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Biomedical subjects

J D Richards

Publications and source records attributed to J D Richards.

At least 19 recordsLinked to original sources
PubMed2005

Antibiotic growth promoters in agriculture: history and mode of action.

This report will review the history of antibiotic growth promoter (AGP) use in the animal industry, concerns about development of antimicrobial resistance, and response in the European Union and United States to these concerns. A brief description of the history of legislation regarding feed use of antimicrobials in Denmark and the experience of animal producers following the 1998 ban will serve to illustrate the consequences on animal performance and health of withdrawing the approval for this use. The biological basis for antibiotic effects on animal growth efficiency will consider effects on intestinal microbiota and effects on the host animal and will use the germ-free animal to illustrate effects of the conventional microflora. The probability that no single compound will replace all of the functions of antimicrobial growth promoters will be considered, and methods to consolidate and analyze the enlarging database will be discussed.

Animal Feed↗
PubMed2005

Comparative in vitro and in vivo absorption of 2-hydroxy-4(methylthio) butanoic acid and methionine in the broiler chicken.

Poultry diets are typically supplemented with DL-2-hydroxy-4(methylthio) butanoic acid (HMTBA, or the hydroxy analog of methionine) or DL-methionine (DLM). Although HMTBA and DLM provide methionine activity, they are structurally distinct molecules with different physiological characteristics until they are converted to L-methionine. The relative rates of intestinal HMTBA vs. DLM absorption have been controversial, and it has been claimed that HMTBA is not fully absorbed. We measured the uptake of HMTBA and DLM in an in vitro everted intestinal slice model. Sections of intestinal slices (jejunum and ileum) were incubated with 0.1 to 50 mM HMTBA that was radiolabeled or DLM that was radiolabeled, and absorption was measured by scintillation counting. The HMTBA uptake was equal to or greater than DLM absorption in each tissue and at every time point with one exception. Furthermore, the rates of HMTBA absorption were always equal to or significantly greater than DLM uptake. In a separate in vivo experiment, absorption of HMTBA and L-methionine was monitored along the entire gastrointestinal (GI) tract. Broilers were fed commercial-type corn-soy diets supplemented with 0.21% HMTBA. Digesta was collected from crop, proventriculus, gizzard, duodenum, jejunum, ileum, large intestine, and cloaca and analyzed for the concentration of free HMTBA and free methionine in each compartment. These studies demonstrated that HMTBA is absorbed completely and along the entire GI tract, especially the upper GI tract. Furthermore, there was a higher concentration of free L-methionine than HMTBA in the digesta from every segment distal to the gizzard.

Animals↗
PubMed2005

A comparison of knee braces during walking for the treatment of osteoarthritis of the medial compartment of the knee.

In this cross-over study, we evaluated two types of knee brace commonly used in the conservative treatment of osteoarthritis of the medial compartment. Twelve patients confirmed radiologically as having unilateral osteoarthritis of the medial compartment (Larsen grade 2 to grade 4) were studied. Treatment with a simple hinged brace was compared with that using a valgus corrective brace. Knee kinematics, ground reaction forces, pain and function were assessed during walking and the Hospital for Special Surgery scores were also determined. Significant improvements in pain, function, and loading and propulsive forces were seen with the valgus brace. Treatment with a simple brace showed only significant improvements in loading forces. Our findings suggest that although both braces improved confidence and function during gait, the valgus brace showed greater benefit.

Aged↗
PubMed2003

A comparison of knee kinematic characteristics of stroke patients and age-matched healthy volunteers.

OBJECTIVE: To investigate which knee kinematic characteristics show the greatest differences between stroke patients with minimal residual disability and age-matched healthy volunteers as a first step towards the development of a sensitive, objective measure of performance of movement for use in the clinical setting. DESIGN: A comparative study. SETTING: A movement analysis laboratory. SUBJECTS: Ten patients between 6 and 12 months post stroke aged between 65 and 74 years and 10 age-matched healthy volunteers. All patients had made a good recovery and were able to complete all of the functional tasks. INTERVENTIONS: Each subject had reflective markers placed on anatomical landmarks and was filmed performing three movement tasks: sit-to-stand, walking, and step on block. MAIN OUTCOME MEASURES: Knee kinematic characteristics involving timing, joint angle and angular velocity at key points during each task. RESULTS: Significant differences were found between patients and volunteers for only some of the timing and joint angle characteristics but for all angular velocity characteristics for which the mean differences ranged from 31.85 degrees/s for sit-to-stand (p = 0.013) to 82.5 degrees/s (p = 0.014) for the swing phase of gait. CONCLUSIONS: These preliminary findings suggest that angular velocity of the knee during functional tasks might have potential as a sensitive, objective measure of performance of movement after stroke for patients with minimal residual disability.

Aged↗
PubMed2001

Yeast vectors for integration at the HO locus.

We have constructed new yeast vectors for targeted integration of desired sequences at the Saccharomyces cerevisiae HO locus. Insertion at HO has been shown to have no effect on yeast growth, and thus these integrations should be neutral. One vector contains the KanMX selectable marker, and integrants can be selected by resistance to G418. The other vector contains the hisG-URA3-hisG cassette, and integrants can be selected by uracil prototrophy. Subsequent growth on 5-FOA permits identification of colonies where recombination between the hisG tandem repeats has led to loss of the URA3 marker and return to uracil auxotrophy. We also describe several new bacterial polylinker vectors derived from pUC21 (ampicillin resistance) and pUK21 (kanamycin resistance).

Ampicillin Resistance↗
PubMed2001

Inhibition of the MEK/ERK signaling pathway blocks a subset of B cell responses to antigen.

Signal transduction initiated by B cell Ag receptor (BCR) cross-linking plays an important role in the development and activation of B cells. Therefore, considerable effort has gone into determining the biochemical signaling events initiated by the BCR and delineating which events participate in specific biological responses to Ag. We used two inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 and MEK2, PD98059, and U0126, to assess the role the Ras-mitogen-activated protein kinase pathway plays in several BCR-induced responses. PD98059 or U0126 treatment substantially inhibited the BCR-induced activation of the extracellular signal-regulated kinase (ERK) forms of mitogen-activated protein kinase in the immature B cell line WEHI-231, in immature splenic B cells, and in mature splenic B cells. However, MEK-ERK inhibition did not block BCR-induced growth arrest or apoptosis of WEHI-231 cells or apoptosis of immature splenic B cells, indicating that the MEK-ERK pathway is not required for these events. In contrast, PD98059 and U0126 treatment did inhibit the up-regulation of specific BCR-induced proteins, including the transcription factor Egr-1 in WEHI-231 and mature splenic B cells, and the CD44 adhesion molecule and CD69 activation marker in mature splenic B cells. Moreover, both inhibitors suppressed BCR-induced proliferation of mature splenic B cells, in the absence and in the presence of IL-4. Therefore, activation of the MEK-ERK pathway is necessary for a subset of B cell responses to Ag.

Animals↗
PubMed1996

Reconstitution of B cell antigen receptor-induced signaling events in a nonlymphoid cell line by expressing the Syk protein-tyrosine kinase.

B cell antigen receptor (BCR) cross-linking activates both Src family and Syk tyrosine kinases, resulting in increased cellular protein-tyrosine phosphorylation and activation of several downstream signaling enzymes. To define the role of Syk in these events, we expressed the BCR in the AtT20 mouse pituitary cell line. These nonlymphoid cells endogenously expressed the Src family kinase Fyn but not Syk. Anti-IgM stimulation of these cells failed to induce most of the signaling events that occur in B cells. BCR-expressing AtT20 transfectants were generated that also expressed Syk. Syk expression reconstituted several signaling events upon anti-IgM stimulation, including Syk phosphorylation and association with the BCR, tyrosine phosphorylation of numerous proteins including Shc, and activation of mitogen-activated protein kinase. In contrast, Syk expression did not reconstitute anti-IgM-induced inositol phosphate production. A catalytically inactive Syk mutant could associate with the BCR and become tyrosine phosphorylated but could not reconstitute downstream signaling events. Expression of the Src family kinase Lck instead of Syk also did not reconstitute signaling. Thus, wild type Syk was required to reconstitute several BCR-induced signaling events but was not sufficient to couple the BCR to the phosphoinositide signaling pathway.

Amino Acid Sequence↗
PubMed1995

Signal transduction by the B-cell antigen receptor.

The antigen receptor of B lymphocytes (BCR) plays important roles in recognition of foreign antigens and self-components to allow the immune system to make appropriate antibody responses. The BCR is a complex between membrane immunoglobulin and the Ig-alpha and Ig-beta heterodimer. Site-directed mutagenesis experiments have shown that the mu heavy chain transmembrane domain plays a key role in the association of mIgM with Ig-alpha/Ig-beta. In the absence of complex formation, mIgM is retained in the endoplasmic reticulum, and this function is also specified by the mu chain transmembrane domain. The ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta correlates well with their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. Thus, the signaling ability of the BCR appears to reside in the Ig-alpha/Ig-beta heterodimer. The cytoplasmic domains of Ig-alpha and Ig-beta each contain an ITAM sequence, which is defined by its limited homology with subunits of the T-cell antigen receptor and of Fc receptors. Moreover, chimeric proteins containing these ITAMs and surrounding sequences from the cytoplasmic domains of Ig-alpha or Ig-beta exhibit signaling function characteristics of the intact BCR. The Ig-alpha and Ig-beta chimeras are each capable of inducing all of the BCR signaling events tested and thus represent redundant functions. Cross-linking these chimeras leads to their phosphorylation and to binding of the intracellular tyrosine kinases Lyn and Syk. The BCR expressed in the nonlymphoid AtT20 cells, which express the Src-family tyrosine kinase Fyn but not Syk, was not able to trigger vigorous signaling reactions. Introduction of the active form of Syk into these cells restored some signaling events. These results are consistent with a model in which the ITAMs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases.

Animals↗
PubMed1995

Operation Desert Shield/Storm performance of soldiers enrolled in the alcohol and drug abuse prevention and control program.

This article explores the Operation Desert Shield/Storm performance of soldiers receiving predeployment treatment in the Alcohol and Drug Abuse Prevention and Control Program (ADAPCP). It describes the impact that ADAPCP soldiers' performance has on their units, both from the soldiers' and the leadership's points of view. Examination of the ADAPCP's predeployment and deployment role indicates that the ADAPCP can do more for soldiers who, while attempting to overcome substance abuse problems, face the new challenge of coping with the upheaval of deployment to a war zone. Suggestions are also made for developing an ADAPCP peace-to-war transition plan.

Adult↗
PubMed1994

Autologous bone marrow transplantation in multiple myeloma: a single centre experience of 23 patients.

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).

Adult↗
PubMed1993

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma.

In view of increasing controversy regarding the role of double hemibody irradiation (DHBI) in the treatment of multiple myeloma, we have analysed the use of this technique at our institution over a 6-year period. Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemoresistant to initial therapy. Fifteen patients received alpha IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week, as part of a randomized trial. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. alpha IFN did not appear to prolong survival (OS or PFS) post-DHBI. Cytopenia was a significant problem, such that only 60% of patients had counts adequate enough to be eligible for alpha IFN. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The use of radioisotopes in haematology.

Radioisotopes used in haematology may be divided into four groups: 1. those used for in vivo studies, involving the labelling of cells in the blood or bone marrow and the use of labelled plasma albumin; 2. investigations involving surface counting over organs such as the bone marrow, spleen, liver and heart; 3. in vitro use of radioisotopes in the haematology laboratory and 4. isotopes used as part of imaging procedures. The shorter the half life of the isotope, the more limited patient exposure to radioactivity will be, but the greater the problems of starting and completing the investigation before the isotope has decayed. Isotopes studies should not be carried out in children or pregnancy unless there are exceptional clinical indications.

Absorption↗
PubMed1992

Prospective randomised study of double hemi-body irradiation with and without subsequent maintenance recombinant alpha 2b interferon on survival in patients with relapsed multiple myeloma.

Immediately before first hemi-body irradiation, 59 patients with relapsed multiple myeloma were randomised to receive or not to receive subsequent alpha-2b interferon maintenance. 13 patients (22%) [8 of 31 (26%) controls, 5 of 28 (18%) in the interferon arm] received single hemi-body irradiation alone due to progressive disease and/or persistent cytopoenias following the initial procedure. Mean time between upper and lower hemi-body irradiation was 69 days (range 35-294). Of 23 patients randomised to receive interferon and completing double hemi-body irradiation, 15 (65%) achieved peripheral blood counts adequate to allow interferon administration as per study criteria commencing at a mean 116 days (61-241) from time of study entry. The mean period of interferon therapy, starting at a mean 65 days (26-160) post second hemi-body irradiation, is 16.4 months (2-33.5). There was no significant difference in median survival durations (10 months) from time of initial radiotherapy between control and interferon patients.

Aged↗
PubMed1992

Mini-BEAM followed by BEAM and ABMT for very poor risk Hodgkin's disease.

High dose chemotherapy and autologous bone marrow transplantation (ABMT) is an effective form of salvage therapy in patients with relapsed or resistant Hodgkin's disease. Patients with large tumour masses at the time of ABMT have a poorer prognosis and we have therefore administered intermediate dose BCNU, etoposide, cytarabine and melphalan (mini-BEAM) prior to high dose therapy with the same agents (BEAM) and ABMT in such patients. In addition we have used the same strategy in patients with bone marrow infiltration at the time of relapse in an attempt to clear the bone marrow for transplant. A total of 23 patients received mini-BEAM and 21 proceeded to BEAM and ABMT. Platelet engraftment was delayed compared to BEAM recipients who had not received mini-BEAM (P = 0.008) but there was only one procedure related death. Responses to BEAM and ABMT were not predicted by the response to mini-BEAM indicating a dose response effect at the upper end of the dose intensity spectrum. At 2 years, the overall survival and progression free survival are 61% and 46% respectively for this group of Hodgkin's patients with extremely poor prognosis.

Adult↗
PubMed1992

Granulocytic sarcomas of small intestine and brain are associated with acute myelomonocytic leukaemia with abnormal eosinophils and inversion of chromosome 16.

We report two cases of acute myelomonocytic leukaemia with abnormal eosinophils (M4Eo) in which the presenting feature was small bowel obstruction. We suggest there is a unique clinicopathological association between small intestine involvement with leukaemia and the M4Eo subtype. Central nervous system involvement by myeloblastoma occurred in one of the two cases which is a recognised feature of M4Eo and should necessitate prophylaxis with intrathecal therapy. Inversion of chromosome 16 which is a cytogenetic marker for M4Eo was demonstrable in one of the two cases.

Biomarkers, Tumor↗