Biomedical subjects

A J Newman

Publications and source records attributed to A J Newman.

At least 37 records · Page 2Linked to original sources

PubMed1993

Alprazolam and depression: a review of risks and benefits.

Therapeutic efficacy for depression and panic disorder has been demonstrated with the triazolobenzodiazepine alprazolam. However, potentially serious adverse events, including depression and suicide attempts, have been reported in patients taking this medication. In this paper, reports addressing the association between each of these two events and benzodiazepine use in general and, more specifically, alprazolam use, are reviewed. We conclude that while these adverse events do occur in patients taking alprazolam, the causal relationship remains unclear and requires further study. Fortunately, these events are observed only rarely, so the prudent clinician may continue to safely prescribe this useful medication.

Adolescent↗

PubMed1992

Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group.

BACKGROUND: The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials. METHODS: Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed. RESULTS: The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity. CONCLUSIONS: Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.

Administration, Oral↗

PubMed1992

U5 snRNA interacts with exon sequences at 5' and 3' splice sites.

U5 snRNA is an essential pre-mRNA splicing factor whose function remains enigmatic. Specific mutations in a conserved single-stranded loop sequence in yeast U5 snRNA can activate cleavage of G1----A mutant pre-mRNAs at aberrant 5' splice sites and facilitate processing of dead-end lariat intermediates to mRNA. Activation of aberrant 5' cleavage sites involves base pairing between U5 snRNA and nucleotides upstream of the cleavage site. Processing of dead-end lariat intermediates to mRNA correlates with base pairing between U5 and the first two bases in exon 2. The loop sequence in U5 snRNA may therefore by intimately involved in the transesterification reactions at 5' and 3' splice sites. This pattern of interactions is strikingly reminiscent of exon recognition events in group II self-splicing introns and is consistent with the notion that U5 snRNA may be related to a specific functional domain from a group II-like self-splicing ancestral intron.

Base Sequence↗

PubMed1992

Sarcoidosis associated with nephrocalcinosis in young children.

Three patients with nonpulmonary sarcoidosis had chronic erythema nodosum within the first 2 years of life. Each subsequently had renal sarcoidosis and nephrocalcinosis; hypercalcemia was documented in each patient and hypercalciuria in two patients. Treatment with prednisone was not uniformly successful in normalizing creatinine clearance. Nephrocalcinosis may be more common than previously reported in patients with sarcoidosis.

Biopsy↗

PubMed1989

Evidence that introns arose at proto-splice sites.

The unexpected discovery of introns raised many questions about gene evolution. We provide evidence that actin and tubulin introns were gained between the G and R of the conserved coding sequence C/AAGR that is known to flank introns in general and which we call a proto-splice site. We conclude that the tubulin and actin introns are less ancient than the coding sequence and so could not have been involved in the primary evolution of the tubulin and actin genes.

Actins↗

PubMed1988

Poststeroid panniculitis: a case report.

Firm, red, subcutaneous plaques developed on the cheeks of a 19-month-old girl during a one-month period of rapid steroid withdrawal. The clinical features were most consistent with poststeroid panniculitis. This rare complication of steroid therapy should be differentiated from other causes of red cheeks in children.

Diagnosis, Differential↗

PubMed1988

Magnetic resonance imaging of ruptured Baker's cyst.

The clinical presentation of a ruptured Baker's cyst and of thrombophlebitis can be identical. Venography, arthrography, and more recently ultrasonography have been used to differentiate these two entities. We report a patient with a ruptured Baker's cyst who was also evaluated using magnetic resonance imaging (MRI). The soft-tissue abnormalities were better demonstrated by MRI than by the other imaging methods.

Adolescent↗

PubMed1987

Assessment of the reliability and validity of the arthritis impact measurement scales for children with juvenile arthritis.

There are few multidimensional measures of functional status in children, and none have been developed for children with juvenile arthritis (JA). This report describes an attempt to apply selected components of the Arthritis Impact Measurement Scales (AIMS), which were developed and validated for adults, to a sample of children with active JA (n = 60) or inactive JA (n = 17). Our results suggest that the Pain scale and the Physical Activity scale are the most reliable measures for children with JA; the correlations of the Pain scale, Physical Activity scale, and Dexterity scale results with the clinical measures of JA diagnostic category and joint count support the convergent validity of these scales for the active JA group; and the AIMS revised Physical Disability dimension and the Pain dimension, used to predict the children's classification in the active or inactive JA group, evidence discriminant validity. Additional studies of children with a wider range of impairments are needed to further assess the usefulness of the AIMS for children with JA.

Arthritis, Juvenile↗

PubMed1987

Juvenile rheumatoid arthritis: assessment with MR imaging.

Thirty-three joints of the appendicular skeleton in 15 children with juvenile rheumatoid arthritis were examined with magnetic resonance (MR) imaging to determine if it could demonstrate synovial hypertrophy and status of the articular cartilage. Presumed synovial hypertrophy was seen in 13 joints as masses of varying sizes of low to intermediate signal intensity on T1- and T2-weighted images; sometimes foci of increased signal intensity, most likely due to fluid or inflammation, were seen on T2-weighted images. Probable abnormal articular cartilage was detected in ten joints, and MR imaging also demonstrated epiphyseal overgrowth, bone erosions, joint effusions, and joint space narrowing. Because MR imaging appears to provide an objective method of evaluating both synovial hypertrophy and status of articular cartilage, it may prove to be useful in monitoring progression of juvenile rheumatoid arthritis and response to therapy.

Adolescent↗

PubMed1986

Tumor-producing and skin-irritating activity of dithranol (anthralin) and its 10-acyl analogues in SENCAR mice.

The tumor-producing and skin-irritating activity of the antipsoriatic drug dithranol and its 10-acyl analogues butantrone (10-butyryl dithranol), 10-isobutyryl dithranol and 10-valeryl dithranol were studied in 650 SENCAR mice using a two-stage skin carcinogenesis assay. An initiation with 20 micrograms of 7,12-dimethylbenz(alpha)anthracene (DMBA) was followed 2 weeks later by three applications per week of the test compounds in 50 microliter of acetone for 21 weeks. In addition the compounds were studied without DMBA pre-treatment using application periods of 21 and 36 weeks. The concentration of dithranol was the maximum tolerated, 3.5 mM. For the less irritating 10-acyl analogues 30 mM solutions were used. The first signs of skin irritation were observed after an application period of 1-2 weeks and the irritation continued to the end of the experiment in all groups except the acetone controls. Dithranol caused the most severe irritation although the differences between the groups were not pronounced. On histopathology, the majority of animals had hyperplasia and other inflammatory changes of the skin. The first papillomas appeared 8-11 weeks after initiation and the incidences of papillomas at the end of the experiment were 85% (dithranol 3.5 mM), 16% (butantrone 30 mM), 36% (10-isobutyryl dithranol 30 mM) and 50% (10-valeryl dithranol 30 mM). Without initiation the incidences were 6 and 2% (dithranol), 2 and 2% (butantrone) and 2 and 0% (10-valeryl dithranol) in the 21- and 36-week studies, respectively. Histologically, the papillomas were mostly squamous papillomas and only a few keratoacanthomas were found. It is concluded that the tumor-producing and skin-irritating activity of dithranol is clearly greater than that of butantrone, 10-isobutyryl dithranol and 10-valeryl dithranol.

Animals↗

PubMed1985

Yeast mRNA splicing in vitro.

Synthetic actin and CYH2 pre-mRNAs containing a single intron are accurately spliced in a soluble whole cell extract of yeast. Splicing in vitro requires ATP. The excised intron is released as a lariat in which an RNA branch connects the 5' end of the molecule to the last A in the "intron conserved sequence" UACUAAC. Two other discrete RNA species produced during splicing in vitro may represent reaction intermediates: free, linear exon 1 and a form of the intron lariat extending beyond the 3' splice site to include exon 2. Both lariat forms correspond to molecules previously shown to be produced during yeast pre-mRNA splicing in vivo.

Actins↗

PubMed1985

Molecular consequences of specific intron mutations on yeast mRNA splicing in vivo and in vitro.

We have altered the TACTAAC sequence in the yeast CYH2m gene intron to TACTACC. This mutation changes the nucleotide at the normal position of the branch in intron RNA lariats produced during pre-mRNA splicing, and it prevents splicing in vivo. In a yeast pre-mRNA splicing system, CYH2m pre-mRNA carrying the TACTACC mutation is not specifically cut or rearranged in any way. Substitution of an A for the first G of the CYH2m intron, converting the highly conserved GTATGT 5' splice site sequence to ATATGT, also blocks intron excision in vivo and in vitro: pre-mRNA carrying this mutation was still cut normally at the mutant 5' splice site in vitro, to give authentic exon 1 and an intron-exon 2 lariat RNA with an A-A 2'-5' phosphodiester linkage at the branch point. This lariat RNA is a dead-end product. The subsequent cleavage at the 3' splice site is therefore sensitive to the sequence of the 5' end of the intron attached at the branch point.

Base Sequence↗

PubMed1985

Multifocal osteonecrosis in adolescents with Crohn's disease: a complication of therapy?

Three adolescents with severe Crohn's ileocolitis developed osteonecrosis after receiving intravenous corticosteroids and parenteral nutrition, including 10% lipid infusion. Each had achieved clinical remission with therapy. However, several months following completion of therapy, each developed arthralgias and arthritis of weight-bearing and non-weight-bearing joints. Roentgenographic evaluation revealed osteonecrosis involving multiple joints. Osteonecrosis may result from the interference with blood flow to bone and has been produced in animals by infusion of lipid solutions and administration of corticosteroids. We report these cases of osteonecrosis as a probable complication of corticosteroid and lipid infusion in adolescents treated for severe Crohn's disease.

Adolescent↗

PubMed1985

Psychogenic purpura in adolescent patients.

The occurrence of psychogenic purpura has been documented in adults. The authors present their experience with nine adolescent and young adult patients observed since 1981. The age of eight of these patients ranged from 13 to 18 years. One patient with cystic fibrosis was 23-years-old. All patients presented with painful inflammatory lesions followed by bruising. There was no evidence of an infectious process or a hematologic, immunologic, or renal abnormality. Integral to the diagnosis was the existence of an underlying emotional disorder. In all patients, bruising decreased after diagnosis was explained to the patient and family. Four patients required psychotherapy. Results of 2-year follow-up suggest that early intervention may produce a favorable outcome in this age group.

Adolescent↗

PubMed1984

Impairment of urate excretion in patients with cardiac disease.

The serum uric acid levels and uric acid clearance rates were evaluated in 28 patients who had congenital heart disease. Based on hemodynamic assessments, the patients were divided into three groups: group 1, with normal cardiac output and normal arterial oxygen saturation; group 2, with hypoxemia (normal cardiac output with a decreased arterial oxygen saturation); and group 3, with cardiomyopathy (decreased cardiac output). The blood levels of uric acid were elevated in group 3. The mean serum uric acid levels were as follows: group 1, 4.2 mg/dL; group 2, 4.8 mg/dL; and group 3, 11.7 mg/dL. All the patients in groups 2 and 3 had decreased uric acid clearance rates. The mean uric acid clearance rates were as follows: group 1, 10.1 mL/min/sq m; group 2, 4.2 mL/min/sq m; and group 3, 1.7 mL/min/sq m. The patients in group 3 had the most severe abnormalities. Patients with congenital heart disease may have marked impairment of their uric acid excretion, which can occur in the absence of significant renal disease, and may be found in acyanotic as well as cyanotic patients.

Adolescent↗

PubMed1983

tRNA gene transcription in yeast: effects of specified base substitutions in the intragenic promoter.

The yeast SUP53 gene encodes a leucine-inserting amber suppressor tRNA. We have introduced specific base substitutions into both 5' and 3' elements of the intragenic promoter of this tRNA gene. The influence of these sequence changes on promoter function has been investigated by transcription of the mutant genes in a homologous cell-free system. Our results do not support the idea that tertiary intragenic structure is important in tRNA gene transcription. For one of the SUP53 mutants we are able to suggest a plausible molecular basis for defective transcription: a single base substitution in the 3' element of the intragenic promoter prevents the interaction of this element with a putative transcription factor.

Base Composition↗

PubMed1982

Evidence that rifampicin can stimulate readthrough of transcriptional terminators in Escherichia coli, including the attenuator of the rpoBC operon.

The genes encoding the beta and beta' subunits of RNA polymerase in E.coli, rpoB and rpoC, lie downstream of at least two ribosomal protein genes, rplJ (encoding L10) and rplL (L7/12), in a common operon. All four genes are served by promoter PL10, and an attenuator (partial terminator) of transcription, t1, lies between rplJL and rpoBC. Treatment of E.coli with rifampicin, under conditions producing partial inhibition of general RNA synthesis, can stimulate transcription of rpoBC. We have investigated the locus of this effect by fusing PL10 and t1 separately to galK, in suitable plasmids. Our studies of these fusions, and similar fusions involving transcriptional terminators derived from coliphage T7, indicate that low concentrations of rifampicin cause increased readthrough of several different transcriptional terminators in E.coli in vivo, including rpo t1. We discuss whether or not this unspecific mechanism is solely responsible for the observed stimulatory effects of the drug on rpoBC transcription.

Base Sequence↗

PubMed1982

Effect of rifampicin on expression of lacZ fused to promoters or terminators of the E.coli rpoBC operon.

The genes encoding the beta and beta' subunits of RNA polymerase in E.coli lie downstream of at least two ribosomal protein genes in a single unit of transcription. Treatment of E.coli with rifampicin, under conditions producing partial inhibition of general RNA synthesis, can strongly stimulate transcription of the polymerase genes, while activating the neighbouring ribosomal genes only slightly. We have investigated the mechanism of this effect by fusing strong promoters, a weak internal promoter, and an attenuator of the polymerase operon to the lacZ gene, in derivatives of plasmid pMC81. Studies of these fusions confirm our conclusion, based on similar fusions to galK, that rifampicin can foster readthrough of transcriptional terminators. They also suggest the existence of extra terminators and anti-termination elements in the above transcription unit.

DNA Restriction Enzymes↗