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C J McDonald

Publications and source records attributed to C J McDonald.

At least 19 recordsLinked to original sources
PubMed1992

cDNA clones for mouse parotid proline-rich proteins. mRNA regulation by isoprenaline and the nucleotide sequence of proline-rich protein cDNA MP5.

cDNA clones for mRNA sequences regulated by isoprenaline in mouse parotid glands were identified by differential colony hybridisation and all hybridised to a diagnostic proline-rich protein (PRP) oligonucleotide. They were divided into two cross-hybridisation groups, A and B, which were shown by hybrid-selected translations to encode acidic PRP and basic PRP, respectively. The A-type subgroup consisted of sequences homologous to the previously identified mouse PRP genes MP2 and MP3. The B-type subgroup comprised clones for the previously identified cDNA pUMP125 (MP4) as well as other PRP sequences. Six of the B-type clones contained a novel PRP cDNA (MP5) and these were sequenced. The composite MP5 cDNA was 897 nucleotides long and contained an open reading frame capable of encoding a 260-residue-long salivary PRP precursor (30% Pro, 19% Gln and 18% Gly), containing nine variant repeat units of consensus PGNQQGPPPQGGPQQ(GPP)R(PPQ). MP5 was 80% identical to the sequence of MP4 and had a high degree of similarity (60%) at its 3'-untranslated region to rat salivary glutamate/glutamine-rich protein (GRP) cDNA. Two MP5 clones contained a 273-bp intron-like insertion in the 3' untranslated region, being derived, therefore, from incompletely spliced MP5 transcripts. Northern blotting showed that, although PRP mRNA species were induced by isoprenaline, a B-type PRP mRNA was present in normal parotid glands. RNA dot-blots probed with PRP-gene-specific oligonucleotides established that MP3, MP4 and MP5 PRP mRNA were all induced by isoprenaline.

Amino Acid Sequence↗
PubMed1992

Electron microscopic immunocytochemical localization of proline-rich proteins in normal mouse parotid salivary glands.

Rabbit polyclonal antibodies against isoproterenol-induced mouse proline-rich proteins (PRPs) were used to localize PRPs in the parotid salivary glands of normal adult BALB/c mice. The antibodies recognized both acidic-type and basic-type PRPs. Immunoblotting experiments revealed that the glands contained an acidic-type and a basic-type PRP. Parotid gland tissue was fixed with Karnosky's fixative and embedded in Lowicryl resin at low temperature. PRPs were localized at the electron microscope level using an indirect post-embedding staining technique with protein A-gold. The secretion granules of the acinar cells were strongly labelled. Pre-absorption of the antibody with purified acidic-type and basic-type PRPs indicated that the basic-type PRP is mainly located at the periphery of the granules but that the acidic-type PRP is more evenly distributed within the granules. Pre-absorption of the antibody with alpha-amylase did not affect the staining pattern, suggesting minimal cross-reactivity. PRPs were also detected within the rough endoplasmic reticulum and the Golgi apparatus of acinar cells, within the granules of the proacinar cells and in the lumena of the ducts, but not within the intercalated or striated duct cell granules.

Animals↗
PubMed1991

Gene sequence of mouse B-type proline-rich protein MP4. Transcriptional start point and an upstream phylogenetic footprint with ets-like and rel/NFkB-like elements.

A mouse genomic B-type proline-rich protein (PRP) cosmid clone was isolated by cDNA hybridisation and mapped, the gene region was subcloned and 3770 bp were sequenced. This gene (MP4) contained three introns and encoded a 1020-nt (nt, nucleotide) mRNA for a PRP precursor 300 amino acids long arranged with 11 imperfect 18-residue proline-rich repeats. The transcriptional start point was determined by S1 nuclease mapping and primer extension to be 26 bp downstream of a TATAA sequence. Sequence comparisons revealed that only two regions from positions -650 bp - -30 bp were highly conserved in all other PRP genes, PRP boxes 1 and 2. Box 1 at positions -112 to -135 contained ets-like and rel/NFkB-like elements and was 74% conserved over 23 bp. Box 2 at positions -33 - -51 was 53% conserved over 19 bp. A search of the EMBL and GenBank sequence libraries indicated that PRP box 1 was only present upstream of the known mammalian PRP gene sequences and was absent from other genes. These conserved sequences may thus be relevant to the tissue-specific and beta-adrenergic regulation of PRP gene transcription.

Amino Acid Sequence↗
PubMed1991

The mouse proline-rich protein MP6 promoter binds isoprenaline-inducible parotid nuclear proteins via a highly conserved NFkB/rel-like site.

Proline-rich protein (PRP) gene MP6 was isolated from a mouse BALB/c genomic DNA library in lambda EMBL3, characterised by hybridisation and restriction mapping and the promoter region, from -162 to +72 around the PRP consensus cap-site, was sequenced. In gel shift assays this region formed complexes C1 and C2 with parotid nuclear proteins which were induced by the beta-adrenergic agonist isoprenaline. DNA competition studies and direct binding assays of promoter subfragments showed that it was the sequence from -157 to -91 that was forming the isoprenaline-dependent complexes. All PRP genes conserve a 23bp. sequence, termed PRP Box1, with ets and NFkB/rel binding site-like elements, upstream of their promoters. In the MP6 promoter, PRP Box1 was within the region forming the complexes. Further gel shift assays using PRP Box1 oligonucleotides as competitors and targets indicated that the NFkB/rel binding site-like element was important in formation of the isoprenaline-inducible complexes. HeLa nuclear extracts also formed complexes with PRP Box1 similar to C1 and C2 but nuclear extracts from spleen, submandibular gland and liver did not. These complexes are thus candidate regulators for the isoprenaline-dependent and tissue-specific transcription of PRP genes.

Amino Acid Sequence↗
PubMed1991

Practice databases and their uses in clinical research.

A few large clinical information databases have been established within larger medical information systems. Although they are smaller than claims databases, these clinical databases offer several advantages: accurate and timely data, rich clinical detail, and continuous parameters (for example, vital signs and laboratory results). However, the nature of the data vary considerably, which affects the kinds of secondary analyses that can be performed. These databases have been used to investigate clinical epidemiology, risk assessment, post-marketing surveillance of drugs, practice variation, resource use, quality assurance, and decision analysis. In addition, practice databases can be used to identify subjects for prospective studies. Further methodologic developments are necessary to deal with the prevalent problems of missing data and various forms of bias if such databases are to grow and contribute valuable clinical information.

Clinical Medicine↗
PubMed1991

Beta-adrenergic regulation of beta-actin mRNA abundance in mouse parotid glands by a post-transcriptional mechanism.

In the first 24 h after a single injection of the beta-adrenergic agonist isoprenaline to mice, the level of beta-actin mRNA in the parotid glands increased significantly above that observed in untreated mice. The increase was transient, reaching 11 times the normal level 18 h after treatment and declining thereafter. Repeated daily doses of isoprenaline did not result in any further increase in beta-actin mRNA. Nuclear transcription experiments showed that there was no increase in the transcription rate of the beta-actin gene 8 h after an injection of isoprenaline, although beta-actin mRNA levels were increasing at this time. Immunoblotting revealed an increase in beta-actin protein in parotid gland samples after isoprenaline treatment, although the increase was not to the same extent as the mRNA, perhaps indicating that degradation of beta-actin had also increased. Using immunocytochemistry it was found that beta-actin was located mainly in the apical cortex of the normal acinar cell. There was a significant decrease in cortical beta-actin 24 h after isoprenaline treatment, suggesting that the beta-actin was under the process of redistribution. From these data we propose that isoprenaline caused an increase in beta-actin synthesis by a posttranscriptional mechanism and a redistribution of beta-actin in preparation for the well-known subsequent change in morphology and function of the parotid glands.

Actins↗
PubMed1991

Practice randomization and clinical research. The Indiana experience.

Thoughtful preparation of a research laboratory is an early step in designing a program for scientific investigation. The Division of General Internal Medicine at Indiana University has maintained a "laboratory" for outpatient clinical investigation for more than 15 years. In this report, we describe the structure and function of the General Medicine Practice in the Regenstrief Health Center on the campus of the Indiana University School of Medicine in Indianapolis. Specifically, we discuss the ongoing random allocation of subjects, the local resources for data management and tracking of patients' use of clinical services, and how combining this information system into a randomized primary care system has fostered successful ventures in clinical investigation.

Health Services Research↗
PubMed1990

The effect on test ordering of informing physicians of the charges for outpatient diagnostic tests.

We studied the effect of informing physicians of the charges for outpatient diagnostic tests on their ordering of such tests in an academic primary care medical practice. All tests were ordered at microcomputer workstations by 121 physicians. For half (the intervention group), the charge for the test being ordered and the total charge for tests for that patient on that day were displayed on the computer screen. The remaining physicians (control group) also used the computers but received no message about charges. The primary outcomes measured were the number of tests ordered and the charges for tests per patient visit. In the 14 weeks before the study, the number of tests ordered and the average charge for tests per patient visit were similar for the intervention and control groups. During the 26-week intervention period, the physicians in the intervention group ordered 14 percent fewer tests per patient visit than did those in the control group (P less than 0.005), and the charges for tests were 13 percent ($6.68 per visit) lower (P less than 0.05). The differences were greater for scheduled visits (17 percent fewer tests and 15 percent lower charges for the intervention group; P less than 0.01) than for unscheduled (urgent) visits (11 percent fewer tests and 10 percent lower charges; P greater than 0.3). During the 19 weeks after the intervention ended, the number of tests ordered by the physicians in the intervention group was only 7.7 percent lower than the number ordered by the physicians in the control group, and the charges for tests were only 3.5 percent lower (P greater than 0.3). Three measures of possible adverse outcomes--number of hospitalizations, emergency room visits, and outpatient visits during the study period and the following six months--were similar for the patients seen by the physicians in both groups. We conclude that displaying the charges for diagnostic tests significantly reduced the number and cost of tests ordered, especially for patients with scheduled visits. The effects of this intervention did not persist after it was discontinued.

Ambulatory Care↗
PubMed1990

Ibuprofen-associated renal impairment in a large general internal medicine practice.

The authors determined the incidence of ibuprofen-associated renal impairment and risk factors for its development in 1908 patients treated with ibuprofen using data from a computerized medical records system. Renal impairment occurred in 343 patients (18%). Multivariable analysis revealed six independent predictors of renal impairment: age, prior renal insufficiency, coronary artery disease, male gender, elevated systolic blood pressure, and diuretic use. They then tested the degree to which ibuprofen contributed to the development of renal impairment by evaluating a control group of 3933 acetaminophen recipients. Neither ibuprofen nor acetaminophen was among the independent predictors of risk when all patients were considered (adjusted odds ratio, 1.05; 95% Cl, 0.88-1.26). However, two subsets of at risk patients had an ibuprofen effect: patients greater than or equal to 65 years of age who received ibuprofen were at greater risk of renal impairment as compared to acetaminophen recipients (adjusted odds ratio, 1.34; 95% Cl, 1.05 to 1.72) as were patients with coronary artery disease (adjusted odds ratio, 2.54; 95% Cl, 1.38 to 4.68). Their results suggest that elderly patients and patients with coronary artery disease are at risk for ibuprofen-associated renal impairment and therefore should have their renal function monitored when ibuprofen and possibly other nonsteroidal anti-inflammatory drugs are prescribed.

Acetaminophen↗
PubMed1979

Immunosuppressive therapy in collagen vascular diseases.

Over the past ten to fifteen years cytotoxic drugs have gradually been added to the therapeutic armamentarium of physicians other than oncologists, particularly dermatologists. They are being used to treat nonmalignant cutaneous diseases such as pemphigus vulgaris, bullous pemphigoid, and psoriasis. The rationale for their use in these diseases is conjectural, yet those dermatologists who use them feel strongly not only that cytotoxic drugs are effective, but that when used properly, they are relatively safe. The immunosuppressive activity of cytotoxic drugs has been accepted and widely acclaimed in immunology, renology, and transplant medicine. However, their usefulness in two autoimmune diseases frequently managed by dermatologists is widely disputed. In this short discussion the rationale for the use of cytotoxic agents and evidence for their effectiveness when used appropriately in progressive systemic sclerosis and systemic lupus erythematosus is presented.

Antibody Formation↗
PubMed1978

Psoriasis and occlusive vascular disease.

To test the hypothesis that psoriasis is associated with an increased incidence of occlusive vascular disease (thrombophlebitis, myocardial infarction, pulmonary embolization, and cerebrovascular accident), the clinical records of 323 psoriatic and 325 non-psoriatic patients admitted to the dermatology service of the Roger Williams General Hospital were examined. The data obtained in this study suggest that (1) the occurrence rate of occlusive vascular disease is significantly greater in the psoriatic than in the non-psoriatic dermatological patient. This is particularly true in the male population; (2) psoriasis predisposes to occlusive vascular disease; and (3) the psoriatic patient with certain predisposing factors is at greater risk of experiencing an occlusive vascular episode than both the non-predisposed psoriatic and the non-psoriatic dermatological patient.

Age Factors↗
PubMed1978

Mycophenolic acid in psoriasis.

Mycophenolic acid (MPA) is a fermentation product of a penicillium mould which has shown antitumour acitivity in certain animal models. It blocks nucleic acid synthesis by interfering with the interconversions of inosine monophosphate (IMP), xanthine monophosphate (XMP) and guanine monophosphate (GMP) thereby inhibiting growth and/or replication of tumour cells. In vivo activity depends on the presence of a beta-glucuronidase which is abundant in the cell wall of epithelial tissues. Encouraged by results obtained in earlier clinical trials, we have studied 28 patients with psoriasis, 21 in double-blind fashion. A comparison of disease severity in patients before and after receiving MPA versus patients receiving placebo clearly showed the superiority of drug over placebo. The mean severity score of patients receiving MPA as an initial course of therapy improved by 56% versus 9% in patients receiving placebo. Patients receiving MPA after an initial course of placebo therapy showed improvement in their mean severity score averaging 86%. Those patients receiving placebo after an initial course of MPA showed worsening of their mean severity score averaging 70%. Overall, about 75% of MPA treated patients have shown good to excellent responses, and toxicity appears low. Evidence suggests that MPA may be very useful in treating severe psoriasis.

Adult↗