PubMed Health⌕ Search

Biomedical subjects

J L Newman

Publications and source records attributed to J L Newman.

At least 19 recordsLinked to original sources
PubMed2001

Structure-activity relationship studies of 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine derivatives and their N-analogues: evaluation of O-and N-analogues and their binding to monoamine transporters.

In our effort to develop a pharmacotherapy for the treatment of cocaine addiction, we embarked on synthesizing novel molecules targeting the dopamine transporter (DAT) molecule in the brain as DAT has been implicated strongly in the reinforcing effect of cocaine. Our previously developed DAT-selective piperidine analogue, 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, was the basis for our current structure-activity relationship (SAR) studies exploring the significance of the contribution of the benzhydryl O- and N-atoms in these molecules in interacting with the DAT. Thus, we replaced the benzhydryl O-atom with an N-atom, altered the location of the benzhydryl N-atom to an adjacent position, and in one other occasion converted the benzhydryl O-ether linkage into an oxime-type derivative. Furthermore, we also evaluated the important contribution of the piperidine N-atom to binding by altering its pK(a) value chemically. Novel analogues were tested for potency in inhibiting [3H]WIN 35,428, [3H]citalopram, and [3H]nisoxetine binding at the DAT, serotonin transporter (SERT), and norepinepherine transporter (NET). [3H]DA was used to measure DA reuptake inhibition. The results indicated that the benzhydryl O- and N-atoms are exchangeable for the most part. On the other hand, an enhanced interaction with the SERT was observed when the benzhydryl N-atom moved to an adjacent position (21a; DAT (IC(50)) = 19.7, SERT (IC(50)) = 137 nM, NET (IC(50)) = 1111 nM). In either cases, further alkylation of the N-atom reduced the activity for the transporter. The presence of a powerful electron-withdrawing cyano group in compound 5d expectedly produced the most potent and selective ligand for the DAT (DAT (IC(50)) = 3.7 nM, DAT/SERT = 615). Selected compounds were further analyzed in the dopamine reuptake inhibition assay. Preliminary behavioral assessment of some of the selected compounds in mice indicated that these compounds are much less stimulating when compared with cocaine at comparable doses. In drug-discrimination studies these selected compounds incompletely generalized from the cocaine stimulus in mice trained to discriminate 10 mg/kg cocaine from vehicle.

Animals↗
PubMed2000

Solution structure and dynamics of the Rous sarcoma virus capsid protein and comparison with capsid proteins of other retroviruses.

The solution structure and dynamics of the recombinant 240 amino acid residue capsid protein from the Rous sarcoma virus has been determined by NMR methods. The structure was determined using 2200 distance restraints and 330 torsion angle restraints, and the dynamics analysis was based on (15)N relaxation parameters (R(1), R(2), and (1)H-(15)N NOE) measured for 153 backbone amide groups. The monomeric protein consists of independently folded N- and C-terminal domains that comprise residues Leu14-Leu146 and Ala150-Gln226, respectively. The domains exhibit different rotational correlation times (16.6(+/-0.1) ns and 12.6(+/-0.1) ns, respectively), are connected by a flexible linker (Ala147-Pro149), and do not give rise to inter-domain NOE values, indicating that they are dynamically independent. Despite limited sequence similarity, the structure of the Rous sarcoma virus capsid protein is similar to the structures determined recently for the capsid proteins of retroviruses belonging to the lentivirus and human T-cell leukemia virus/bovine leukemia virus genera. Structural differences that exist in the C-terminal domain of Rous sarcoma virus capsid relative to the other capsid proteins appear to be related to the occurrence of conserved cysteine residues. Whereas most genera of retroviruses contain a pair of conserved and essential cysteine residues in the C-terminal domain that appear to function by forming an intramolecular disulfide bond during assembly, the Rous sarcoma virus capsid protein does not. Instead, the Rous sarcoma virus capsid protein contains a single cysteine residue that appears to be conserved among the avian C-type retroviruses and is positioned in a manner that might allow the formation of an intermolecular disulfide bond during capsid assembly.

Amino Acid Sequence↗
PubMed2000

Survey of the fragile X syndrome CGG repeat and the short-tandem-repeat and single-nucleotide-polymorphism haplotypes in an African American population.

Previous studies have shown that specific short-tandem-repeat (STR) and single-nucleotide-polymorphism (SNP)-based haplotypes within and among unaffected and fragile X white populations are found to be associated with specific CGG-repeat patterns. It has been hypothesized that these associations result from different mutational mechanisms, possibly influenced by the CGG structure and/or cis-acting factors. Alternatively, haplotype associations may result from the long mutational history of increasing instability. To understand the basis of the mutational process, we examined the CGG-repeat size, three flanking STR markers (DXS548-FRAXAC1-FRAXAC2), and one SNP (ATL1) spanning 150 kb around the CGG repeat in unaffected (n=637) and fragile X (n=63) African American populations and compared them with unaffected (n=721) and fragile X (n=102) white populations. Several important differences were found between the two ethnic groups. First, in contrast to that seen in the white population, no associations were observed among the African American intermediate or "predisposed" alleles (41-60 repeats). Second, two previously undescribed haplotypes accounted for the majority of the African American fragile X population. Third, a putative "protective" haplotype was not found among African Americans, whereas it was found among whites. Fourth, in contrast to that seen in whites, the SNP ATL1 was in linkage equilibrium among African Americans, and it did not add new information to the STR haplotypes. These data indicate that the STR- and SNP-based haplotype associations identified in whites probably reflect the mutational history of the expansion, rather than a mutational mechanism or pathway.

Black or African American↗
PubMed2000

Triclosan: a review of effectiveness and safety in health care settings.

Triclosan is a widely accepted antimicrobial ingredient because of its safety and antimicrobial efficacy. Triclosan is a unique antimicrobial well suited for use in the health care industry in which mildness is a necessity to protect the health care worker during repeated use and antimicrobial activity is a necessity to protect public health. Triclosan has demonstrated immediate, persistent, broad-spectrum antimicrobial effectiveness and utility in clinical health care settings. This review highlights the utility and effectiveness of a 1% triclosan formulation for use in high-risk, high-frequency handwashing.

Anti-Infective Agents, Local↗
PubMed1999

Ureteral rhabdomyosarcoma.

Rhabdomyosarcoma is a malignant tumor well known to urologists. These tumors arise from the genitourinary system in 20% to 25% of cases, most commonly from the bladder, prostate, vagina, and paratesticular region. This is the first reported case of a rhabdomyosarcoma arising from the ureter. The radiographic findings and ureteroscopic appearance of this tumor suggested a benign fibroepithelial polyp; however, a ureteroscopic biopsy and subsequent nephroureterectomy revealed an embryonal rhabdomyosarcoma.

Adult↗
PubMed1999

Prevalence and phenotype consequence of FRAXA and FRAXE alleles in a large, ethnically diverse, special education-needs population.

We conducted a large population-based survey of fragile X (FRAXA) syndrome in ethnically diverse metropolitan Atlanta. The eligible study population consisted of public school children, aged 7-10 years, in special education-needs (SEN) classes. The purpose of the study was to estimate the prevalence among whites and, for the first time, African Americans, among a non-clinically referred population. At present, 5 males with FRAXA syndrome (4 whites and 1 African American), among 1,979 tested males, and no females, among 872 tested females, were identified. All males with FRAXA syndrome were mentally retarded and had been diagnosed previously. The prevalence for FRAXA syndrome was estimated to be 1/3,460 (confidence interval [CI] 1/7,143-1/1,742) for the general white male population and 1/4, 048 (CI 1/16,260-1/1,244) for the general African American male population. We also compared the frequency of intermediate and premutation FRAXA alleles (41-199 repeats) and fragile XE syndrome alleles (31-199 repeats) in the SEN population with that in a control population, to determine if there was a possible phenotype consequence of such high-repeat alleles, as has been reported previously. No difference was observed between our case and control populations, and no difference was observed between populations when the probands were grouped by a rough estimate of IQ based on class placement. These results suggest that there is no phenotype consequence of larger alleles that would cause carriers to be placed in an SEN class.

Alleles↗
PubMed1991

Cryptosporidium infection in acquired immunodeficiency syndrome: not always a poor prognosis.

Chronic diarrhea and malabsorption accompanied by simultaneous infection with the protozoa Giardia lamblia and Cryptosporidium occurred in a 22-year-old homosexual man with antibody to human immunodeficiency virus (HIV). Small bowel biopsy demonstrated total villous atrophy and marked mononuclear infiltration in the lamina propria simulating celiac disease. Treatment with metronidazole resulted in resolution of diarrhea, clearance of parasites, and marked improvement in small bowel histology. Although diarrhea and malabsorption in immunocompromised patients with cryptosporidiosis are regarded as ominous, our patient remained disease free for the next 3 years. Thus, infection with Cryptosporidium in patients with HIV does not always lead to intractable diarrhea or death.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Intermittent use of an antimicrobial hand gel for reducing soap-induced irritation of health care personnel.

We evaluated the effects of an antimicrobial hand gel (containing 60% ethanol plus emollients) on skin condition when used as a supplement to handwashing. Volunteers washed their hands 10 times per day for 5 days with a bar soap. Between washings one hand was treated with 1.0 ml of the gel while the other hand was untreated. By the conclusion of the study the gel-treated hands exhibited significantly lower (p less than 0.05) photographic scores for cracking, scaling, and erythema (redness), the major symptoms of dry, irritated skin. The gel treatment also helped to maintain normal skin hydration levels as measured by transepidermal water loss and skin impedance. By reducing soap-induced irritation, an alcohol gel with the appropriate emollients can help eliminate a major deterrent to handwashing among health care personnel.

Adult↗
PubMed1988

Factors affecting skin condition in two nursing populations: implications for current handwashing protocols.

Two different nursing populations--one from Phoenix, Arizona, and the other from Racine, Wisconsin--and a group of persons prone to dry skin from Racine were evaluated for the presence of scaling, cracking, and erythema, the major visible symptoms of hands with dry, chapped skin. The results provide insight into the effects of age, season, geographic locale, handwashing frequency, and work area on skin condition. Season (winter), geographic locale (northern locale), and age (over 30 years) were the most significant extrinsic factors influencing the manifestation of hands with dry, chapped skin. In the presence of these predisposing factors, a handwashing frequency of only one to two times per hour was sufficient to significantly increase the severity of dry skin. Among nurses those most susceptible to dry skin were over 30 years of age, were high-frequency (more than three washings per hour) hand washers, and were exposed to the winter climate of a northern locale.

Adult↗
PubMed1986

Phase behavior of synthetic N-acylethanolamine phospholipids.

Both saturated and unsaturated N-acylethanolamine phospholipids form lamellar structures when dispersed in buffer. The addition of excess Ca2+ (Ca2+/N-acylphosphatidylethanolamine greater than 0.5) results in precipitation. Freeze-fracture replicas indicate that the addition of Ca2+ to the unsaturated lipid results in a non-bilayer structure while the Ca2+-complex of the saturated lipid is lamellar. Since unsaturated phosphatidylethanolamine (PE) is a non-bilayer lipid, its N-acylation with a saturated fatty acid converts a non-bilayer lipid into an acidic bilayer lipid capable of interacting with Ca2+ to return to a non-bilayer structure. Ca2+ may thereby exert an influence on membrane phenomena by regulating phase behavior within certain membrane domains. Differential scanning calorimetry (DSC) indicates that N-acylation of unsaturated PE with a saturated fatty acid also results in changes in thermotropic phase behavior. Therefore, N-acylation may affect fluidity within certain membrane domains.

Calcium↗
PubMed1985

Unequal homologous recombination between tandemly arranged sequences stably incorporated into cultured rat cells.

Cultured rat cells deficient in endogenous thymidine kinase activity (tk) were stably transformed with a recombination-indicator DNA substrate constructed in vitro by rearrangement of the herpes simplex virus tk gene sequences into a partially redundant permutation of the functional gene. The recombination-indicator DNA did not express tk, but was designed to allow formation of a functional tk gene via homologous recombination. A clonal cell line (519) was isolated that harbored several permuted herpes simplex virus tk genes. 519 cells spontaneously produced progeny that survived in medium containing hypoxanthine, aminopterin, and thymidine. Acquisition of resistance to hypoxanthine, aminopterin, and thymidine was accompanied by the rearrangement of the defective tk gene to functional configuration. The rearrangement apparently occurred by unequal exchange between one permuted tk gene and a replicated copy of itself. Recombination was between 500-base-pair tracts of DNA sequence homology that were separated by 3.4 kilobases. Exchanges occurred spontaneously at a frequency of approximately 5 X 10(-6) events per cell per generation. Recombination also mediated reversion to the tk- phenotype; however, the predominant mechanism by which cells escaped death in the presence of drugs rendered toxic by thymidine kinase was not recombination, but rather inactivation of the intact tk gene.

Animals↗