thermophilus elongation factors G, Tu, and Ts from Escherichia coli.

The translation elongation factors G (EF-G), Tu (EF-Tu), and Ts (EF-Ts) from the extreme thermophilic bacterium Thermus thermophilus were overproduced in Escherichia coli. The fus gene coding for EF-G and the tufA gene coding for EF-Tu were expressed under the control of a tac promoter, whereas EF-Ts was overproduced with the T7 RNA polymerase system. A detailed description for the purification of the three elongation factors from E. coli is presented. EF-G and EF-Tu are isolated by Q-Sepharose FF chromatography, heat treatment at 65 or 60 degrees C, respectively, and Sephacryl S200 gel permeation chromatography. For the purification of EF-Ts, a heat denaturation step is followed by DEAE-cellulose chromatography and a cation exchange EMD-SO-3 650 column. The overproduced factors show the same properties as those purified from T. thermophilus. As the crystal structures of T. thermophilus EF-Tu and EF-G have been solved recently, many questions concerning the function of particular residues or domains arise, which may be best addressed by studying the in vitro behavior and structure of altered recombinant constructs. The methods presented here should facilitate such studies.

Bacteriophage T7↗
PubMed1994

Autoimmune hemolysis following transfusion: a mimicking autoanti-D in a D- patient with alloanti-D.

An 80-year-old group O, D- (rr) female with anti-C, -D, -E, and -Fya received four units of crossmatch-compatible red blood cells (RBCs). The direct antiglobulin test (DAT) was negative. Two weeks later, jaundice, dark urine, a 16% drop in hematocrit (Hct), a 20% reticulocyte count, and absent haptoglobin occurred. During the next month, her DAT was positive with anti-IgG and -C3d. Acid eluates, which repeatedly showed anti-D specificity, were nonreactive with enzyme-treated D- RBCs. Adsorption with D- RBCs reduced reactivity. An eluate from the adsorbing D- RBCs was nonreactive with D+ KBCs. These findings suggest an autoantibody mimicking alloanti-D. The patient was treated with prednisone and was transfused with group O, D- (rr), K-, Fy(a-) RBCs. Four months later, the Hct was stable. One year later, the DAT remained positive and the eluate demonstrated a panagglutinin.

Journal Article↗
PubMed1993

Depletion of olfactory bulb norepinephrine by 6-OHDA disrupts chemical cue but not social recognition responses in male rats.

In the present experiment, 6-OHDA was infused directly into the olfactory bulb (OB) to produce a localized neurotoxic lesion. Habituation/dishabituation behavioral tests were then conducted to measure recognition responses to chemical cues (urine as a stimulus) and to social stimuli (ovariectomized rat as a stimulus). Infusion of 6-OHDA resulted in a near complete depletion of OB-norepinephrine (NE), whereas it had little effect (15% reduction) on OB dopamine (DA) contents. Nor were any significant effects on hypothalamic, hippocampal, olfactory tubercle, and corpus striatal NE and DA contents observed. Behaviorally, dishabituation responses to chemical cues were greatly impaired, however, there was relatively little effect on social behavior dishabituation responses. These results demonstrate that 6-OHDA can be used to produce a near complete but localized depletion of OB-NE. This treatment impairs dishabituation responses to chemical cues but not social stimuli indicating that OB-NE appears necessary for processing of chemical cue, but not social memory recognition process.

Animals↗
PubMed1993

Selection for active E. coli tRNA(Phe) variants from a randomized library using two proteins.

In vitro selection was used to isolate active Escherichia coli tRNA(Phe) variants from randomized libraries. Functional tRNAs were first selected by multiple rounds of binding to Escherichia coli phenylalanyl-tRNA synthetase. These variants were then aminoacylated and selected for affinity to elongation factor-Tu. By randomizing potential recognition nucleotides, the importance of residues U20, G34, A35, A36 and U59, previously identified to be required for specific recognition by E. coli phenylalanyl-tRNA synthetase (FRS), was confirmed. However, the sequences of several active variants imply that the wild-type tertiary interactions G10-C25-U45 and A26-G44 are not required for recognition, as previously suggested. Selection of functional tRNAs from a second library randomized at positions normally involved in conserved tertiary interactions revealed new combinations of nucleotides at these positions, suggesting the presence of novel tertiary interactions. In both libraries, active sequences containing deletions were isolated. Taken together, it is clear that FRS is active with substrates having an unexpectedly broad sequence diversity. Finally, the potency of this method is illustrated by the identification of a second class of variants that was isolated by virtue of the presence of an impurity in the FRS preparation.

Base Sequence↗
PubMed1992

Relaxation therapy reduces anxiety in child and adolescent psychiatric patients.

The immediate effects of relaxation therapy (RT) were assessed in 40 hospitalized children and adolescents with diagnoses of adjustment disorder and depression. These effects were assessed using a within subjects pre-test/post-test design and by comparison with a control group of 20 depressed and adjustment disorder patients who watched a 1-h relaxing videotape. The 1-h RT class consisted of yoga exercise, a brief massage and progressive muscle relaxation. Decreases were noted in both self-reported anxiety and in anxious behavior and fidgeting as well as increases in positive affect in the RT but not the video group. In addition, adjustment disorder patients and a third of the depressed patients showed decreases in cortisol levels following RT, while no changes were noted in the video group. Thus, both diagnostic groups appeared to benefit from the RT class.

Adjustment Disorders↗
PubMed1988

Nitrogen-dioxide-induced emphysema in rats. Lack of worsening by beta-aminopropionitrile treatment.

We evaluated the effect of beta-aminopropionitrile (beta APN) on the nitrogen dioxide (NO2) animal model of emphysema. Rats maintained on a beta APN-supplemented or a regular diet were exposed to 30 ppm NO2 for intervals ranging from 1 to 8 wk. Emphysema development was assessed by histologic evaluation and by changes in lung volume and mean linear intercept values. Evidence of pathologic changes were also documented by clinical and radiographic findings of osteolathyrism. The induction of centriacinar emphysema was attributed specifically to NO2 exposure. Neither the severity of the emphysema nor the time course of its development was altered by the beta APN-supplemented diet. These findings are in marked contrast to those observed with the exogenous elastase model of the disease, and they suggest that elastin synthesis and repair may not modulate elastin destruction in the NO2 model of emphysema.

Aminopropionitrile↗
PubMed1987

Neutrophil recruitment and degranulation during induction of emphysema in the rat by nitrogen dioxide.

Rats exposed to 30 ppm NO2 continuously for 3 to 6 wk developed mild centriacinar air-space enlargement and mild interstitial fibrosis. The emphysematous changes did not become more severe after 6 wk with continued NO2 exposure for as long as 14 additional weeks. Elastase inhibitory capacity (EIC) and the total protein concentration increased acutely in lung lavage fluid, consistent with the histologic evidence of pulmonary edema, then subsided but remained above control levels for the entire exposure period. The ratio of EIC to total protein remained unchanged relative to that in control animals. Neutrophils accumulated in the lung and were recoverable by lavage with the same relative concentration profile as observed for total protein. The average elastase activity per neutrophil in cells recovered from the air space by lung lavage was 60% less than in cells recovered from peripheral blood. This was true for control or NO2-exposed rats. Thus, emphysematous changes in the NO2-exposed rat were accompanied by a marked neutrophil recruitment concomitant with an increased neutrophil elastase burden in the lung, which may have directly contributed to lesion development.

Animals↗