PubMed Health⌕ Search

Biomedical subjects

D Horne

Publications and source records attributed to D Horne.

At least 19 recordsLinked to original sources

In vitro uptake of SCH 27899 (evernimicin) by rat alveolar macrophages.

The in vitro uptake of [(14)C]evernimicin ([(14)C]SCH 27899) by primary cultures of rat alveolar macrophages and hepatocytes was determined. Both cell populations exhibited linear rates of uptake. However, the initial rate of drug uptake by alveolar macrophages was about threefold higher than that by hepatocytes. These findings demonstrate that [(14)C]evernimicin is taken up by rat alveolar macrophages, supporting the likelihood that the drug is able to reach sites of infection.

Aminoglycosides↗

The preparation of copper-oxidized LDL for the measurement of oxidized LDL antibodies by EIA.

In the present study we try to define the optimal conditions for preparation of copper-oxidized low-density lipoprotein (oxLDL) to be used for the assay of oxLDL antibodies by enzyme immunoassay (EIA). Oxidation of LDL was monitored by measuring the formation of conjugated dienes at 234 nm and the generation of fluorescent products with emission at 430 nm when excitation is performed at 360 nm. The generation of immunogenic epitopes was evaluated by testing the reactivity of aliquots collected at different times during the oxidation process with human sera with high oxLDL antibody levels and with a purified human oxLDL antibody. The values of fluorescence emission at 430 nm correlated best with reactivity with oxLDL antibodies; strong reactivity was usually associated with values greater than 1.1 U. The time needed for fluorescence emission to reach maximum levels varied between 6 and 14 h for most LDL, but it was considerably longer in a few LDL preparations. The maximal reactivity of oxLDL with oxLDL antibodies was observed when the LDL oxidation reaction was stopped 4 or more hours after the fluorescence readings reached their peak. At this stage of the oxidation reaction, apolipoprotein B fragmentation and aggregation were observed as shown by Western blot analysis. The CV for 13 EIA runs of two reference oxLDL antibodies reacting with four different pools of standardized oxLDL prepared according to the stated guidelines was 14.5 and 3.9%, confirming the reproducibility of our oxidation conditions.

Antigen-Antibody Complex↗

Maternal serum screening for fetal trisomy 18: a comparison of fixed cutoff and patient-specific risk protocols.

OBJECTIVE: To compare the effectiveness of two widely used protocols for second-trimester screening for fetal trisomy 18. METHODS: Second-trimester screening results for 41,565 women were reviewed to determine whether pregnancies could be considered to be at high risk for trisomy 18. The screening test was considered positive if either maternal serum concentrations of alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3) fell below defined levels, or the second-trimester patient-specific risk (based on maternal age and serum analytes) was greater than 1:100. Detection rates, false-positive rates, and pregnancy outcomes for the two protocols were compared. RESULTS: The fixed-cutoff method showed a 23% detection rate and a 0.19% false-positive rate for trisomy 18. These low rates were in close agreement with a theoretical expectation for fixed-cutoff trisomy 18 screening. The risk-based approach resulted in a 69% detection rate and a 0.45% false-positive rate. Both methods identified pregnancies with other fetal anomalies. CONCLUSION: Overall, the risk-based method is more effective than the fixed-cutoff approach to trisomy 18 screening.

Abnormalities, Multiple↗

Role of Streptococcus thermophilus MR-1C capsular exopolysaccharide in cheese moisture retention.

Recent work by our group has shown that an exopolysaccharide (EPS)-producing starter pair, Streptococcus thermophilus MR-1C and Lactobacillus delbrueckii subsp. bulgaricus MR-1R, can significantly increase moisture retention in low-fat mozzarella (D. B. Perry, D. J. McMahon, and C. J. Oberg, J. Dairy Sci. 80:799-805, 1997). The objectives of this study were to determine whether MR-1C, MR-1R, or both of these strains are required for enhanced moisture retention and to establish the role of EPS in this phenomenon. Analysis of low-fat mozzarella made with different combinations of MR-1C, MR-1R, and the non-EPS-producing starter culture strains S. thermophilus TA061 and Lactobacillus helveticus LH100 showed that S. thermophilus MR-1C was responsible for the increased cheese moisture level. To investigate the role of the S. thermophilus MR-1C EPS in cheese moisture retention, the epsE gene in this bacterium was inactivated by gene replacement. Low-fat mozzarella made with L. helveticus LH100 plus the non-EPS-producing mutant S. thermophilus DM10 had a significantly lower moisture content than did cheese made with strains LH100 and MR-1C, which confirmed that the MR-1C capsular EPS was responsible for the water-binding properties of this bacterium in cheese. Chemical analysis of the S. thermophilus MR-1C EPS indicated that the polymer has a novel basic repeating unit composed of D-galactose, L-rhamnose, and L-fucose in a ratio of 5:2:1.

Base Sequence↗

Down syndrome and neural tube defect screening: the value of using gestational age by ultrasonography.

OBJECTIVE: Our goal was to determine whether gestational age should be based on ultrasonographic evaluation or last menstrual period data in the interpretation of second-trimester maternal serum screening for Down syndrome and open neural tube defects. STUDY DESIGN: Initial and revised screen-positive rates and detection rates were reviewed for women undergoing triple-marker testing (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol). The study population consisted of > 24,000 women at 15.0 to 21.9 weeks' gestation with approximately 60% of test interpretations based on ultrasonographic evaluation of gestational age. Gestational age and screening results were compared for 24 Down syndrome pregnancies in which both ultrasonography and last menstrual period dating were available. RESULTS: Both initial and revised screen-positive rates for Down syndrome were significantly lower when ultrasonographic data were used compared with last menstrual period dating. The detection rate for Down syndrome appeared to be higher with ultrasonographic dating (approximately 76% vs 60% for last menstrual period dating). Down syndrome fetuses had a significantly shorter gestational age when evaluated by ultrasonography (relative to last menstrual period dating), but a similar trend was also seen in control pregnancies. Initial and revised screen-positive rates for open neural tube defects were higher for women who had received an ultrasonographic examination compared with the rates for those women referred with only last menstrual period data. The detection rates for open neural tube defects were similar for both methods of pregnancy dating. CONCLUSION: By use of ultrasonographic measurement of gestational age, the number of amniocenteses performed to detect Down syndrome can be substantially reduced while detection rates are maintained or improved.

Adult↗

Autolysis and cell wall degradation in a choline-independent strain of Streptococcus pneumoniae.

Streptococcus pneumoniae has an auxotrophic requirement for choline, and choline residues that incorporate into the wall and membrane teichoic acids are intimately involved with the control of autolytic phenomena of this bacterium. We report here the re-examination of the role of choline in autolytic cell wall degradation using the choline-independent S. pneumoniae strain R6Cho- recovered from a heterologous cross with DNA from Streptococcus oralis. S pneumoniae Cho- cultured in choline-free medium grew with normal generation time but formed long chains, failed to undergo stationary-phase autolysis, and was also resistant to lysis induced by deoxycholate or penicillin. Cell walls produced under these conditions had reduced phosphorus content, contained no choline residues detectable by nuclear magnetic resonance, and had reduced binding capacity for the pneumococcal autolytic amidase, and complete hydrolysis of such walls by the amidase required prolonged incubation with high concentrations of the enzyme. Addition of choline to the growth medium reversed at these phenomena. High-performance liquid chromatography analysis of amidase digests of cell walls prepared from strain R6Cho- grown with or without choline produced identical stem peptide profiles, which were also similar to that of the parental S. pneumoniae strain R6. Peptidoglycans prepared by hydrofluoric extraction of cell walls from Cho- growth with or without choline or from the parental strain R6 were uniformly susceptible to the autolytic amidase and were fully degraded to the normal family of stem peptides, indicating that, in sharp contrast to the case of cell walls, the amidase degradation of teichoic acid-free peptidoglycan did not require the presence of choline residues in the substrate.

Amidohydrolases↗

Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein.

OBJECTIVE: To evaluate the clinical significance of a second-trimester elevated maternal serum hCG in women carrying singleton, chromosomally normal fetuses. METHODS: The results of second-trimester maternal serum screening (alpha-fetoprotein [MSAFP], hCG, and unconjugated estriol) for 25,438 women were reviewed, and those with hCG values exceeding 3.0 multiples of the median (MoM) were identified. A control population was selected only on the basis of samples accessioned by the laboratory at the same time as the study group. Follow-up information was collected from physicians' offices for both groups. Incidence of fetal or neonatal loss (spontaneous abortion, fetal death, and neonatal death combined), preterm birth (before 37 weeks' gestation), small for gestational age, and preeclampsia were compared. RESULTS: Three hundred twenty-two women (1.3%) had hCG levels exceeding 3.0 MoM. In addition to chromosomal abnormalities and fetal death at the time of testing, this group showed a significantly higher incidence of fetal or neonatal death, preterm birth, low birth weight, and preeclampsia than did controls. For patients with elevated second-trimester hCG, many of the preterm deliveries occurred before 34 weeks' gestation. Logistic regression analysis indicated that hCG, MSAFP, and race were significant independent factors in predicting risk for adverse outcome. CONCLUSIONS: Similar to elevated AFP, elevated hCG is associated with poor pregnancy outcome. By combining the results of the two tests, it may be possible to improve substantially the identification of patients at very high risk for adverse outcomes.

Adult↗

An assessment of sulphide oxidation in abandoned base-metal tailings, Te Aroha, New Zealand.

Tailings from the Tui base-metal mine were characterized using a variety of techniques including scanning electron microscopy (SEM) and flame atomic absorption spectroscopy (FAAS), to assess their potential for use as a plant growth medium. With the notable exception of Pb (10 568 mg kg(-1)), 'total' metal concentrations in the surface tailings (0-200mm) were relatively low (Cu, 113; Fe, 3660; Zn, 486 mg kg(-1)). The theoretical acid generating potential (TAGP) and 'total' concentrations of Cu, Fe and Zn of the tailings, were found to increase greatly with depth, reflecting an increase in the abundance of chalcopyrite (CuFeS(2)), pyrite (FeS(2)) and sphalerite (ZnS), as detected by X-ray diffraction (XRD) analysis. SEM micrographs indicate that the distribution of sulphide minerals in the tailings was originally uniform with depth. The depletion of Cu, Fe and Zn in the surface tailings is considered to be a result of sulphide oxidation, as evidenced by the craggy and highly irregular morphology of the sulphide particles and the high hydrogen ion activity (pH 2.3-4.0) in this zone. The persistence of high concentrations of acid-generating sulphide minerals between 200 and 600 mm has important implications in determining strategies for revegetating the tailings.

Journal Article↗

The need for acute hospitals to provide counselling following motor vehicle accidents.

This paper examines the need for a systematic way of detecting individuals likely to encounter moderate to severe psychological sequelae after being injured in a motor vehicle accident. It presents the findings of assessments of consecutive adult admissions during a six-month period to the Accident and Emergency Department of Royal Melbourne Hospital, a major acute hospital in Melbourne, within two days of being injured in a motor vehicle accident. Seventy of the 250 subjects surveyed completed the General Health Questionnaire 12 and the Impact of Event Scale questionnaire, with 77 per cent found likely to have had a psychiatric disorder. Seventy-four per cent had at least moderate levels of intrusion or avoidance phenomena. Forty-four per cent had severe levels of one or the other. Prevalence of these psychological sequelae was greater than that found in several recent studies on the effects of motor vehicle accidents. A small number (11-15 per cent) sought or received professional counselling within the first three months. This group did not differ, according to levels of intrusion, avoidance, or scores on the GHQ 12, to subjects who did not seek or receive such assistance. Results identify the necessity of investigating and implementing methods of detecting and treating the many who apparently sustain significant psychological sequelae following injury in a motor vehicle accident.

Accidents, Traffic↗

Maternal serum screening for birth defects: results of a Connecticut regional program.

Second trimester maternal serum screening provides a method to identify pregnancies at high risk for fetal Down's syndrome, trisomy 18, open neural tube defects, and a variety of other chromosomal and nonchromosomal fetal anomalies. Results are presented for a regional program to identify high-risk pregnancies using alpha feto-protein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) analyses (triple marker testing). A total of 27,140 women received screening. Using a midtrimester Down's syndrome risk of 1:270 to define the high-risk group, 5.26% of women of all ages were screen-positive for Down's syndrome resulting in the eventual detection of approximately 72% of the affected fetuses. The detection rate for patients under 35 at estimated date of delivery was 61% and for women 35, or older, the detection rate was 100%. A separate protocol to screen for trisomy 18 identified 0.2% of pregnancies, with 38% of the trisomy 18 cases present in this group. Over 3% of women screen-positive for Down's syndrome or trisomy 18 had a serious fetal chromosome anomaly. In addition, 2.89% of women had an elevated AFP (greater or equal to 2.0 multiples of median). This component of the screening resulted in the identification of 86% of the neural tube defects, 75% of the ventral wall defects, and also some of the other various fetal anomalies present in the screened population. Since both laboratory and clinical data are combined to generate patient-specific risks, there is a need for quality control elements that go beyond that normally required for a clinical laboratory alone. We stress the need for comprehensive follow-up programs to evaluate screening programs and maintain high quality.

Biomarkers↗

Prenatal diagnosis of diverse chromosome abnormalities in a population of patients identified by triple-marker testing as screen positive for Down syndrome.

OBJECTIVE: Our purpose was to determine the incidence of all types of chromosome abnormalities (i.e., trisomy 21 and other abnormalities) in women receiving prenatal chromosome analysis after a Down syndrome screen-positive result by maternal serum triple-marker testing (alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol analyses). STUDY DESIGN: A total of 11,434 patients between 15.0 and 21.9 weeks' gestation received second-trimester Down syndrome risk evaluation by triple-marker testing. By use of a 1:270 midtrimester Down syndrome risk cutoff value, and after ultrasonographic confirmation of gestational age, 677 patients were screen positive for Down syndrome (corrected screen-positive rate 5.92%). Karyotypes were reviewed for 468 (69%) of these patients who received prenatal chromosome analysis. RESULTS: In addition to 12 cases of Down syndrome, 12 other fetal chromosome abnormalities were found (i.e., 5.13% had a chromosome abnormality of some type). Expressed as a proportion of all patients with a corrected Down syndrome screen-positive result, at least 3.69% had a chromosome abnormality. The overall spectrum of abnormal karyotypes (approximately 50% autosomal trisomy, 25% structural and 25% sex chromosome abnormality) appears to be comparable to that seen in patients undergoing amniocentesis because of advanced maternal age. CONCLUSIONS: As is the case for women of advanced maternal age, preamniocentesis counseling for patients with positive triple-marker testing results should reflect the relatively high probability that an abnormality other than Down syndrome may be identified.

Adult↗

Juvenile dermatomyositis in a child infected with human parvovirus B19.

We report a case of juvenile dermatomyositis in which clinical onset occurred soon after infection with human parvovirus B19. To the best of our knowledge an association between juvenile dermatomyositis and human parvovirus B19 has not been previously reported. Parvovirus infection has been associated with several autoimmune diseases, and the findings in the case we describe raise the possibility that parvovirus may induce juvenile dermatomyositis, although we could not demonstrate a causal relationship.

Anti-Inflammatory Agents↗

Antibody-dependent enhancement of respiratory syncytial virus infection by sera from young infants.

Respiratory syncytial virus (RSV) convalescent-phase sera and control sera from both infants ( < 6 months) and older individuals (1.5 to 90 years) were assayed for RSV-specific antibodies by neutralization, in vitro enhancing activity, and immunoprecipitation. Enhancement of RSV infection in U937 cells was demonstrated with convalescent-phase sera and was shown to be dependent on Fc receptors by blocking with human immunoglobulin G (P < 0.01). Convalescent-phase sera from infants enhanced infection at concentrations closer to physiological ones (10(-1) to 10(-3) dilutions of serum), while convalescent-phase sera from older individuals enhanced infection only at much lower concentrations (10(-3) to 10(-6) dilutions of serum; P < 0.01). To our knowledge, this is the first report of RSV-enhancing antibody activity in the sera of infants. The observed enhancing activity and the low neutralizing antibody levels are confined mostly to convalescent-phase sera from infants aged 0 to 6 months, suggesting that these factors may contribute to the increased severity of RSV disease frequently encountered in young infants.

Adolescent↗

Conformational and functional analysis of the C-terminal globular head of the reovirus cell attachment protein.

We have been investigating structure-function relationships in the reovirus cell attachment protein sigma 1 using various deletion mutants and protease analysis. In the present study, a series of deletion mutants were constructed which lacked 90, 44, 30, 12, or 4 amino acids from the C-terminus of the 455-amino acid-long reovirus type 3 (T3) sigma 1 protein. The full-length and truncated sigma 1 proteins were expressed in an in vitro transcription/translation system and assayed for L cell binding activity. It was found that the removal of as few as four amino acids from the C-terminus drastically affected the cell binding function of the sigma 1 protein. The C-terminal-truncated proteins were further characterized using trypsin, chymotrypsin, and monoclonal and polyclonal antibodies. Our results indicated that the C-terminal portions of the mutant proteins were misfolded, leading to a loss in cell binding function. The N-terminal fibrous tail of the proteins was unaffected by the deletions as was sigma 1 oligomerization, further illustrating the discrete structural and functional roles of the N- and C-terminal domains of sigma 1. In an attempt to identify smaller, functional peptides, full-length sigma 1 expressed in vitro was digested with trypsin and subsequently with chymotrypsin under various conditions. The results clearly demonstrated the highly stable nature of the C-terminal globular head of sigma 1, even when separated from the N-terminal fibrous tail. We concluded that: (1) the C-terminal globular head of sigma 1 exists as a compact, protease-resistant oligomeric structure; (2) an intact C-terminus is required for proper head folding and generation of the conformationally dependent cell binding domain.

Amino Acid Sequence↗

Identification of conserved domains in the cell attachment proteins of the three serotypes of reovirus.

Sequence analysis of reovirus serotype 1 (ST1) and 2 (ST2) S1 genome segment cDNAs identified several differences from previously reported versions of their sequences. The sequences reported here comprise 1463 and 1440 base pairs, respectively; for comparison, the ST3 S1 genome segment is 1416 nucleotides long. The serotype 1 and 2 sigma 1 proteins are predicted to contain 470 and 462 amino acids, respectively; the ST3 sigma 1 protein is 455 amino acids long. As previously observed, the ST1 and ST2 sigma 1 proteins are much more closely related to each other than to that of ST3 (about 48 and 25% similarity, respectively, using a computer program that finds about 14% similarity among unrelated proteins). The sequences of the three S1 genome segments have diverged very extensively in all three codon positions, in some cases almost to the extent of randomness. Despite this, not only function but also shape and configuration have been retained (since the three sigma 1 proteins can be incorporated efficiently into completely heterologous capsids). Seventy-nine amino acid residues are conserved among all three serotypes, many of them clustered into five regions in which one-third or more of the residues are triply conserved. These regions may represent functionally conserved domains involved in oligomerization, cell attachment, and hemagglutination.

Amino Acid Sequence↗

Incidental carcinoma of prostate, Long-term follow-up.

Stage A1 carcinoma of the prostate because of its small volume and low grade has been regarded as clinically insignificant and requiring no treatment. Recent long-term studies of the untreated natural history of this disease suggests otherwise. Review of our long-term follow-up of untreated incidental carcinoma of the prostate diagnosed between 1966 and 1975 has demonstrated a 16 percent progression rate requiring therapy. This finding suggests Stage A1 prostate carcinoma is not a dismissible diagnosis but demands accurate staging, closer follow-up to uncover progression, and consideration of definitive therapy following diagnosis.

Adenocarcinoma↗