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Biomedical subjects

R Holmes

Publications and source records attributed to R Holmes.

At least 73 records · Page 4Linked to original sources
PubMed1993

Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma.

Neonates born to women with reactive serologic tests for syphilis were studied; the total of 116 included 18 who were symptomatic, 60 asymptomatic but possibly infected, and 38 asymptomatic and probably uninfected. The fluorescent treponemal antibody-absorption (FTA-ABS) 19S IgM test and an IgM capture ELISA for Treponema pallidum, both treponema-specific assays, and the reverse enzyme-linked immunospot (RELISPOT), which detects immunoglobulin-secreting cells and is a nonspecific indicator of infection, were evaluated. Sensitivities among symptomatic neonates were 88% (IgM ELISA), 73% (FTA-ABS), and 78% (RELISPOT). Specificities ranged from 97% to 100%. A major problem has been the inability to identify which asymptomatic but possibly infected neonate is really uninfected. Among 41 such babies who had all three tests done, 93% were negative by all assays, suggesting they were uninfected or recently infected. Strategies to accurately identify the truly uninfected asymptomatic newborn would prevent the unnecessary hospitalization of all at-risk infants, resulting in improved quality of care and reduced costs.

Adult↗
PubMed1993

Effect of insulin-like growth factor-1 on zygomatic arch bone regeneration: a preliminary histological and histometric study.

A number of physicians have attempted to pharmacologically manipulate the healing of bony fractures with a variety of agents such as growth hormone, thyroxine, chondroitin sulfate, and parathyroid hormone. Thus far, results from these experiments have been inconclusive. Previous research dealing with insulin-like growth factors has centered on cultures of osteoblast-like cells and has demonstrated a stimulatory effect on bone collagen synthesis, which may in fact play a critical role in the process of bone formation itself. The purpose of this investigation was to examine the effects of a genetically engineered growth factor, insulin growth factor type I, on midfacial fracture healing. In 24 adult male Sprague-Dawley rats, a standardized defect was created within the midportion of each zygomatic arch. One-half were treated with insulin growth factor type I administered with an osmotic infusion pump and the other half served as control subjects. At 2, 4, 8, and 12 weeks, animals from each group were killed and specimens of the defect obtained. Data were collected from radiographs and histological studies to compare the extent of bony repair. From this study, it appears that insulin growth factor type I could exert a potentiating effect on the repair of midfacial bone defects.

Animals↗
PubMed1993

The effect of insulin growth factor-1 on calvarial sutures in a Sprague-Dawley rat.

Early investigations attempting to determine the exact pathogenesis of premature closure of the cranial sutures were limited by the untoward sequelae caused by surgical procedures in animal models to simulate the development of craniosynostosis. In an attempt to create a model for evaluating the effects of manipulating the craniofacial sutures without the limitations of associated scarring, we conceived an animal prototype dependent on the effects of insulin growth factor-1 on the anterior frontal suture in a Sprague-Dawley rat model. The experimental group received 2 mg of IGF-1 over a 14-day period via a subcutaneously placed osmotic infusion pump, whereas the age-matched control group received no treatment. We present our preliminary histological results describing the effect of IGF-1 on calvarial sutures.

Animals↗
PubMed1993

HIV infection in hospitalized patients and Medicaid enrollees: the accuracy of medical record coding.

To evaluate the accuracy of computerized medical-record coding for human immunodeficiency virus (HIV), medical charts were reviewed in six sites. In 7601 hospital and 867 Medicaid records with a listed diagnosis of HIV, the predictive value for HIV was 91% or higher. HIV was identified in 34% of 1155 Medicaid records listing immune disorder or illness in the acquired immunodeficiency syndrome (AIDS) surveillance definition (without an HIV code). In hospital and Medicaid records, AIDS was identified both in records listing AIDS and records listing HIV without AIDS. HIV codes on hospital and Medicaid records were highly predictive for HIV; undercoding of HIV occurred in Medicaid records.

AIDS-Related Opportunistic Infections↗
PubMed1993

L-asparaginase and PEG asparaginase--past, present, and future.

L-asparaginase is an enzyme which hydrolyses asparagine. Since the 1960s it has been known that some leukemic cells are deficient in asparagine synthetase and therefore cannot manufacture sufficient quantities of this essential amino acid to maintain cell viability. L-asparaginase is predominantly useful in acute lymphocytic leukemia (ALL) although responses have been noted in patients with acute myeloid leukemia, lymphoma, and rarely other tumors. L-asparaginase has been used in conjunction with methotrexate and ara-C in combination programs in leukemia. The major side-effect limiting the usefulness of L-asparaginase is allergic reactions. In addition, it is probable that neutralizing antibodies develop which shorten the half life of the drug so that the goal of depletion of plasma levels of asparagine cannot be attained or maintained. Polyethylene glycol (M.W. 5000) can be conjugated to L-asparaginase at sites not involving the active site of the enzyme. This enables free access of a small molecule, asparagine, to the active site of the enzyme but prevents uptake by the reticuloendothelial system, greatly decreasing the probability of developing antibodies against the asparaginase and prolongs the circulating half life of the drug. In a phase I/II study conducted at the M.D. Anderson Cancer Center, 37 heavily pretreated patients with refractory hematologic malignancy were treated. The age range from 15 to 73 years, median 49 years. Nineteen patients had ALL, 15 lymphoma, two myeloma, and one Hodgkin's disease. The dose levels of PEG L-asparaginase varied from 250 IU/m2 up to 8000 IU/m2. The pharmacokinetic profile demonstrated a monophasic half life consistent with a one compartment model with a single elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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↗