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Biomedical subjects

M Levine

Publications and source records attributed to M Levine.

At least 397 records · Page 22Linked to original sources
PubMed1988

Infection with Candida albicans of a total knee arthroplasty. Case report and review of the literature.

Infection with Candida albicans of a total knee arthroplasty developed in an immunosuppressed 52-year-old woman with rheumatoid arthritis who initially presented with clear drainage from the incision, which cultured negative initially. Successful treatment consisted initially of debridement and a course of intravenous antibiotics, followed by staged arthrodesis with an intramedullary rod.

Anti-Bacterial Agents↗
PubMed1988

Evaluation of serum phenytoin monitoring in an acute care setting.

Serum phenytoin monitoring is frequently used in the management of epileptic patients because phenytoin has a narrow therapeutic index and exhibits nonlinear pharmacokinetics. This study prospectively evaluated serum phenytoin monitoring in an acute care teaching hospital. Two sets of criteria were established a priori to define (a) appropriate selection of patients with regard to serum phenytoin monitoring, and (b) inappropriate serum phenytoin determinations (SPDs). Eighty patients receiving phenytoin were studied, of whom 58 (72.5%) were appropriately selected. These included 35 patients (43.8%) for whom monitoring was indicated and was performed, and 23 patients (28.7%) for whom monitoring was not indicated and was not performed. There were 39 patients with no indications for serum phenytoin monitoring; however, 16 (41%) of them were monitored. A total of 113 SPDs were performed, of which 83 (73.5%) were deemed to be inappropriate. Seventy percent of SPDs resulted in phenytoin concentrations outside the usual therapeutic range (10-20 micrograms/ml). Overall, physicians appropriately selected patients with regard to serum phenytoin monitoring; however, when inappropriate selection did occur, it tended to involve monitoring of patients who did not require it. The majority of SPDs performed were deemed to be inappropriate, since they were done too soon after admission or a change in therapy to reliably indicate steady-state serum concentrations.

Acute Disease↗
PubMed1987

Comparison of one- and two-dose regimens of influenza vaccine for elderly men.

In November and December 1984, 102 male residents of a long-term care facility (mean age 74.6 [extremes 59 and 97] years) received 0.5 ml of trivalent inactivated whole-virion influenza vaccine, containing 15 micrograms of the hemagglutinin of each of A/Philippines/2/82 (H3N2), A/Chile/83 (H1N1) and B/USSR/83. A second dose of the vaccine was administered to a subgroup of 55 randomly chosen subjects 8 weeks later. Serum samples were collected from all the subjects before and 4, 8, 12 and 16 weeks after administration of the first dose and were assayed for hemagglutinin-inhibiting (HAI) antibody to each of the three antigens. At 8 weeks there were significant increases (p less than 0.05) in the geometric mean titre of antibody and in the proportion of subjects with HAI antibody titres of 1:40 or more (except to the B/USSR antigen) in both groups. There were no differences between the groups at 8 weeks or at 16 weeks (8 weeks after administration of the second dose of vaccine) in the frequency of seroconversion, the geometric mean titre or the proportion of subjects with HAI antibody titres of 1:40 or more. Overall, 60%, 32% and 13% of the 102 subjects had titres of 1:40 or more to the A/Philippines, A/Chile and B/USSR antigens respectively at 16 weeks. The results suggest that a second dose of influenza vaccine given 8 weeks after the first does not enhance the immune response in elderly men and that a substantial proportion of this population remains unprotected against infection (having HAI antibody titres of less than 1:40) during the influenza season.

Adult↗
PubMed1987

Rapid identification of nonessential genes of herpes simplex virus type 1 by Tn5 mutagenesis.

The large genome of herpes simplex virus type of (HSV-1) encodes at least 80 polypeptides, the majority of which have no recognized function. A subgroup of these gene products appears to be nonessential for virus replication in cell culture, but contributes to the complex life cycle of the virus in the host. To identify such functions, a simple insertional mutagenesis method has been used for selective inactivation of individual HSV-1 genes. The bacterial transposon Tn5 was allowed to insert randomly into cloned restriction fragments representing the entire short unique (US) region of the HSV-1 genome. Of the 12 open reading frames that were mutagenized with Tn5, mutant derivatives of US2, US4, and US5 were recombined into the virus. These three genes proved to be nonessential for HSV-1 replication in Vero (African Green monkey kidney) cells and the US4 gene appeared to be involved in viral pathogenesis in the central nervous system of mice. This rapid mutagenesis procedure should prove useful in exploring the entire HSV-1 genome as well as the genomes of other complex animal viruses.

DNA Restriction Enzymes↗
PubMed1987

Regulation of the herpes simplex virus type 1 late (gamma 2) glycoprotein C gene: sequences between base pairs -34 to +29 control transient expression and responsiveness to transactivation by the products of the immediate early (alpha) 4 and 0 genes.

The glycoprotein C (gC) gene of herpes simplex virus type 1 is a true late gene, in that its expression occurs late in infection with a strict requirement for viral DNA replication. Recently, we reported on gC expression during infection with mutant viruses carrying deletions in the gC gene promoter. Analysis of RNA extracted from cells infected with individual mutants showed that the DNA sequences required for regulated expression of this late gene lie within bases -34 to +124 relative to the 5' end of the mRNA. In the present study, the deleted gC promoter sequences were fused to the bacterial chlorampheniol acetyltransferase (CAT) gene and expression was measured in short-term transfection assays after transactivation by infection with HSV or cotransfection with a second plasmid carrying the immediate early genes of HSV-1. The 63 base pair sequence located between -34 to +29 on the gC promoter was sufficient to give induction of CAT activity following infection and on cotransfection with plasmids which code for the immediate early gene products ICP4 and ICPO. This 63 base pair region contains the TATA homology and the transcriptional start site of the gC gene, and apparently contains specific promoter elements not found in a similar region of the HSV TK promoter. This was shown by removing the distal upstream region of the TK promoter, 5' to -37, and found that the TK gene was no longer activated by infection or cotransfection with an alpha 4-alpha 0 gene containing plasmid.

Animals↗
PubMed1987

Purification and structural characterization of herpes simplex virus glycoprotein C.

Purification of herpes simplex virus glycoprotein C (gC) in microgram amounts yielded sufficient material for an analysis of its secondary structure. Purification was facilitated by using the mutant virus gC-3, which bears a point mutation that interrupts the putative hydrophobic membrane anchor sequence, causing the secretion of gC-3 protein into the cell culture medium. gC-3 protein was purified by size fractionation of concentrated culture medium from infected cells on a gel filtration column of Sephacryl S-200, followed by immunoaffinity chromatography on a column constructed of gC-specific monoclonal antibodies cross-linked to a protein A-Sepharose CL-4B matrix. Purified gC-3 had a molecular weight of 130,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the size expected for gC, was reactive with gC-specific monoclonal antibodies in protein immunoblots, and contained amino acid sequences characteristic of gC as determined by radiochemical amino acid microsequence analyses. Polyclonal antisera obtained from a rabbit immunized with gC-3 reacted with wild-type gC in immunoprecipitation, enzyme immunoassay, and immunoelectroblot (western blot) assays. Deglycosylation by treatment with trifluoromethanesulfonic acid reduced the molecular weight of gC-3 by approximately 35%. Analyses of both native and deglycosylated gC-3 by Raman spectroscopy showed that the native molecule consists of about 17% alpha-helix, 24% beta-sheet, and 60% disordered secondary structures, whereas deglycosylated gC-3 consists of about 8% alpha-helix, 10% beta-sheet, and 81% disordered structures. These data were in good agreement with the 11% alpha-helix, 18% beta-sheet, 61% beta-turn, and 9% disordered structures calculated from Chou-Fasman analysis of the primary sequence of gC-3.

Amino Acid Sequence↗
PubMed1987

Characterization and localization of the even-skipped protein of Drosophila.

On the basis of homeo box cross-homology we have isolated the pair-rule gene even-skipped (eve) of Drosophila. The eve transcription unit appears to be less than 1.5 kb in length, and encodes a single mRNA of approximately 1.4 kb. The nucleotide sequence of genomic and cDNA clones indicates that the eve protein is composed of 376 amino acid residues, and that its homeo domain shares only approximately 50% amino acid identity with the homeo domains of previously characterized genes. Using antibodies raised against a beta-galactosidase fusion protein we show that the eve protein is distributed in a series of seven transverse stripes at the cellular blastoderm stage, and is localized primarily within the nuclear regions of those embryonic cells that express the gene. After gastrulation, seven weakly stained stripes of eve expression appear, resulting in a transient pattern that consists of a total of 14 evenly spaced stripes. Both the original and new stripes gradually disappear during germ band elongation. A second expression pattern emerges during neurogenesis, whereby eve protein is detected in discrete subsets of neurons in each of the ventral ganglia.

Amino Acid Sequence↗
PubMed1987

Echocardiographic estimate of left atrial pressure in children.

Echocardiographic estimates of left atrial pressure using the Q-MVC/AVC-E ratio were obtained from 21 patients in the early postoperative period and compared to simultaneously recorded mean left atrial pressure. A good correlation was obtained between mean left atrial pressure and the Q-MVC/AVC-E ratio (r = 0.81, p less than 0.001) with a regression equation of: left atrial pressure = 11.09 (Q-MVC/AVC-E) + 0.84. The present data compared to those of previous investigators reveal that, although there are quantitative differences between each of the studies, the correlation coefficient of each study is good. Echocardiography provides a useful noninvasive estimate the left atrial pressure; however, each laboratory must establish its own normals.

Blood Pressure↗
PubMed1987

Evaluation of a nomogram for estimating the rate of phenytoin accumulation.

This study evaluated a nomogram designed to identify a subgroup of the patients whose serum phenytoin concentrations are near steady state at a given time after initiation of therapy. A sample of 95 adult subjects with reported values of Vmax and Km was pooled from the literature, and computer simulations of phenytoin accumulation for 15 days after initiation of phenytoin acid at 300 mg/day were performed. Simulated serum concentrations on days 5, 10, and 15 were used to identify subjects who were predicted by the nomogram to be at greater than or equal to 83% of steady state, and these results were compared with those expected from the Michaelis-Menten model. In the simulations, 42, 62, and 66 subjects reached greater than or equal to 83% of steady state by days 5, 10, and 15, respectively. The nomogram correctly identified 13 (31.0%), 33 (53.2%), and 43 (65.2%) of these individuals, respectively. The frequency of erroneous predictions was low, even in subjects whose Km and volume of distribution were outside the limits set in the development of the nomogram. Use of a nomogram such as this would help a subgroup of patients to attain a desired serum phenytoin concentration earlier in therapy and with fewer serum phenytoin determinations than would otherwise be required. It would also prevent premature increases in phenytoin dose in patients whose serum concentration is still rising.

Adult↗
PubMed1987

Interindividual variation in the extent and rate of phenytoin accumulation.

Steady-state serum phenytoin concentration (Css) is known to increase nonlinearly with dose, but it is less well recognized that the rate of phenytoin accumulation is also dose dependent. This stimulation study estimated the extent and rate of phenytoin accumulation in a sample of 95 adult subjects, with known values of Vmax and Km, pooled from the literature. Simulations were done using a Michaelis-Menten model and phenytoin sodium doses of 200, 300, and 400 mg/day. The distributions of Css and the time required to reach 90% of steady state (T90) became increasingly positively skewed as dose was increased. The T90 and Css were positively correlated (r greater than or equal to 0.8880, p less than 0.00001) and subjects reached 90% or more of Css more slowly as the initial phenytoin dose was increased. At an initial dose of 300 mg/day of phenytoin sodium, mean Css was 11.0 +/- 9.10 micrograms/ml (median, 7.62 micrograms/ml), and mean T90 was 12.2 +/- 15.4 days (median, 5.98 days). Only 25.3% of the subjects would be expected to achieve therapeutic serum concentrations (10-20 micrograms/ml) on this dose, and 88.4% would reach 0.9 Css within 30 days. Phenytoin dosage must be individualized to achieve concentrations of 10-20 micrograms/ml. Multiple serum phenytoin determinations during the first 30 days or more are required to determine that steady state has been reached, but these need not be done more often than once a week.

Adolescent↗
PubMed1987

Molecular characterization of the zerknüllt region of the Antennapedia gene complex in Drosophila.

zerknüllt (zen) is unique among the 18 known homeo box genes in Drosophila since it is required for the differentiation of the dorsal-ventral pattern, and does not appear to be involved in the process of segmentation. Here we show that the zen region of the Antennapedia complex (ANT-C) consists of two closely linked homeo box genes, designated z1 and z2. The z1 and z2 transcription units show essentially identical patterns of expression during early development, which are consistent with the timing and sites of zen+ gene activity. The putative proteins encoded by z1 and z2 are highly divergent and are related only by virtue of homeo box homology. We have used P-element-mediated germ line transformation to show that z1 alone can provide zen+ gene function, suggesting that the z2 gene might be dispensable. The occurrence of closely linked homeo box genes that display similar patterns of expression is not unique to the zen locus. Such gene duplications might provide important clues to the evolution of the homeo box gene family in Drosophila and other organisms.

Amino Acid Sequence↗
PubMed1987

Complementary patterns of even-skipped and fushi tarazu expression involve their differential regulation by a common set of segmentation genes in Drosophila.

We have examined the position-dependent expression of two segmentation genes that contain a homeo box, even-skipped (eve) and fushi tarazu (ftz). Products encoded by both genes accumulate in a series of seven transverse stripes along the anterior-posterior body axis of developing embryos. Double-staining experiments show that eve and ftz proteins accumulate in complementary sets of embryonic cells. A total of eight zygotically active segmentation genes are required for the establishment and refinement of the eve and ftz expression patterns during development. Mutations that affect one of the genes were always found to produce a reciprocal alteration in the other. These results suggest that the eve and ftz promoters independently "interpret" the same positional cues to give differential patterns of expression. We propose that a combination of segmentation gene products that activates the expression of eve represses the expression of ftz, and vice versa. This proposal is discussed in the context of a hierarchy of interactions among segmentation genes, whereby the gap genes establish asymmetric patterns of eve and ftz expression in blastoderm-stage embryos, and interactions with other pair-rule genes serve to refine further the complementarity of eve and ftz expression during gastrulation and germ band elongation.

Animals↗
PubMed1987

Characterization and cross-reactivity of rabbit antisera to plaque toxins.

The effects of heat labile, high molecular weight water-soluble toxins from bacterial plaque on HL60 promyelocytic cells were examined. On gel filtration, four inhibitors of HL60 cell growth and two inhibitors of HeLa cell growth (PT1, PT2) were detected. The first and third HL60 cell inhibitors corresponded to the two HeLa cell inhibitors. The last eluted HL60 cell inhibitor (plaque leukotoxin, PL) did not inhibit HeLa cell growth. Anti-PT2 antibodies reduced the activity of enriched PT2 by 20-50%, but all other antisera tested exhibited no effect. Anti-PL antibodies detected antigens from Actinobacillus actinomycetemcomitans, although anti-A. actinomycetemcomitans and anti-Capnocytophaga sputigena antibodies did not react with plaque extract. These findings suggest that the plaque toxins examined in this study were probably not derived from these two bacteria.

Aggregatibacter actinomycetemcomitans↗
PubMed1987

Characterization of the immune response to trivalent influenza vaccine in elderly men.

This study characterizes the time course of the immune response to influenza vaccine in elderly men. Sixty-two men aged 58 to 91 years (mean, 74.3 years) were vaccinated with trivalent inactivated influenza vaccine in the fall of 1983. Serum hemagglutinin-inhibiting (HAI) antibody titers were measured at various times up to 24 weeks postvaccination. Seroconversion frequencies determined at single times after vaccination were 28 to 46% of subjects, whereas cumulative seroconversion frequencies were greater than or equal to 70%. Eighteen to 28% of seroconversions occurred later than four weeks, and greater than or equal to 68% of those who seroconverted experienced greater than four-fold declines in peak HAI antibody titers by 24 weeks after vaccination. Consequently, 31 to 73% of subjects had HAI antibody titers greater than 40 throughout the study period. Measurement of HAI antibody titers at only one time after vaccination may not adequately reflect the immune response of this population or the degree of protection maintained through the influenza season.

Age Factors↗
PubMed1987

Ascorbic acid: the concept of optimum requirements.

Experiments with enzymes in situ that are dependent on ascorbic acid for maximum activity will provide critical information about ascorbic acid requirements. Our work with chromaffin tissue as a model system eventually will result in the determination of two dose-response curves for norepinephrine biosynthesis, representing cytosolic ascorbic acid and intragranular ascorbic acid (Fig. 11). These curves for norepinephrine biosynthesis can be combined with curves for other enzymatic events that are also dependent on ascorbic acid for maximal activity. These dose-response curves (Fig. 2) will allow determination of optimum ascorbic acid requirements based on specific product formation and minimum toxicity. These principles are adaptable to other vitamins as well as ascorbic acid, and could form the basis for a new approach to vitamin requirements.

Adrenal Medulla↗