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Biomedical subjects

J Harper

Publications and source records attributed to J Harper.

At least 37 records · Page 2Linked to original sources
PubMed2001

PlantsP: a functional genomics database for plant phosphorylation.

The PlantsP database is a curated database that combines information derived from sequences with experimental functional genomics information. PlantsP focuses on plant protein kinases and protein phosphatases. The database will specifically provide a resource for information on a collection of T-DNA insertion mutants (knockouts) in each protein kinase and phosphatase in Arabidopsis thaliana. PlantsP also provides a curated view of each protein that includes a comprehensive annotation of functionally related sequence motifs, sequence family definitions, alignments and phylogenetic trees, and descriptive information drawn directly from the literature. PlantsP is available at http://PlantsP.sdsc.edu.

Arabidopsis↗
PubMed2001

Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.

PURPOSE: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. RESULTS: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P: = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. CONCLUSION: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

Adolescent↗
PubMed2001

Neuropilin-1 expression in osteogenic cells: down-regulation during differentiation of osteoblasts into osteocytes.

The expression of neuropilin-1 (NRP1), a recently described VEGF and semaphorin receptor expressed by endothelial cells (EC) but some non-EC types as well, was analyzed in osteoblasts in vitro and in vivo. Cultured MC3T3-E1 osteoblasts expressed NRP1 mRNA and bound VEGF(165) but not VEGF(121), characteristic of the VEGF isoform-specific binding of NRP1. These cells did not express VEGFR-1 or VEGFR-2 so that VEGF binding to osteoblasts was strictly NRP1-dependent. In a chick osteocyte differentiation system, NRP1 was expressed by osteoblasts but its expression was absent as the cells matured into osteocytes. Immunohistochemical localization of NRP1 within the developing bones of 36-day-old mice and embryonic Day 17 chicks demonstrated that NRP1 was expressed by osteoblasts migrating alongside invading blood vessels within the metaphysis of the growth plate, as well as by osteoblasts at the developing edge of trabeculae within the marrow cavity. On the other hand, NRP1 was not expressed by osteocytes in either species, consistent with the in vitro results. In addition to osteogenic cells, NRP1 expression by EC was observed throughout the bone. Together these results suggest that NRP1 might have a dual function in bone by mediating osteoblast function directly as well as angiogenesis.

3T3 Cells↗
PubMed2001

Preimplantation genetic diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres.

Preimplantation genetic diagnosis (PGD) requires the combined efforts of geneticists and workers in the field of reproductive medicine. This was studied on the basis of a questionnaire, sent to 35 members of the PGD Consortium of the European Society of Human Reproduction and Embryology (ESHRE). A reply was obtained from 20 centres. They represent the majority of activities in the field of PGD in the world. It is obvious that many of the activities (in vitro fertilisation, embryo culture and biopsy) take place in IVF units while others (counselling and diagnosis) are the responsibility of genetic diagnostic centres. The distances between both units vary considerably. In all but one centre sex determination is offered. Aneuploidy screening is offered in 13 out of 20 centres. PGD of translocations and other structural chromosome abnormalities is offered in all but one centre. The number of monogenic diseases offered varies considerably. In comparison to prenatal diagnosis PGD is more expensive. The majority of these costs are due to the IVF or ICSI procedure. The charges for PGD vary between about 600 euro and 4000 euro. In 16 out of 20 centres the parents to be must sign an informed consent form.

Aneuploidy↗
PubMed2001

First experience of topical SDZ ASM 981 in children with atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokine release under development for the topical treatment of atopic dermatitis. OBJECTIVES: This first paediatric study was designed to measure the systemic exposure to SDZ ASM 981 in young children with atopic dermatitis treated on extensive skin areas. METHODS: Children 1-4 years of age referred to a tertiary care centre for their atopic dermatitis were treated twice daily for 3 weeks with 1% SDZ ASM 981 cream. SDZ ASM 981 blood concentrations were measured on day 4 and 22 (last day) of treatment, and 1 week after the last application, using a radioimmunoassay with a limit of quantification of 0.5 ng mL(-1). Efficacy was assessed by the Eczema Area Severity Index (EASI). RESULTS: The 10 patients included had 23-69% of their body surface area (BSA) affected at baseline. Of the 63 SDZ ASM 981 blood concentrations measured, 63% were < 0.5 ng mL(-1); the maximum value observed was 1.8 ng mL-1. No accumulation was evidenced between days 4 and 22. The first two patients experienced a flare of atopic dermatitis that was not controlled by the study medication. In the other patients, the EASI improved by 8-89% at 3 weeks of treatment. CONCLUSIONS: In these children 1-4 years of age, blood concentrations of SDZ ASM 981 during topical treatment with the 1% cream were consistently low even in the children with the most extensive areas treated (up to 69% of their BSA).

Administration, Cutaneous↗
PubMed2001

Irradiation of diets fed to captive exotic felids: microbial destruction, consumption, and fecal consistency.

Two frozen, raw horse meat-based diets fed to captive exotic felids at Brookfield Zoo were irradiated to determine the extent of microbial destruction and whether radiation treatment would affect consumption and/or fecal consistency in exotic cats. Fifteen cats, two African lions (Panthera leo), two Amur tigers (Panthera tigris altaica), one Amur leopard (Panthera pardus orientalis), two clouded leopards (Neofelis nebulosa), two caracals (Felis caracal), one bobcat (Felis rufus), and five fishing cats (Felis viverrinus), housed at Brookfield Zoo were fed nonirradiated and irradiated raw diets containing horse meat with cereal products and fortified with nutrients: Nebraska Brand Feline and/or Canine Diet (Animal Spectrum, North Platte, Nebraska 69103, USA). Baseline data were obtained during a 2-wk control period (nonirradiated diets), which was followed by a 4-wk period of feeding comparable irradiated diets. Feed intake and fecal consistency data were collected. An estimated radiation dose range of 0.5-3.9 kilograys reduced most microbial populations, depending on specific diet and microbe type. Irradiation had no overall effect on either feed consumption or fecal consistency in captive exotic cats, regardless of species, age, sex, or body mass. Data indicate that irradiation of frozen horse meat-based diets (packaged in 2.2-kg portions) result in microbial destruction in these products but that product storage time between irradiation and sampling may also affect microbial reduction. However, irradiation would be an appropriate method for reducing potentially pathologic bacteria in raw meat fed to exotic cats.

Animal Feed↗
PubMed2001

Life cycle of a data warehousing project in healthcare.

Hill Physicians Medical Group (and its medical management firm, PriMed Management) early on recognized the need for a data warehouse. Management demanded that data from many sources be integrated, cleansed, and formatted. As a first step, an operational data store (ODS) was built and populated with data from the main transactional system; encounter data were added. The ODS has served its purpose well and has whetted management's appetite for more information and faster, more reliable access, all in one location. PriMed hired Annams Systems Consulting (Annams) for this effort. A team was formed, made up of consultants from Annams and members of PriMed's information services (IS) team. The "classical" approach is being taken: enhancing the ODS, which is largely normalized in structure, and integrating data from various sources, along with enforcing business rules. The team is designing and implementing data marts and a "star schema" style of data modeling--a useful tool for management to evaluate results before investing further.

California↗
PubMed2000

Origin of antimony segregation in GaInSb/InAs strained-layer superlattices

We show how cross-sectional scanning tunneling microscopy may be used to reconstruct the Sb segregation profiles in GaInSb /InAs strained-layer superlattices. These profiles are accurately described by a one-dimensional model parametrizing the spatial evolution of an Sb seed at the InAs-on-GaInSb interface in terms of two-anion-layer exchange. We argue that the segregation seed, which decreases from 2 / 3 to 1 / 2 monolayer when growth conditions are made less anion rich, has its origin in the Sb-bilayer reconstruction maintained during GaInSb epitaxy.

Journal Article↗
PubMed2000

Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model.

Among the earliest and most important stages during tumorigenesis is the activation of the angiogenic process, an event that is termed the "switch to the angiogenic phenotype." We have developed an in vivo system that can reliably recapitulate the stages in tumor development that represent this transition. Using this model, we have harvested and studied tumor nodules that can be distinguished from each other on the basis of their degree of vascularization. Angiogenic tumor nodules were characterized by the presence of capillary vessels as determined by factor VIII immunohistochemistry, and both angiogenic and proteolytic activities in vitro. In contrast, preangiogenic nodules were devoid of microvessels and showed little angiogenic or proteolytic activity in vitro. Addition of a specific metalloproteinase inhibitor resulted in the abrogation of both angiogenic and proteolytic activities of the angiogenic nodules in vitro. Comparative substrate gel electrophoresis detected the presence of a prominent matrix metalloproteinase (MMP-2) in the angiogenic nodules when compared with the preangiogenic ones. Suppression of MMP-2 activity by antisense oligonucleotides in the vascular nodules resulted in the loss of angiogenic potential both in vitro and in vivo in the chick chorioallantoic membrane assay. Moreover, this suppression of MMP-2 activity in angiogenic nodules inhibited tumor growth in vivo by approximately 70%. These results strongly implicate the activity of MMP-2 as a requirement for the switch to the angiogenic phenotype and validate this model as a reliable and reproducible tool by which to study other cellular and biochemical factors involved in the acquisition of the angiogenic phenotype.

Animals↗
PubMed2000

Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina.

[formula: see text] The endophytic fungus Cryptosporiopsis cf. quercina produces cryptocin in culture. Among other fungi, this unique tetramic acid displays antimycotic activity against Pyricularia oryzae, the causal agent of rice blast disease. Cryptocin also possesses activity against a wide variety of plant pathogenic but not human pathogenic fungi. The fine rhomboid-like crystals of cryptocin allowed structural elucidation by X-ray crystallography. The importance of cryptocin to the symbiotic relationship of C. quercina to its hosts is briefly discussed.

Ascomycota↗
PubMed2000

Loperamide: novel effects on capacitative calcium influx.

Loperamide is a widely used antidiarrheal that primarily acts at nanomolar concentrations through activation of opioid receptors in the gastrointestinal tract. At somewhat higher concentrations, loperamide blocks calmodulin activity, calcium channels, N-methyl-D-aspartate-receptor channels, and maitotoxin-elicited calcium influx. Loperamide at micromolar concentrations has now been shown to have a remarkable stimulatory effect on the capacitative calcium influx that is triggered in many cells by depletion of the inositol-trisphosphate-sensitive stores of calcium in the endoplasmic reticulum. The mechanism whereby loperamide enhances levels of intracellular calcium elevated by capacitative calcium influx is, as yet, undefined.

Adenosine Triphosphate↗
PubMed2000

Chromosomal localization of cotransformed transgenes in the hexaploid cultivated oat Avena sativa L. using fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) was used to localize two transgenes (gus and bar), carried on plasmids pACT-1F and pUBA, respectively, on mitotic metaphase squashes of T1 plants of the cultivated hexaploid oat Avena sativa L. cotransformed by microprojectile bombardment of embryogenic callus. Among the eight progeny analysed by FISH in each of two lines, we detected plants null, hetero- and homozygous for the two genes in one line, and plants null and heterozygous for the two genes in the other line. Our results demonstrated that in the two independent transformation events, the gus and bar genes had inserted in the same position relative to each other. In each transformation event, the insertions occurred on D satellite (SAT) chromosomes bearing a C genome translocation.

Avena↗
PubMed2000

ESHRE preimplantation genetic diagnosis (PGD) consortium: data collection II (May 2000).

In 1997, the ESHRE PGD Consortium was formed as part of the ESHRE Special Interest Group on Reproductive Genetics, in order to undertake a long-term study of the efficacy and clinical outcome of preimplantation genetic diagnosis (PGD). In December 1999, the first PGD Consortium report was published discussing referrals of 323 couples, 392 PGD cycles and 82 pregnancies and 79 children born. In the second round of data collection, contributing centres were asked to send in data from their PGD activities before January 1997, as well as from 1st October 1998 until 1st May 2000, in order to have as complete as possible an overview of PGD practices in these centres. A further 563 referrals were sent in as well as 926 PGD cycles, and data on 89 pregnancies (including seven pregnancies ongoing from the previous group) and 83 children were collected. This has led to a considerable amount of cumulative data being acquired: over a period of 7 years (the oldest PGD cycle reported dates from 1994), referral data on 886 couples, cycle data on 1318 PGD cycles and data on 163 pregnancies and 162 babies were collected. In all, these data are encouraging: they show first, that the practice of PGD is becoming more and more established, and an increasing number of different applications is emerging; and second, that collecting these data is worthwhile, as they will be a valuable source of information for all those involved, e.g. in counselling patients and interacting with governmental bodies.

Aneuploidy↗
PubMed2000

A randomized controlled trial of strapping to prevent post-stroke shoulder pain.

OBJECTIVE: To determine whether strapping the shoulder in hemiplegic stroke patients: (1) prevents the development, or reduces the severity, of shoulder pain, (2) preserves range of movement in the shoulder, and (3) improves the functional outcomes for the arm and patient overall. DESIGN: A prospective, randomized, single-blind controlled trial of shoulder strapping versus no strapping. SETTING: Care of the elderly wards in a teaching hospital, Christchurch, New Zealand. SUBJECTS: All patients admitted with an acute hemiplegic stroke, who had persisting weakness of shoulder abduction. INTERVENTION: The treatment group had their affected shoulder strapped for six weeks from randomization in addition to standard physiotherapy. MAIN OUTCOME MEASURES: All subjects were assessed at entry (week 0), at end of the treatment phase (week 6) and two months later (week 14). A visual analogue scale (VAS) was used to assess shoulder pain severity whereas shoulder range of movement to the point of pain (SROMP) assessed passive range of movement and pain. Functional Independence Measure (FIM), Motor Assessment Scale (MAS) and Rankin Disability Index measured functional outcomes. RESULTS: Ninety-eight subjects participated (49 strapped, 49 controls). Intention to treat analysis showed no significant difference in pain, range of movement or functional outcomes after the intervention phase or at the final assessment. However there were trends for less pain at six weeks (VAS, p = 0.11) and better final upper limb function (MAS, p = 0.16) in strapped patients. Skin reactions were uncommon (6.1%). The presence of neglect or sensory loss, but not subluxation, at baseline was independently associated with poor outcome. Range of movement was lost early (mean difference SROMP between hemiplegic and contralateral shoulders at baseline = 15.2 degrees (95% CI 10.9-19.5)) and continued throughout the study. Shoulder strapping did not alter the rate at which range of movement was lost. CONCLUSIONS: No significant benefit with shoulder strapping was demonstrated and reasons for this are discussed. Range of movement in the hemiplegic shoulder is lost very early and any preventive treatments need to begin within the first 1-2 days after a stroke.

Aged↗
PubMed2000

Diagnosis and treatment of a fractured third phalanx in a Masai giraffe (Giraffe camelopardalis tippelskirchi).

A 10-yr-old male Masai giraffe (Giraffe camelopardalis tippelskirchi) presented with acute right forelimb lameness. Radiographs revealed a fracture of the medial claw of the distal phalanx penetrating into the distal interphalangeal joint. The giraffe was sedated while it was standing in a chute, and a wooden "hoof block" was applied to the lateral claw of the same limb. The animal was no longer lame 3 days after the procedure. Subsequent treatments included vitamin E, phenylbutazone, and glycosaminoglycans. For 7 wk it was maintained in a small holding yard on packed sand during the day and on deep sand during the night. The hoof block slowly wore down, and at 7 wk, it was placed back on concrete in the evening. At 8 wk, the block had completely worn off and the animal was no longer lame, but radiographs indicated minimal fracture healing. Radiographs performed at 7 mo indicated that there was still a radiolucent zone at the fracture line but calcification was evident at the margins of the fracture.

Animal Diseases↗