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Biomedical subjects

J Rush

Publications and source records attributed to J Rush.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pathological gambling in Louisiana: an epidemiological perspective.

A review of telephone interview data using the South Oaks Gambling Screen on a random sample of 1,818 Louisiana residents > 18 years indicated that 4.8% of adults > 21 years (approximately 122,500) have gambling disorders, compared to 14.4% of 18 to 21 year olds (approximately 21,000). Geographic distribution of gambling disorders shows equal statewide penetrance. Pathological gamblers are demographically distinct, more likely to be male, < 30 years, non-Caucasian, unmarried, and less likely to have graduated from high school than nonproblem gamblers. Two demographic clusters, males < 21 who primarily wager on video poker and those > 30 who primarily wager on horse racing, were noted. Data is needed on adolescent incidence and prevalence to plan prevention and early intervention programs in Louisiana.

Adolescent↗
PubMed1995

Facile, in situ matrix-assisted laser desorption ionization-mass spectrometry analysis and assignment of disulfide pairings in heteropeptide molecules.

During a routine analysis of disulfide-linked synthetic heterodipeptides by matrix-assisted laser desorption ionization (MALDI) mass spectrometry with linear detection we observed not only the expected mass of the dipeptide, but also the mass of the individual constituent monomer peptides. This was surprising because the peptide was purified as an intact dipeptide and no overt attempt was made to reduce the disulfide linkage before mass analysis. In contrast, analysis of the same sample by electrospray ionization mass spectrometry gave the mass of the dipeptide only. To investigate this further, two additional model heterodipeptides were prepared and all three were used to systematically study several matrix-assisted laser desorption ionization mass spectrometry parameters. These parameters were three different matrices (alpha-cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic acid, and sinapinic acid), both positive and negative modes of detection, and varying the acceleration voltage from 5 to 20 kV. Except for the sinapinic acid matrix where poor-quality spectra were obtained, all three model heterodipeptides fragmented under the tested conditions in a manner consistent with the cleavage of disulfide bonds, although the absolute level was sample dependent. The precise mechanism of disulfide cleavage during analysis is unknown, but the cleavage we observed appears to originate during the initial ionization event. Because the MALDI process involves irradiating samples with a laser, the fragmentation of disulfide-linked peptides that we observe bears some resemblance to light-induced homolytic cleavage of aqueous solutions of the amino acid cystine, although other mechanisms for fragmentation are also possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Purification and characterization of colicin V from Escherichia coli culture supernatants.

The peptide antibiotic, colicin V (ColV), has been purified and characterized from Escherichia coli culture supernatants by precipitation with trichloroacetic acid (TCA) and high-performance liquid chromatography (HPLC). Polyacrylamide gel electrophoresis (PAGE) and Western analysis identifies ColV as a polypeptide with an apparent molecular mass of 5.8 kDa. The protein identified remains biologically active after purification and SDS-PAGE. A mutant form of ColV, ColV-1, removes the carboxy-terminal 21 amino acids and replaces them with eight heterologous residues. The ColV-1 mutant is also secreted into the extracellular medium, demonstrating that the carboxy-terminal 21 amino acids are not required for secretion by the dedicated ColV export system, CvaAB/TolC. N-Terminal amino acid sequencing shows that the primary translation product of cvaC, the ColV structural gene, is processed to remove the N-terminal 15 amino acids. The cleavage site is preceded by the sequence Ser-Gly-Gly, making it a potential substrate for leader peptidase. The ColV leader sequence has many characteristics in common with the amino-terminal leader sequences of the lactococcins, lactacins, and pediocins from Gram-positive bacteria. Mass spectroscopy of purified ColV shows that it has a mass of 8741.0 amu, consistent with the mass of the unmodified 88 amino acid polypeptide. The purification scheme provides a rapid and simple way to obtain ColV for further biochemical analysis.

Amino Acid Sequence↗
PubMed1994

Effects of scalaradial, a novel inhibitor of 14 kDa phospholipase A2, on human neutrophil function.

Scalaradial, a marine natural product with anti-inflammatory activity, has been shown to be a selective inhibitor of 14 kDa type II phospholipase A2(PLA2). We have examined the inhibition by scalaradial (0.1 nM to 10 microM) of neutrophil function (degranulation) in response to receptor-mediated activation [N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), 30 nM; leuokotriene B4 (LTB4), 100 nM; platelet-activating factor (PAF), 100 nM] and non-receptor-mediated stimuli [A23187 (1 microM) and thapsigargin (100 nM)]. Furthermore, we evaluated the ability of scalaradial to inhibit the increase in intracellular Ca2+ in response to fMLP, LTB4, A23187, and thapsigargin as well as its ability to prevent either fMLP- or LTB4-mediated elevation in inositol phosphate production (InsP). Scalaradial was a potent inhibitor of both receptor- (IC50 = 50-200 nM) and non-receptor- (IC50 = 40-900 nM) mediated degranulation. Although scalaradial inhibited the mobilization of Ca2+ induced by fMLP, LTB4, and PAF, it did not affect the maximal Ca2+ levels attained with A23187 or thapsigargin. Neutrophil-binding studies with [3H]fMLP and [3H]LTB4 would suggest that the effect of scalaradial on agonist-induced degranulation and increase in intracellular Ca2+ was not at the receptor level because 50-fold higher concentrations were required to have a significant effect on the binding of these agonists. To determine if scalaradial affected phosphatidylinositol selective phospholipase C (PI-PLC) activity, assays were conducted to monitor fMLP- and LTB4-induced formation of InsPs using myo-[3H]inositol-labeled U-937 cells. In these cells, 2.5 to 9-fold higher concentrations of scalaradial were required to inhibit PI-PLC activity than to inhibit agonist-induced degranulation of neutrophils, suggesting that the effects of scalaradial on Ca2+ and degranulation are not the sole result of blocking receptor activation of PI-PLC. Results obtained with receptor-mediated stimuli suggest that scalaradial may have direct effects on Ca2+ channels and InsP turnover, but inhibition of intracellular Ca2+ levels was not required for scalaradial to block degranulation since scalaradial was capable of inhibiting degranulation produced by either A23187 or thapsigargin, without changing the maximal Ca2+ levels obtained with these two stimuli. These results demonstrate that scalaradial can inhibit degranulation in the presence of micromolar intracellular Ca2+ concentration, thus supporting the hypothesis that a 14 kDa PLA2 may be important in the regulation of neutrophil degranulation.

Anti-Inflammatory Agents↗
PubMed1994

In vivo phosphorylation site of hexokinase 2 in Saccharomyces cerevisiae.

Yeast hexokinase 2 is known to be a phosphoprotein in vivo, prominently labeled from 32P-inorganic phosphate after a shift of cells to medium with low glucose concentration [Vojtek, A. B., & Fraenkel D. G. (1990) Eur. J. Biochem, 190, 371-375]. The principal and perhaps sole site of phosphorylation is now identified as residue serine-15, by observation of a single tryptic peptide difference, its sequencing and size determination by mass spectrometry, and by mutation to alanine, which prevents phosphorylation in vivo. Although protein kinase A was unlikely to accomplish the phosphorylation in vivo, serine-15 does belong to a protein kinase A consensus phosphorylation sequence, and in vitro phosphorylation by protein kinase A at serine-15 could be shown by labeling and by peptide determination. The alanine-15 mutant enzyme was not phosphorylated in vitro.

Amino Acid Sequence↗
PubMed1994

Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients.

In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% effective concentrations, < 2 micrograms/ml for acyclovir and < 100 micrograms/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.

Acyclovir↗
PubMed1993

Formins: phosphoprotein isoforms encoded by the mouse limb deformity locus.

Mutations at the mouse limb deformity (ld) locus result in defects of growth and patterning of the limb and kidney during embryonic development. The gene responsible for this phenotype is large and complex, with the capacity to generate a number of alternatively spliced messenger RNA transcripts encoding nuclear protein isoforms called "formins." We have made polyclonal antibodies to specific formin peptides and have confirmed the authenticity of the antibodies' reactivity, using cell lines derived from mice with molecularly defined mutations at the ld locus. In addition, we have used these antibodies to detect and characterize polypeptides encoded by both wild-type and mutant ld alleles. In so doing, we show that a formin isoform (i) is modified by posttranslational phosphorylation at serine and threonine residues and (ii) when present in a crude nuclear extract, is retained by DNA-cellulose.

3T3 Cells↗
PubMed1993

Taurine promotes the differentiation of a vertebrate retinal cell type in vitro.

The retina offers a model system for investigating the mechanisms that control cell type determination and differentiation in the vertebrate central nervous system. Previously, rod photoreceptor development in vitro was found to require a diffusible activity released by retinal cells (D. Altshuler and C. Cepko, Development 114, 947-957, 1992). In this report, we show that retinal-cell-conditioned medium and extracts contain two separable activities that influence rod development: a > 10 kDa inhibitory activity, and a stimulatory activity that is < 1 kDa and heat stable. Taurine was found to be a component of the < 1 kDa fraction and to stimulate rod development when added to retinal cultures. Taurine was not the only rod-promoting factor in these retinal preparations, however, as conditioned medium and extracts stimulated a higher level of rod development than did taurine alone. Taurine uptake into cells could be blocked without inhibiting taurine's ability to stimulate rod development, arguing against an osmoregulatory or nutritive mechanism of action. Finally, a competitive antagonist of taurine's bioactivity was identified and shown partially to inhibit rod development in retinal explants, suggesting that taurine may normally act to stimulate rod development in the retina. These results provide evidence for three activities, one of which is taurine, that are candidate regulators of rod photoreceptor development in vivo.

Animals↗
PubMed1992

The zickel nail in the treatment of metastatic bone disease in the upper end of the femur.

During a period of 5 years, 39 cases (37 patients) with metastatic bone disease in the proximal femur were treated by the insertion of a Zickel intramedullary nail using a 'closed' operative technique. The use of methyl methacrylate as an adjunct to fixation was not considered necessary. The results were satisfactory in terms of achieving stabilization of the fracture if present, relief of pain and the ability to commence early ambulation.

Adolescent↗
PubMed1991

A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine. RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued. CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Morbidity and mortality of patients with AIDS and first-episode Pneumocystis carinii pneumonia unaffected by concomitant pulmonary cytomegalovirus infection.

To determine the significance of cytomegalovirus (CMV) pulmonary coinfection with Pneumocystis carinii pneumonia in AIDS, we examined the association of long- and short-term survival and morbidity (as defined by length of hospital stay) with recovery of CMV from bronchoscopy specimens and an indirect measure of virus titer in bronchoalveolar lavage fluid (the time to develop CMV cytopathology in culture) in 111 patients diagnosed with a first episode of P. carinii pneumonia. Compared with 57 individuals from whom CMV was not isolated, the 54 individuals from whom CMV were isolated did not differ in baseline characteristics, long-term survival (213 versus 275 days, p = 0.97), acute death rate (19% in both, p = 1.0), or length of hospital stay (19.7 versus 21.1 days, p = 0.68). Also, the time to develop CMV cytopathology in culture did not correlate with acute or long-term survival. Our observations thus do not support the use of CMV-specific antiviral therapy in AIDS patients with P. carinii pneumonia who also have evidence of pulmonary CMV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

4-Aminopyridine in multiple sclerosis: prolonged administration.

In an earlier study, we demonstrated efficacy of single oral doses of 4-aminopyridine (4-AP) in improving motor and visual signs in multiple sclerosis (MS) patients for a mean of 4.97 hours. We attempted to determine whether efficacy could safely be prolonged using multiple daily doses over several days by administering 7.5 to 52.5 mg 4-AP to 17 temperature-sensitive MS patients in one to three daily doses at 3- to 4-hour intervals over 1 to 5 days in a double-blind study. Nine of these patients were also tested with identically appearing placebo. Thirteen of the 17 patients (76%) given 4-AP showed clinically important motor and visual improvements compared with three of nine in the placebo group. Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo. Seventy percent of the daily 4-AP improvements lasted 7 to 10 hours. The improvements for two consecutive doses of 4-AP lasted a mean of 7.07 hours (83% of the average 8.53-hour treatment-observation period) compared with 2.36 hours for placebo (26% of the average 9.06-hour treatment-observation period). No serious side effects occurred. 4-AP is a promising drug for the symptomatic treatment of MS.

4-Aminopyridine↗
PubMed1991

Chiari osteotomy in the adult: a long-term follow-up study.

For almost 20 years the Chiari pelvic displacement osteotomy has been used as a method of providing cover to the femoral head in cases of acetabular dysplasia. The osteotomy is one of a number of procedures that have been used in an attempt to prevent the early development of secondary osteo-arthritis and the need for total hip replacement. More recently, the operation has been undertaken in cases where there is already some arthritic change. This long-term review of 18 Chiari operations shows that the procedure was successful in cases of acetabular dysplasia where there was minimal subluxation of the femoral head (i.e. with Shenton's line still intact). In more advanced cases where there was significant subluxation (i.e. with Shenton's line broken by more than 1 mm) and even early arthritic changes, the results were poor. It is concluded that the operation may be of value as an almost 'prophylactic' procedure but that it is of no value as a so-called 'salvage' procedure.

Acetabulum↗
PubMed1990

Photoaffinity labeling of the Klenow fragment with 8-azido-dATP.

The photoaffinity compound 8-azido-dATP was used as a probe for the deoxyribonucleoside triphosphate-binding site of the large fragment of DNA polymerase I. Azido-dATP specifically modified a saturable binding site within the Klenow fragment, and each of the four natural deoxyribonucleoside triphosphate substrates competed with labeling at this site in proportion to its binding constant, as previously defined by equilibrium dialysis. Analysis of tryptic peptides after azido-dATP modification revealed five major cross-linking products, which apparently arose from five distinct photoadducts formed near Tyr-766.

Adenosine Triphosphate↗
PubMed1990

Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis.

4-Aminopyridine (4-AP), a potassium channel blocker, restores conduction in blocked, demyelinated animal nerve. Its administration to multiple sclerosis (MS) patients produces transient neurological improvements. Vision improves after either oral or intravenous administration, whereas motor function improvement has been reported only with the latter. To assess further its potential as a practical symptomatic treatment, we studied the efficacy of single, oral doses of 4-AP on both visual and motor signs in MS. Twenty temperature-sensitive male MS patients were given either 10 to 25 mg of 4-AP or identically appearing lactose placebo capsules. Static quantitative perimetry, critical flicker-fusion, visual acuity, visual evoked potentials, and videotaped neurological examinations were monitored. All of 15 MS patients given 4-AP mildly to markedly improved. Motor functions (power, coordination, gait) improved in 9 of 13 involved, vision in 11 of 13, and oculomotor functions in 1 of 2. Improvements developed gradually at doses as low as 10 mg, usually beginning within 60 minutes after drug administration, and reversed gradually over 4 to 7 hours. No serious adverse effects occurred. No significant changes were observed in 5 MS patients given placebo. We conclude that orally administered 4-AP produces clinically important improvements in multiple, chronic deficits in MS. Further studies are warranted to assess efficacy and safety of prolonged administration.

4-Aminopyridine↗
PubMed1990

A randomized controlled trial of a nursery ritual: wearing cover gowns to care for healthy newborns.

The routine wearing of individual cover gowns by nurses and visitors for direct care of healthy newborns was usual practice on the maternity ward of a regional referral center. We conducted a randomized trial in which cover gowns were not provided for care of infants in the experimental group (n = 222), but were maintained for control infants (n = 230). The principal outcome measured was Staphylococcus aureus colonization of the newborn nares or umbilicus on day 3 or day of discharge. Twenty percent (n = 51) of the experimental group (no gown) had a positive culture compared with 21 percent (n = 47) of the controls. Of the infants with positive cultures, two in each group exhibited symptoms of overt S. aureus infection. Experimental infants were similar to controls with respect to feeding method, route of delivery, amount of time spent rooming-in, and average number of visitors per day. In the group of positively cultured infants, the mothers experienced longer labor, and more vaginal examinations in labor, and the number of males undergoing circumcision was higher. We concluded that routine use of cover gowns was unwarranted, and we have altered the ward policy accordingly. This also has had a positive economic effect.

Ceremonial Behavior↗