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Biomedical subjects

L Harper

Publications and source records attributed to L Harper.

At least 73 records · Page 4Linked to original sources

Interactions of liguleless1 and liguleless2 function during ligule induction in maize.

The maize ligule is an adaxial membranous structure on the leaf that develops at the boundary of the sheath and blade. The ligule and the associated auricle are dispensable structures, amenable to genetic manipulation. We present here a genetic analysis of liguleless1 (lg1) and liguleless2 (lg2), the two genes known to be uniquely necessary for ligule and auricle development. We show that both reference mutant alleles, lg1-R and lg2-R, are null alleles. The double mutant phenotype suggests that lg1 and lg2 act in the same pathway. Indeed, the dosage of a functional allele at either gene affects the null phenotype of the other. While lg1 function has previously been shown to be cell-autonomous, here we show that the lg2-R phenotype is cell-nonautonomous, suggesting lg1 and lg2 play different roles in the ligule-auricle induction mechanism. We present a model in which early lg2 function specifies the precise position where ligule and auricle will develop. Later lg2 function interacts with lg1 function (either directly or indirectly) to transmit and receive a make-ligule-make-auricle inductive signal.

Alleles↗

Prostate-specific antigen levels in patients receiving long-term dialysis.

OBJECTIVE: To investigate the effect, if any, of renal failure upon prostate-specific antigen (PSA) levels and the validity of PSA estimation as a marker of prostatic disease in renal failure. PATIENTS AND METHODS: PSA was measured in 65 men (median age 67 years, range 39-84) on regular haemodialysis and 37 men (median age 70 years, range 42-77) on continuous ambulatory peritoneal dialysis (CAPD). Patients with a PSA level > 4 ng/mL underwent prostatic biopsy guided by transrectal ultrasonography. RESULTS: There was no evidence of an artefactual elevation of PSA attributable solely to renal failure. All eight patients with a PSA level > 4 ng/mL had prostatic disease. CONCLUSION: PSA measurements in patients with end-stage renal failure treated by dialysis remain a useful marker of prostatic disease.

Adult↗

Nucleotide sequences at recombinational junctions present in pseudorabies virus variants with an invertible L component.

The genome of pseudorabies virus (PrV) consists of two components--a noninvertible long (L) and an invertible short (S) component. The S component is bracketed by inverted repeats. In some variant strains of PrV (which have a selective growth advantage in certain cell lines), a sequence normally present at the left end of the L component has been translocated to the right end of the L component next to the inverted repeat. Consequently, these strains have acquired a genome with an L component that is bracketed by inverted repeats and that also inverts. We have determined the restriction maps and have analyzed the nucleotide sequences of those parts of the genome of three strains with invertible L components that contain the translocated segment of DNA. The results were as follows. The translocated fragments were derived in all cases from the extreme left end of the L component only. The sizes of the translocated fragments were similar, ranging from 1.3 to 1.4 kilobase pairs. The junction between the L and S components in these strains was the same as that in standard viral concatemeric DNA. The translocation of sequences from the left end of the genome next to the inverted repeats was always accompanied by a deletion of sequences from the right end of the L component. The sizes of the deleted fragments varied considerably, ranging from 0.8 to 2.3 kilobase pairs. Sequence homology at the points of recombination, i.e., at the junction between the right end and the left end of the L component, existed sometimes but not always. A model depicting how a virus with a class 2 genome (such as PrV) may acquire a genome with characteristics of a class 3 genome (such as herpes simplex virus) is presented.

Animals↗

Molecular basis for interference of defective interfering particles of pseudorabies virus with replication of standard virus.

Serial passage of pseudorabies virus (PrV) at high multiplicity yields defective interfering particles (DIPs), but the sharp cyclical increases and decreases in titer of infectious virus that are observed upon continued passage at high multiplicity of most DIPs of other viruses are not observed with DIPs of PrV (T. Ben-Porat and A. S. Kaplan, Virology 72:471-479). We have studied the dynamics of the interactions of the virions present in a population of DIPs to assess the cis functions for which the genomes of the DIPs are enriched. The defective genomes present in one population of DIPs, [PrV(1)42], replicate preferentially over the nondefective genomes present in that virion population at early stages of infection, indicating that the DIP DNA is enriched for sequences that can serve as origins of replication at early stages of infection. This replicative advantage of the DIP DNA is transient and disappears at later stages of infection. The defective DNA does not appear to be encapsidated preferentially over the nondefective DNA present in this virion population, which might indicate that it is not enriched for cleavage-encapsidation sites. However, the nondefective DNA in the DIP virion population has become modified and has acquired reiterations of sequences originating from the end of the unique long (UL) region of the genome. Furthermore, both the infectious and defective genomes present in the DIP population compete for encapsidation more effectively than do the genomes of standard PrV. These results indicate that the defective genomes in the population of virions studied are enriched not only for an origin of replication but probably also for sequences necessary for efficient cleavage-encapsidation. Furthermore, the nondefective genomes present in this population of DIPs have also been modified and have acquired the ability to compete with the defective genomes for cleavage-encapsidation.

Capsid↗

cis Functions involved in replication and cleavage-encapsidation of pseudorabies virus.

Serial passage at high multiplicity of pseudorabies virus generates defective interfering particles (DIPs) whose genomes consist at least in part of reiterations of segments of DNA in which sequences originating from different regions of the genome have become covalently linked (F. J. Rixon and T. Ben-Porat, Virology 97:151-163). To determine whether some cis functions present in these reiterated DNA sequences may be responsible for the amplification of DIP DNA, BamHI restriction fragments of this DNA were cloned. These fragments were analyzed and tested for their ability to promote the amplification of covalently linked pBR325 DNA when cotransfected into cells with helper pseudorabies virus DNA. The cloned DIP BamHI DNA fragments consisted of various combinations of sequences originating from either one or both ends as well as sequences from the middle of the unique long (UL) segment of the genome. Only plasmids with inserts consisting of segments of defective DNA originating from the middle of the UL, as well as from both ends of the genome, were able to replicate and be encapsidated autonomously. This finding indicated that signals present at both ends of the genome may be necessary for efficient cleavage-encapsidation. To confirm this observation, we constructed plasmids in which DNA segments containing an origin of replication and sequences from either one or both ends of the virus genome were linked. These experiments showed that efficient cleavage-encapsidation requires the presence of sequences derived from both ends of the genome. Two origins of replication, one at the end of the UL segment and one in the middle of the UL segment, were also identified.

Capsid↗

Sequence of the genome ends and of the junction between the ends in concatemeric DNA of pseudorabies virus.

The nucleotide sequences of the termini of the mature pseudorabies virus genome and of the junction between these termini in concatemeric DNA were compared. To ensure conservation of unmodified 5' and 3' termini, the end fragments obtained directly (uncloned) from mature viral DNA were sequenced. The sequence obtained from 5' and 3' end labeling revealed that whereas the L terminus was blunt ended, the S terminus had a 2-base (GG) 3' overhang. The sequences spanning the junction between the termini present in concatemeric DNA was also determined and compared with that expected when the two ends of the mature DNA were juxtaposed. This comparison showed that in concatemeric DNA the ends of the mature genome had become joined by blunt-end ligation of one of the strands and that the 2-nucleotide gap on the other strand had been repaired. A significant degree of homology between the sequences spanning the junction between the ends of the varicella-zoster virus and pseudorabies virus genomes was found.

Base Sequence↗

[Evaluation of a teaching program of nutrition in agronomy].

The purpose of this study was to evaluate a set of teaching materials on food, nutrition and agriculture, adapted at the Institute of Nutrition and Food Technology (INTA), University of Chile, within the scope of a project with AID and the School of Agronomy of the Chilean Catholic University (U. C.) aimed at incorporating the teaching of human nutrition into the curriculum of Latin American agronomists. A one semester course (54 hours) was given to 22 students of the 7th semester of Agronomy and two Ecuatorian agronomists (with AID scholarships). A set of knowledge evaluation instruments was applied at the beginning and at the end of the course. A total of 83.3% of the students passed the final examination (with more than 75% of correct answers). The difference between the initial and final performance was highly significant (p less than 0.001). According to the students' and teachers' opinions, the general textbook and the teachers book contributed effectively to meet the learning objectives whereas the students handbook needed some modifications. In conclusion, the program is an important contribution to the education of agronomists in a new conception of their role in regard to improvement of the nutritional status and quality of life of the rural population. With a few minor modifications, a final version to be used in the countries of the Region, shall soon become available.

Achievement↗

Antibody affinity chromatography of human proteinases and related proteins.

Antibodies specific for a purified proteinase from the cell-surface of human leukocytes were used to prepare an antibody affinity chromatography column. This column bound a variety of proteins from extracts of human cells and tissues and from human body fluids, indicating that proteins immunologically related to the leukocyte proteinase are widespread in the human body. For human urine and a human fibroblast extract, a single protein species with serine proteinase activity was eluted from the column in each case. Small quantities of a heterogeneous protein fraction were also weakly bound to the column from an extract of mouse submaxillary glands.

Antibodies↗

Intracranial extension and spontaneous hemorrhage of a sphenoid plasmacytoma.

A 71-year-old woman with IgG multiple myeloma presented initially with a compression fracture of the thoracic spine. She responded to radiation therapy and chemotherapy with melphalan and prednisone. One year later, she died from a plasmacytoma eroding intracranially from the greater wing of the sphenoid bone with an associated subdural hematoma. Uncal herniation had been preceded for several weeks by facial numbness. Cranial and intracranial plasmacytomas may occur as isolated lesions or as part of multiple myeloma and can present clinically in a variety of ways, most frequently with cranial nerve palsies. Large intracranial extensions may produce cerebral compression and spontaneous hemorrhage similar to that seen with other malignant intracranial neoplasms. The differential diagnosis of changes in level of consciousness in myeloma patients should include increased intracranial extension and spontaneous hemorrhage.

Aged↗

The effect of lithium chloride on the replication of herpes simplex virus.

Lithium chloride inhibited the replication of type 1 and type 2 Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenze virus.

Antigens, Viral↗

Oxidation of D(minus) lactate by the electron transport fraction of Azotobacter vinelandii.

d(-) Lactate oxidation in Azobacter vinelandii strain O is readily carried out by the membrane bound enzyme that concentrates in the electron transport fraction (R(3)). This oxidation in the R(3) fraction is not dependent on externally added nicotinamide adenine dinucleotide, flavine adenine dinucleotide, or flavine mononucleotide. Phenazine methosulfate, O(2), and menadione all served as good electron carriers, and the oxidation of lactate was limited to the d(-) stereoisomer. Of all the alpha-hydroxyacids examined, only d(-) lactate and d(-) alpha-hydroxybutyrate were oxidized by the R(3) fraction. Paper chromatographic studies revealed that the 2,4-dinitrophenylhydrazine derivative formed from d(-) lactate oxidation was pyruvate. Pyruvate, in turn, could be further decarboxylated nonoxidatively by the R(3) fraction. Spectral studies revealed that both the R(3) flavoprotein and cytochrome (a(2), a(1), b(1), c(4), and c(5)) components were reduced by d(-) lactate. The d(-) lactic oxidase activity was sensitive to electron transport inhibitors, i.e., chlorpromazine, antimycin A, 2-n-heptyl-4-hydroxyquinoline-N-oxide, rotenone, dicumarol, and cyanide, and to a small extent to 4,4,4-trifluoro-1-(2-thienyl)-1,3-butane-dione (TFTB) and Amytal. The d(-) lactic phenazine methosulfate and menadione reductases were sensitive only to dicumarol and TFTB. Chlorpromazine was found to be a highly specific inhibitor of d(-) lactic oxidase activity, 50% inhibition occurring at 6.6 x 10(-6)m.

Antimycin A↗

Treatment of vasculitic IgA nephropathy.

BACKGROUND: Patients with IgA nephropathy and histological vasculitic/crescentic lesions have a poor prognosis. We performed a retrospective study to assess whether treatment with steroids and immunosuppressants would preserve renal function by healing these lesions and thereby prevent progression to glomerular sclerosis and renal failure. METHODS: Sixteen patients with IgA nephropathy and a vasculitic/crescentic glomerulonephritis diagnosed by renal histology were treated with a reducing course of prednisolone (initial dose 60 mg/day). Six patients also received cyclophosphamide (2 mg/kg/day) for three months followed by azathioprine (100 mg/day) in five patients. Ten patients received azathioprine (100 mg/day) in addition to prednisolone. The median duration of treatment was 12 months (range 5-30 months). At the end of treatment each patient had a second renal biopsy. RESULTS: Following treatment there was a significant reduction in the proportion of glomeruli with acute vasculitic lesions from a median of 17.4% (range 4.8-57.5%) to 0 (range 0-15.8%) (p=0.001). There was an increase in the proportion of globally sclerosed glomeruli from a median of 13.4% (range 0-44.4%) to 21.5% (range 0-90%) after treatment but this did not significantly differ from baseline (p=0.24). The proportion of renal cortex with chronic tubular atrophy increased from 2.55% (0.4-57.7%) to 11.3% (0.3-61%) (p=0.09). The median duration of follow-up was 30 months (inter-quartile range 6-30 months). At both 12 and 24 months there was no significant increase in serum creatinine. Four patients, however, developed end-stage renal failure between 24 and 81 months. CONCLUSION: In this retrospective study we show that treatment with steroids and immunosuppressants leads to healing of vasculitic lesions and may thus arrest progression of glomerular scarring.

Adolescent↗