PubMed Health⌕ Search

Biomedical subjects

R Holmes

Publications and source records attributed to R Holmes.

At least 19 recordsLinked to original sources
PubMed1992

Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression.

Recently we reported that, in HL-60 cells, transcription of the formyl peptide receptor (FPR) gene can be up- and downregulated by agents that induce differentiation of HL-60 cells into neutrophils. To begin studying the mechanisms involved in regulation of FPR gene expression, we cloned two human cDNAs and the gene coding for FPR. The genomic clone (pINF14) contained a 14.5-kb insert. A 2.7-kb EcoRI fragment was obtained from pINF14 that hybridized with an FPR open reading frame probe. The EcoRI fragment was sequenced and found to contain an intronless FPR open reading frame. Sequence alignment of the EcoRI genomic fragment with the FPR cDNA revealed that the first 31 bases of 5' untranslated FPR cDNA were not represented in the genomic fragment. Furthermore, a splicing consensus sequence was present in the genomic fragment at the site of divergence with the cDNA sequence. Restriction mapping and Southern blot analysis identified a 121-bp fragment that contained the sequence corresponding to the first 31 bases of 5' untranslated FPR cDNA. An additional (previously undescribed) 15-bp cDNA sequence in the 5' end of FPR were identified using an anchored polymerase chain reaction. This sequence was also contained in the genomic 121-bp fragment. This 121-bp fragment was located 5.2 kb (intron) upstream of the FPR open reading frame. It contained an unusual TATA box and displayed transcriptional activity in vitro and in vivo. Potential binding sites for AP-1 and glucocorticoid receptor were identified upstream of the putative TATA box.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils.

We cloned a cDNA (RFP) encoding a receptor (RFP) related (70% overall nucleotide homology) to the formyl peptide receptor of human neutrophils (hFPR). RFP is a seven-transmembrane-domain receptor and its distribution is limited to myeloid cells. Domain sequence comparison with hFPR reveals highly conserved regions and provides clues to putative domains involved in ligand binding and receptor desensitization.

Amino Acid Sequence↗
PubMed1992

Regulation of formyl peptide receptor expression and its mRNA levels during differentiation of HL-60 cells.

When incubated with N6-2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP), HL-60 cells expressed formyl peptide receptor (FPR) (as assessed by ligand binding) and FPR transcripts in a time- and concentration-dependent fashion. Experiments using dbcAMP analogs modified at either the C-6 or C-8 position indicated that the process was mediated by a protein kinase A type I, and protein kinase A type I activity was isolated from undifferentiated HL-60 cells by DEAE-Sephacel chromatography. Forskolin mimicked the effects of dbcAMP. Forskolin and dbcAMP-dependent expression of FPR and FPR transcript was inhibited by staurosporine. Retinoic acid (but not retinal or retinol) was capable of inhibiting dbcAMP-dependent expression of FPR mRNA half-life. Dexamethasone enhanced the effects of dbcAMP and blocked the inhibitory effect of retinoic acid on expression of FPR and FPR transcripts. Phorbol 12-myristate 13-acetate (PMA) alone (1.5-15 nM) failed to induce HL-60 to express FPR and FPR transcripts. Low concentrations (1.5 nM) of PMA enhanced the ability of dbcAMP to induce HL-60 cells to express FPR and FPR transcript, whereas high (15 nM) concentrations of PMA inhibited dbcAMP effects. These results indicate that expression of FPR and FPR transcripts by HL-60 cells can be up- and down-regulated by agents that induce HL-60 cells to differentiate and that a "cross-talk" effect exists between protein kinase A and protein kinase C that modulates FPR gene transcription (and receptor expression) by these cells.

Alkaloids↗
PubMed1992

Development of aldehyde dehydrogenase and alcohol dehydrogenase in mouse eye: evidence for light-induced changes.

We have studied the development of ocular aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) activities in C57BL/6J inbred male mice. Eyes were removed from freshly killed mice, enucleated, extracted, and analyzed for enzyme activities for animals of various ages during neonatal development, up to the adult stage. Activity levels were compared between mice maintained from birth in either complete darkness or on a 12-hour light/dark cycle. Ocular ALDH activity increased dramatically (greater than 30-fold) during the first 3 weeks of life. Moreover, light-adapted animals showed significantly higher ALDH activities from day 8. Ocular ADH activity also increased during development (greater than 5-fold) although the profile showed a steady increase to reach adult levels. Light-adapted mice showed no significant differences in ADH activity up to the weaning stage, as compared with mice maintained in darkness. These observations support proposals from earlier studies for major functional roles for both corneal ALDH and ADH in protecting the eye against ultraviolet light-induced damage.

Alcohol Dehydrogenase↗
PubMed1992

The completeness of AIDS case reporting, 1988: a multisite collaborative surveillance project.

OBJECTIVES: The purpose of this study was to evaluate the completeness of acquired immunodeficiency syndrome (AIDS) case reporting. METHODS: Statewide or hospital-specific 1988 medical records were linked with AIDS surveillance in six sites. Medical records were reviewed for persons who had diagnoses suggesting human immunodeficiency virus (HIV) infection or AIDS but were not reported to AIDS surveillance by September 1989. RESULTS: Among 4500 hospitalized persons diagnosed with AIDS through 1988 in the six sites, completeness of reporting was 92% (95% CI = 89%, 96%; range across sites = 89% to 97%). Completeness of reporting was high in males (92%), females (95%), Whites (95%), Blacks (90%), Hispanics (92%), men reporting sexual contact with men (92%), persons reporting injecting-drug use (91%), and persons exposed to HIV through heterosexual contact (99%). In Medicaid enrollees (two states), completeness of reporting was 99% (95% CI = 95%, 99%) in inpatients and 90% (95% CI = 79%, 90%) in outpatients. Of previously reported persons with AIDS, 82% were reported within 5 months of diagnosis. CONCLUSIONS: Completeness of AIDS reporting was high, overall and in each major demographic and HIV exposure group. These results demonstrate that current surveillance data in these six sites provide timely and accurate information regarding persons with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Diagnosis of human immunodeficiency virus infection by enzyme-linked immunospot assays in a prospectively followed cohort of infants of human immunodeficiency virus-seropositive women.

The enzyme-linked immunospot (ELISPOT), a method for quantifying specific and total antibody-secreting cells, was used for the diagnosis of human immunodeficiency virus (HIV) infection in a prospectively followed cohort of infants born to HIV-infected women. From July 1, 1987, to June 1, 1990, 127 infants with known HIV infection status were studied. Seventeen of 22 HIV-infected infants had specific HIV-specific antibody-secreting cells (ASC). Among the infected infants rates of ASC positivity increased during the first year of life, from 25% in the first 5 days of life to 78% after 6 months. Two of the five ASC-negative infected infants were further characterized as hypo- or dysgammaglobulinemic by an adjunct ELISPOT assay for total immunoglobulin-secreting cells. Excluding hypo- or dysgammaglobulinemic infants from the analysis, the rate of ASC positivity among infected infants was 85% (17 of 20) after the age of 6 months. None of the 95 uninfected infants had a positive ELISPOT assay, including 55 who were tested in the first 3 months of life. Thus in this series the specificity was 100%. ELISPOT methodology can be a useful technique for the diagnosis of HIV infection in infants of HIV-seropositive mothers.

Female↗
PubMed1990

Evaluation of putative cytoprotective properties of antiulcer drugs using quantitative histological techniques.

The capacity for cytoprotection has been claimed for a number of drugs that may have a place in the treatment of peptic ulcer disease. In this study we have used quantitative histological criteria to evaluate the ability of these drugs to be cytoprotective and have compared their effects with that of natural prostaglandin E2 (PG). The standard rat model, with injury by instillation of 1 ml of absolute ethanol, has been used. Putative cytoprotective agents were administered 15 min prior to ethanol. Each animal was sacrificed 15 min after ethanol exposure. The stomach was removed and studied using an established quantitative histological technique. This technique provides a measure of the surface area of mucosa damaged and of the volume of mucosa damaged. Ethanol alone caused damage to 76% of the area of the rat stomach and 14% of the volume of the rat gastric mucosa. Pretreatment by PG (25 micrograms/ml) resulted in reduction of the area of damage to 45% and reduction of the percentage volume damage to 2.2%. The synthetic analog of PGE2, Enprostil (1 microgram/ml) achieved similar protective effects. With pretreatment with colloidal bismuth subcitrate (10 mg/kg) or sucralfate (25 mg/kg), no protection against the surface area damaged by ethanol was seen, but there was a marked reduction of the volume of mucosa damaged. Indomethacin pretreatment augmented the damage caused by ethanol. The protective effects of colloidal bismuth subcitrate and sucralfate were not blocked by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Simultaneous assessment of intestinal permeability and lactose tolerance with orally administered raffinose, lactose and L-arabinose.

1. In order to develop an improved differential sugar absorption test for simultaneously assessing intestinal permeability and lactose intolerance, methods were established for determining raffinose, lactose and L-arabinose in human urine. Using NAD(P)H-coupled enzymatic assays and fluorimetry, each sugar was measurable over a concentration range of approximately 3-300 mumol/l in diluted urine specimens. 2. After an overnight fast, 40 normal volunteers drank an iso-osmotic solution containing raffinose, lactose and L-arabinose. The median 5 h urinary sugar excretion was 0.26% of the ingested raffinose, 0.05% of lactose and 17.5% of L-arabinose. 3. In 143 patients with gastrointestinal disease, excretion of both ingested raffinose and lactose was significantly increased in coeliac disease in relapse or in partial remission and in Crohn's disease, but not in the irritable bowel syndrome, coeliac disease in remission or ulcerative colitis. Excretion of lactose, but not raffinose, was increased in patients with mucosal lactase deficiency, whereas excretion of L-arabinose was reduced in all disease groups except ulcerative colitis. 4. Discrimination between diseases was poor when based on individual sugar recoveries, but improved dramatically when excretion was expressed relative to that of L-arabinose. The raffinose/L-arabinose excretion ratio, an index of intestinal permeability, was greater than 0.08 in 15/15 untreated coeliac patients but less than 0.06 in all normal subjects and in 9/9 lactase-deficient patients, 15/16 recovered coeliac patients, 5/6 patients with ulcerative colitis, 13/16 patients with Crohn's disease and 61/62 patients with irritable bowel syndrome.

Adolescent↗
PubMed1990

Treatment of severe chemomechanical erosion using castable ceramic restorations and a new dentin/enamel bonding system: a case report.

Six maxillary anterior teeth demonstrating severe chemomechanical erosion were restored using a minimal preparation design and a castable ceramic. Facial and lingual erosion prevented the development of the opposing wall retention and resistance form needed for traditionally cemented ceramic or porcelain-fused-to-metal crowns. Therefore, a dentin/enamel bonding system was used to condition the enamel and dentin simultaneously prior to cementation of an etched and silanated castable ceramic restoration. A resin cement was used as the luting agent.

Adult↗
PubMed1989

Central nervous system lymphoma: primary lumbar nerve root infiltration.

Primary malignant lymphoma of the central nervous system (CNS) is rare and only infrequently involves the spinal cord, usually in association with multifocal CNS spread. We report a case of primary lymphoma infiltrating lumbar nerve roots without evidence of systemic lymphoma. There has been an excellent response to combined modality therapy, comprising radiotherapy with intrathecal and intravenous cytotoxics. The patient remains well and active 22 months after diagnosis. The literature regarding these rare tumors is reviewed.

Ganglia, Spinal↗
PubMed1989

Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures.

The metaphyseal defects in 40 patients with displaced tibial plateau fractures necessitating surgical repair were filled with either cancellous autograft or interporous hydroxyapatite. Roentgenographic and clinical assessments at follow-up periods averaging 15.4 months (autograft) and 34.5 months (hydroxyapatite) demonstrated no significant differences in the two groups. Interporous hydroxyapatite is a safe, effective alternative to autogenous cancellous bone for the filling of metaphyseal defects associated with tibial plateau fractures.

Adolescent↗
PubMed1988

Porous hydroxyapatite as a bone graft substitute in maxillary augmentation. An histometric study.

A porous HA matrix, which is available for clinical use, was compared with split rib autografts after maxillary contour augmentation in 17 dogs. Specimens were retrieved at 3, 6, 12, 24 and 48 months and undecalcified sections were prepared for microscopy and histometry. The implant and graft cross sectional areas did not change with time, although mechanical trauma caused early changes in implant area in some specimens. In all implants, union with the maxillary cortex occurred along with substantial bone ingrowth. An area under the periosteum contained soft tissue ingrowth. In all grafts, except one, union also occurred. However, bone ingrowth into the cancellous spaces was not apparent, or minimal. The implant specimens were composed of 34.7% HA matrix, 23.9% bone and 41.3% soft tissue. The bone ingrowth remained permanent for the study duration. A 6.5% decrease in HA matrix occurred between the 24 and 48 month time intervals, suggesting the presence of microporous surface resorption. The graft specimens were composed of 55.8% bone and 44.2% non-mineralized tissue, without change over time. The similarity in mineralized tissue composition of the implants (58.6%) and grafts (55.8%) supported the thesis that a porous HA matrix can function as a bone graft substitute.

Animals↗
PubMed1985

The development of a homologous teleost insulin radioimmunoassay and its use in the study of adrenaline on insulin secretion from isolated pancreatic islet tissue of the rainbow trout, Salmo gairdinerii (R.).

A homologous teleost insulin radioimmunoassay (RIA) employing bonito insulin RIA components is described. The RIA sensitivity and specificity was sufficient to measure endogenous immunoreactive insulin (IRI) levels in trout serum, pancreatic islet tissue extract and in vitro culture medium. Adrenaline at 10(-6)M evoked a marked stimulation of basal insulin release from isolated islets; whereas adrenaline at 10(-10)M evoked an inhibition of basal insulin release.

Animals↗