PubMed Health⌕ Search

Biomedical subjects

A Harwood

Publications and source records attributed to A Harwood.

At least 19 recordsLinked to original sources
PubMed1999

A myb-related protein required for culmination in Dictyostelium.

The avian retroviral v-myb gene and its cellular homologues throughout the animal and plant kingdoms contain a conserved DNA binding domain. We have isolated an insertional mutant of Dictyostelium unable to switch from slug migration to fruiting body formation i.e. unable to culminate. The gene that is disrupted, mybC, codes for a protein with a myb-like domain that is recognized by an antibody against the v-myb repeat domain. During development of myb+ cells, mybC is expressed only in prestalk cells. When developed together with wild-type cells mybC- cells are able to form both spores and stalk cells very efficiently. Their developmental defect is also bypassed by overexpressing cAMP-dependent protein kinase. However even when their defect is bypassed, mybC null slugs and culminates produce little if any of the intercellular signalling peptides SDF-1 and SDF-2 that are believed to be released by prestalk cells at culmination. We propose that the mybC gene product is required for an intercellular signaling process controlling maturation of stalk cells and spores and that SDF-1 and/or SDF-2 may be implicated in this process.

Amino Acid Sequence↗
PubMed1994

Tyrosine kinase and CD45 tyrosine phosphatase activity mediate p21ras activation in B cells stimulated through the antigen receptor.

Cross-linking of the Ag receptor (AgR) induces intracellular signaling events in B cells, such as p21ras activation, that lead to their proliferation and differentiation. This event is accompanied by the tyrosine phosphorylation of the p21ras-associated GTPase-activating protein p120 ras.GAP, raising the possibility that AgR-stimulated p21ras activity is regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases) in B cells. To test this possibility, we examined the effects of PTK and PTPase inhibitors on protein tyrosine phosphorylation and p21ras activation induced by AgR cross-linking in TNP-specific TA3 7.9 murine B lymphoma cells. Although AgR-induced protein tyrosine phosphorylation was inhibited by the PTK inhibitors genistein and herbimycin A, it was enhanced by exposure to the PTPase inhibitor phenylarsine oxide (PAO). Cross-linking of the AgR by Ag or F(ab')2 anti-IgM induced a rapid (within 5 min) two- to threefold increase in p21ras activation in 7.9 B cells. Interestingly, a second peak of p21ras activation was evident at approximately 40 min after stimulation. Genistein and herbimycin A and PAO each blocked AgR-stimulated p21ras activation. Similarly, Ag-induced p21ras activation was inhibited by pretreatment of 7.9 B cells with an anti-CD45 mAb (detects the 220-kDa B cell isoform of CD45). Moreover, p21ras activation was induced by Ag and F(ab')2 anti-IgM in CD45+ but not CD45- J558L microns 3 B cells. These data indicate that p21ras activation induced by AgR cross-linking in B cells is regulated by both PTK and CD45 PTPase activities.

Animals↗
PubMed1993

Comrades.

Four organisations have collaborated to produce a consensus statement on clinical management. The result, writes Alys Harwood, could lead to a revolution in patient care.

Decision Making, Organizational↗
PubMed1993

Interacting signalling pathways regulating prestalk cell differentiation and movement during the morphogenesis of Dictyostelium.

Analysis of the expression patterns of two genes encoding extracellular matrix proteins shows there to be an unexpectedly complex pattern of prestalk cell differentiation and movement during the morphogenesis of Dictyostelium. The organism employs both cell sorting and positional differentiation to generate a patterned structure but these two mechanisms are used at different times during development. During slug formation prestalk cells arise at scattered positions within the aggregate and then move to its apex to form the tip. In contrast, during culmination, stalk cell differentiation occurs in a positionally localized manner at the entrance to the stalk tube. Two interacting signalling pathways regulate the differentiation of prestalk and stalk cells. Prestalk cell differentiation is induced by DIF, a chlorinated hexaphenone, and a repression mechanism prevents DIF acting to induce premature stalk cell differentiation during slug migration. At culmination intracellular cAMP levels rise, the cAMP dependent protein kinase (PKA) is activated and the block to stalk cell differentiation is lifted. Activation of PKA is also necessary in order that prestalk cells move to the entrance of the stalk tube at culmination. Thus, in Dictyostelium, PKA plays a role both in the regulation of cellular differentiation and in morphogenetic cell movement.

Animals↗
PubMed1992

A simple method of generating axenic derivatives of Dictyostelium strains.

We describe a generally applicable method of adapting Dictyostelium from growth on a bacterial food source to axenic growth. Cells are initially selected by growth on a plastic substratum but subsequently acquire the ability to grow in suspension culture. These strains can be transformed efficiently by DNA-mediated gene transfer.

Animals↗
PubMed1991

Failure of peripheral arterial balloon angioplasty: does platelet deposition play a role?

The pathophysiological response to peripheral percutaneous transluminal balloon angioplasty in 20 patients was investigated using 111-Indium labelled platelets. Platelet deposition was quantified by measuring the degree of radioactivity uptake at angioplasty and control sites using a computer linked system and expressing the uptake as a ratio of angioplasty/control. Following platelet labelling, scans were performed before angioplasty and at 1, 24 and 48 h after angioplasty. To assess patency of the angioplasty, ankle brachial Doppler pressure indices were performed and supported by repeat angiograms if doubt of patency existed. All patients were followed-up at 1 week, 1 month and 6 months to correlate the degree of early platelet uptake with failure. The mean +/- sem platelet radioactivity ratio at the angioplasty site increased from 1.1 +/- 0.1 prior to the procedure to a peak of 2.1 +/- 0.3 at 1 h (p less than 0.01), 1.6 +/- 0.2 at 24 h (p less than 0.05), and 1.7 +/- 0.3 at 48 h (p less than 0.05). Angioplasties that failed within 6 months tended to have a higher maximum early platelet uptake (3.1 +/- 0.6) compared to successful angioplasties (1.9 +/- 0.3) but the difference was not significant in the numbers studied. This study provides a suitable model to assess the role of platelet accumulation in angioplasty failure and the influence of various antiplatelet regimes.

Adult↗
PubMed1989

Optimization and in situ detection of Escherichia coli beta-galactosidase gene expression in Dictyostelium discoideum.

We show that a fusion gene, containing the promoter and 5'-noncoding region of a Dictyostelium discoideum actin 6 gene linked to the Escherichia coli beta-galactosidase (beta Gal) gene (lacZ), directs the production of functionally active beta Gal in D. discoideum and that the enzyme can be detected by staining in situ; a procedure which will be of great value in analyzing cell-type-specific gene expression. We illustrate this by fusing lacZ to the promoter of the prespore-specific gene, D19, and localizing expressing cells in migrating slugs. Optimal expression requires the inclusion of termination and polyadenylylation signals and we describe pDDlac, a vector containing a multiple cloning site upstream from a lacZ-Dictyostelium terminator fusion, which can be used to analyze regulated promoters.

Amino Acid Sequence↗
PubMed1987

Carcinoma of the subglottis. Results of initial radical radiation.

During the 12-year period 1971 to 1982, 23 patients with primary squamous cell carcinoma of the subglottis were treated with initial radical radiation therapy. There were 19 men and four women, with a mean age of 64 years. Five patients had T1 tumors, four had T2, three had T3, and 11 had T4. The actuarial overall and cause-specific survival rates were 26% and 61%, respectively. Local control was achieved with initial radiation therapy in 16 patients (70%). Subsequent local control was achieved in one other patient following surgery for recurrence, giving an ultimate local control figure of 74% (17 of 23 patients). All patients with T1, T2, and T3 disease achieved local control with initial treatment; however, seven of the 11 patients with T4 disease either had residual disease following radiation therapy or developed local recurrence on follow-up.

Aged↗
PubMed1985

Radiation effects on the external auditory canal.

Radiation is used to treat many head and neck tumors, and of necessity the temporal bone is sometimes included in the paths of radiation. We studied the histopathology of the external auditory canal in 13 temporal bones from 10 patients who had undergone irradiation for head and neck tumors. The pathologic changes noted could be divided into: bony changes, and soft tissue changes. Bony changes manifested were those of resorption, fibrosis, empty lacunae, and sequestration. There were five soft tissue changes: the formation of a secondary cholesteatoma, ulceration of the lining epithelium with resorption of the underlying bone, thickened epithelium in the canal as well as in the tympanic membrane, subepithelial fibrosis, and atrophic ceruminous glands. Clinically these changes can be manifested as a persistent otitis externa, with otorrhea and otalgia.

Adult↗
PubMed1984

Results and toxicity of the treatment of anal canal carcinoma by radiation therapy or radiation therapy and chemotherapy.

The results of treating anal canal carcinoma by radical external beam radiation alone (RT) or by combined 5-fluorouracil, mitomycin C and radiation (FUMIR), were compared in nonrandomized groups of patients treated in a single center. In each treatment regimen, surgery was reserved for those patients with residual carcinoma. The uncorrected 5-year survival rate in each group was approximately 70%, but primary tumor control was achieved in 93% (28/30) with FUMIR compared to 60% (15/25) treated with RT. Acute hematologic and enterocolic toxicity with uninterrupted external beam radiation courses of 5000 cGy in 4 weeks plus chemotherapy led to the adoption of split-course treatment. Serious late toxicity requiring surgical intervention occurred in 3 of 25 following RT, and in 5 of 30 following FUMIR. Colostomies were needed as part of treatment for residual carcinoma or for the management of treatment-related toxicity in 11 of 25 treated by RT and have been required to date in 4 of 30 treated by FUMIR. The improvement in the primary tumor control rate and the reduction in the number of patients requiring colostomy when compared with the results of RT favor combined chemotherapy and radiation as the initial treatment for anal canal carcinoma.

Actuarial Analysis↗
PubMed1984

On sudden death.

Explore the source record for details and available documents.

Death, Sudden↗
PubMed1984

Primary radiation therapy for juvenile nasopharyngeal angiofibroma.

Evidence is presented of the effectiveness and relative lack of serious toxicity of external beam megavoltage radiation therapy (RT) as primary treatment for juvenile nasopharyngeal angiofibroma. The importance of careful radiological evaluation of tumor extent prior to irradiation is stressed, and only moderate dose RT is required. Fifty-five patients have been treated by RT and followed for from 3 to 26 years. Forty-four of 55 patients (80%) had permanent tumor control following a single course of 3000 cGy to 3500 cGy over 3 weeks. Surgical resection or a second course of RT controlled the tumor in all 11 patients in whom regrowth occurred. Angiofibromas involute slowly after RT so that 50% of patients still had visible masses in the nasopharynx 12 months after treatment, but only 10% had any visible abnormality 36 months after RT. Retreatment was necessary only if symptoms recurred, and continued follow-up showed that most asymptomatic nasopharyngeal masses resolved completely. Acute and late toxicity rates were low. Two patients developed tumors in the head or neck following RT. There was no significant clinical impairment of growth or endocrine function. A single course of external beam megavoltage radiation to 3000 cGy in 3 weeks is an effective first treatment for patients with juvenile nasopharyngeal angiofibroma.

Adolescent↗
PubMed1982

Appearance of a partial nephrogram with an absent kidney.

A case is reported of a 16-year-old female who sustained a gunshot wound to the left upper abdomen. Early opacification of a structure in the left upper quadrant on an excretory urogram was suggestive of a nephrogram. The left kidney was absent at operation. The diagnostic limitations of excretory urography in the trauma patient and the alternative diagnostic techniques, radionuclide scanning, arteriography, or tomography, or possibly operative intervention, are recommended. Although not found in our patients, a thorough search for an ectopic kidney should be made.

Abdominal Injuries↗
PubMed1977

Puerto Rican spiritism. Part I--Description and analysis of an alternative psychotherapeutic approach.

Spiritism is a multifunctional institution which serves in the Puerto Rican community as a religion, a voluntary organization, a way of ordering social relationships, a source of personal identity, and a form of psychotherapy. This paper, based on participant observation in 79 Puerto Rican households and 6 spiritist centros in a low-income area of New York City, describes this institution and examines its contributions to a broader understanding of psychological healing as well as its practical implications for community health. In discussing spiritist psychotherapy, the paper outlines the conditions which lead clients to consult spiritists and examines its system of diagnosis and treatment. A comparison of the therapeutic goals of spiritism and mainstream psychiatric therapies reveals fundamental premises in both that provide the symbolic means by which certain behaviors may be bracketed off and rendered ego-alien for clients. While spiritism distances the client from unwanted behavior by attributing it to intrusive spirits and then removing the spirits, many psychiatric therapies accomplish distancing by attributing behavior to remote social causes which are then relearned or 'worked through'. What spiritism accomplishes symbolically by removal in space, psychiatric therapies handle through removal in time. The practical import of spiritist psychotherapy for community health is examined under the following rubrics: (1) spiritism as a treatment of choice, (2) implications of spiritist procedures for psychiatric treatment, and (3) interrelations between spiritists and community health programs.

Cultural Characteristics↗