Search PubMed⌕ Search

Biomedical subjects

J Greer

Publications and source records attributed to J Greer.

At least 19 recordsLinked to original sources
PubMed2001

Alterations in habituation of the tail flip response in epigean and troglobitic crayfish.

We demonstrate that the probability of the crayfish, P. clarkii, to tail flip in response to a touch on the dorsal tail fan is dependent on both the size and the behavioral state of the animal. Alterations in the animal's internal physical state, such as when the animal autotomizes its chelipeds, will cause larger-sized animals to tail flip; if they were not autotomized, then no tail flip response would occur. Altering the external environment by removal of water causes small crayfish, which normally habituate slowly, to rapidly habituate. Observation of large adult crayfish in a species, O. australis packardi, one that evolved to live in total cave darkness, revealed that they are more likely to tail flip than are the sighted, adult P. clarkii. Results indicate that the behavioral state of the crayfish can result in rapid and long-term alterations in the tail flip response and in habituation rates to repetitive stimuli. This ability to show plasticity in gain setting may be regulated by neuromodulators and can occur in large adults of the sighted crayfish. Differences between the two species indicate that size may not be the sole contributing factor to account for tail flip behaviors. J. Exp. Zool. 290:163-176, 2001.

Animals↗
PubMed2001

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/m2/d [corrected]. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P =.016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

Acute Disease↗
PubMed2000

Automated crystal mounting and data collection for protein crystallography.

To increase the efficiency of diffraction data collection for protein crystallographic studies, an automated system designed to store frozen protein crystals, mount them sequentially, align them to the X-ray beam, collect complete data sets, and return the crystals to storage has been developed. Advances in X-ray data collection technology including more brilliant X-ray sources, improved focusing optics, and faster-readout detectors have reduced diffraction data acquisition times from days to hours at a typical protein crystallography laboratory [1,2]. In addition, the number of high-brilliance synchrotron X-ray beam lines dedicated to macromolecular crystallography has increased significantly, and data collection times at these facilities can be routinely less than an hour per crystal. Because the number of protein crystals that may be collected in a 24 hr period has substantially increased, unattended X-ray data acquisition, including automated crystal mounting and alignment, is a desirable goal for protein crystallography. The ability to complete X-ray data collection more efficiently should impact a number of fields, including the emerging structural genomics field [3], structure-directed drug design, and the newly developed screening by X-ray crystallography [4], as well as small molecule applications.

Crystallization↗
PubMed2000

Discovering novel ligands for macromolecules using X-ray crystallographic screening.

The need to decrease the time scale for clinical compound discovery has led to innovations at several stages in the process, including genomics/proteomics for target identification, ultrahigh-throughput screening for lead identification, and structure-based drug design and combinatorial chemistry for lead optimization. A critical juncture in the process is the identification of a proper lead compound, because a poor choice may generate costly difficulties at later stages. Lead compounds are commonly identified from high-throughput screens of large compound libraries, derived from known substrates/inhibitors, or identified in computational prescreeusing X-ray crystal structures. Structural information is often consulted to efficiently optimize leads, but under the current paradigm, such data require preidentification and confirmation of compound binding. Here, we describe a new X-ray crystallography-driven screening technique that combines the steps of lead identification, structural assessment, and optimization. The method is rapid, efficient, and high-throughput, and it results in detailed crystallographic structure information. The utility of the method is demonstrated in the discovery and optimization of a new orally available class of urokinase inhibitors for the treatment of cancer.

Administration, Oral↗
PubMed2000

Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group.

Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.

Adult↗
PubMed2000

Comparison of a new neuraminidase detection assay with an enzyme immunoassay, immunofluorescence, and culture for rapid detection of influenza A and B viruses in nasal wash specimens.

The performance of a new, rapid, easy-to-perform assay based on neuraminidase enzyme activity for detection of influenza virus types A and B was compared to detection by culture, indirect immunofluorescence, and enzyme immunoassay in 479 nasal wash specimens from children with respiratory infections. Compared to isolation of influenza virus by culture, the neuraminidase assay had a sensitivity of 70.1%, specificity of 92.4%, positive predictive value of 76.3%, and negative predictive value of 89.9%. There was a higher sensitivity for the detection of influenza A virus (76.4%) than for influenza B virus (40.9%). Indirect immunofluorescence showed a sensitivity of 59.8% and specificity of 97% compared to culture isolation for detection of influenza A and B viruses. Enzyme immunoassay showed a sensitivity of 89.7% and specificity of 98.1% for the detection of influenza A alone. The quality of the nasal wash specimen had a significant effect on the detection of influenza virus by all of the assays. A strong response of the neuraminidase assay was more likely to represent a culture-confirmed influenza infection. This new rapid neuraminidase assay was useful for the detection of influenza A and B viruses in nasal wash specimens.

Fluorescent Antibody Technique, Indirect↗
PubMed2000

Computer support for collaboration in medical education.

This paper introduces I-Help, an intelligent learning environment to facilitate peer help exchanges and collaborative learning in university education. I-Help's private and public discussion areas are presented, and the agent-based pairing of suitable partners, based on student models, is illustrated.

Canada↗
PubMed1999

Chondrolipoma of the breast: a case report and review of the literature.

Chondrolipoma of the breast is a rare benign cartilage-containing mesenchymal tumor. In the case presented, a patient with a breast mass detected by physical examination was found to have a discrete nodule containing fibrolipomatous tissue with focal areas of cartilage. A review of the literature and differential diagnosis of benign mesenchymal tumors of the breast are discussed.

Breast Neoplasms↗
PubMed1998

LHRH antagonists.

After almost two decades, the research on LHRH antagonists has produced a number of decapeptides that are currently in clinical studies. The structures of these antagonists, unlike the agonists, differ substantially from that of LHRH. Five of the ten amino acids are unnatural and of D configuration. The structural combination of a hydrophobic N-terminus (residues 1, 2, and 3) and a basic/hydrophilic C-terminus (residues 6 and 8) was thought to be responsible for some HR reactions encountered with the second generation of LHRH antagonists. This side effect was greatly reduced by substituting the appropriate combination of amino acids at positions 5, 6, and 8. The next hurdle in the drug development of LHRH antagonists was solubility and aggregation. In the case of A-75998, water solubility was improved by 12- to 25-fold via substitution of NMeTyr at position 5. However, based on DLS analysis, the aqueous solutions still contained some large aggregates that were not visible to the naked eye. This formation of aggregates was eliminated on formulating A-75998 in Encapsin. In men, a single s.c. dose of 2 mg of A-75998 suppressed T to the castrate levels for over 30 hr. Other LHRH antagonists including ganirelix and cetrorelix are also in phase I/II clinical studies. Clinical studies with cetrorelix in prostate cancer; in vitro fertilization, and benign prostate hypotrophy have been reported.

Animals↗
PubMed1998

LHRH agonists.

Explore the source record for details and available documents.

Animals↗
PubMed1998

Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of the different sets of vertebrae.

Mice were generated with targeted disruptions in Hoxa7 and Hoxb7, respectively. Mice carrying the Hoxa7 mutation are healthy. No abnormalities in the formation of the skeleton or other tissues were found in these mutants. Twelve percent of Hoxb7-/- mutants show first and second rib defects similar to those observed in mice homozygous for a Hoxb9 mutation (Chen, F., Capecchi, M.R., 1997. Dev. Biol. 181, 186-196). Hoxb7-/- mice are also fertile and were used to generate double mutants with Hoxa7 to reveal potential interactions between these two paralogous genes. Mice homozygous for both mutations have first and second rib defects with higher penetrance and increased expressivity, indicating a functional role for Hoxa7 in the patterning of the upper thoracic region. Although Hoxb6, Hoxa7, Hoxb7, and Hoxb9 have distinctive anterior expression limits in axial mesoderm, the disruptions of these genes all yield first and second rib defects. A hypothesis is suggested to explain the observation that axial defects in these and other mouse Hox mutants appear to concentrate along the axial column at zones of transition between vertebral types.

Animals↗
PubMed1996

High-dose etoposide, cyclophosphamide and total body irradiation with allogeneic bone marrow transplantation for resistant acute myeloid leukemia: a study by the North American Marrow Transplant Group.

We evaluated the toxicity and efficacy of high-dose etoposide, cyclophosphamide and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) for patients with resistant, acute myeloid leukemia (AML). Between 9/84 and 11/92 we treated 70 patients with etoposide (900-1800 mg/m2), cyclophosphamide (120-180 mg/kg) and TBI (1000-1200 cGy) followed by allogeneic BMT from histocompatible siblings. Forty patients were in untreated first relapse. Median time from diagnosis to transplant was 10 months. Toxicity was similar to that observed with cyclophosphamide/TBI with the median duration of neutropenia (ANC < 500/microliters) being 19 days (range 10-27) and the median duration of thrombocytopenia being 23 days (range 13-173). Twenty-three patients remain in continuous complete remission at a median of 56 months after transplant (range 36-132 months). Probabilities of disease-free survival, persistent/recurrent disease and transplant related mortality are .32, .47, and .37 respectively. Multivariate analysis indicated that grade > or = 2 acute graft-vs-host disease and transplant in untreated first relapse were associated with increased DFS due to reduced relapse risk. We conclude that high-dose etoposide with cyclophosphamide and TBI followed by allogeneic BMT is effective therapy for resistant AML, producing durable remission in approximately one-third of those treated. Disease persistence or recurrence was the major cause of treatment failure. Further improvement in DFS following allogeneic BMT for resistant AML might be achieved by using less intensive GVHD prophylaxis or through infusion of donor peripheral blood cells in patients who fail to develop significant acute GVHD.

Acute Disease↗
PubMed1995

High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group.

Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI). We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse. With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI. Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively. DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD. Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia. We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted.

Actuarial Analysis↗
PubMed1994

In vitro and in vivo activities of reduced-size antagonists of luteinizing hormone-releasing hormone.

A novel series of octapeptide LHRH antagonists was designed on the basis of the structure of the (2-9) fragment of a LHRH agonist. By adopting a systematic SAR study, we were able to improve first the in vitro activity and then the in vivo LH suppression, raising them up to the range of the decapeptide antagonists NalGlu (51) and A-75998 (50), resulting in A-76154 (49). The octapeptide antagonist A-76154 is the most potent reduced-size LHRH antagonist reported. It suppresses LH in the castrated rat by over 80% for a period of 4 h following sc bolus administration of 30 micrograms/kg.

Amino Acid Sequence↗
PubMed1994

The use of Health Care Financing Administration data for the development of a quality improvement project on the treatment of anemia.

The Health Care Financing Administration maintains a wide array of data systems that are essential to the functioning of the Medicare program. These data, collected and maintained for the purposes of ensuring entitlements and payment for services, also can be used to monitor programmatic changes and to define potential problem areas. The end-stage renal disease (ESRD) Program Management and Medical Information System (PMMIS) is a subset of the larger Medicare statistical system. It is a historic record of all Medicare ESRD beneficiaries dating back to 1978. Basic Medicare enrollment information on ESRD beneficiaries is enhanced with the addition of information on the cause of renal failure, type of dialysis therapy, transplantation history, and cause of death. The ESRD PMMIS has been put to a number of uses in the past decade or so, ranging from basic descriptive epidemiology to analyses of mortality rates to assessments of programmatic issues such as the composite rate and dialyzer reuse. Because of the limited clinical detail in the PMMIS, there are many specific questions that cannot be adequately addressed. With approval of the Food and Drug Administration and Medicare coverage of erythropoietin, a erythropoietin monitoring system was developed to assess utilization trends of this anemia control drug. Within a few months it became evident that dosing levels for erythropoietin were much lower than expected from the clinical trials. Following a change in the payment method from a fixed amount to one based on dose level, dosing has increased markedly. However, hematocrit levels still remain below optimal levels. This lack of hematocrit response has led the Health Care Financing Administration, in concert with the renal community, to target anemia control as a potential health care quality improvement project. This paper presents an example of the type of data presentation that can be derived from the current PMMIS. The Health Standards and Quality Bureau has made a commitment to a program of continuous quality improvement. Part of this process is the provision of descriptive data that can be the starting point for an iterative approach to quality improvement.

Anemia↗