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Biomedical subjects

J J Taylor

Publications and source records attributed to J J Taylor.

At least 37 records · Page 2Linked to original sources

Strategies for teaching nursing research. Discovering the creative listening hole.

Creative questioning that is based on nonverbal inner listening can lead to new insights, discoveries, and perspectives. Though very challenging, the mythology of reaching the listening hole can help the student develop an ear for keys or gaps in his or her perceptions about phenomena. It can help develop respect for the rich lode of nursing experience from which researchable questions can be developed. Finally, creative research questioning introduces a new mental discipline that can lead to a fresh perception of nursing practice questions. The value of the process outweighs the risks and difficulties.

Communication↗

Characterisation of non-concordance in the T-cell receptor gamma chain genes at presentation and clinical relapse in acute lymphoblastic leukemia.

We have analysed the structure of the T-cell receptor gamma chain (TCRG) genes in a panel of biopsies taken from 24 patients with acute lymphoblastic leukemia (ALL) (13 cALL, one pre-B ALL, two null ALL and eight T-ALL) at presentation and at clinical relapse. In the majority of cases (18/24) the structure of these genes was concordant, but in a significant minority of cases (6/24) the TCRG genes were in a different conformation at different clinical stages. In three of these patients (one null ALL, two T-ALL) the clonal TCRG rearrangements detected at presentation were absent at relapse possibly as a result of clonal regression. In one other patient (cALL), the TCRG locus at relapse was rearranged to V genes which are located downstream of the V genes found in the presentation rearrangement. This indicates that the relapse leukemic clone is probably the result of clonal evolution. In two patients (one cALL, one T-ALL) there were no clonally dominant rearrangements of the TCRG genes at presentation, but evidence for clonal rearrangements at relapse, possibly as a result of clonal progression. The structure of the IgH genes were determined in four of the six patients with clonal changes in the TCRG genes and were found to be concordant. The changes in TCRG gene structure were not restricted to ALL of any one particular age group, phenotype or duration of first remission. These data indicate that the assignment of clonal specific markers based upon the sequence of TCRG rearrangements at presentation may not always be useful in the detection of minimal residual disease in ALL.

Adolescent↗

An interstitial deletion in the rearranged T-cell receptor gamma chain locus in a case of T-cell acute lymphoblastic leukaemia.

This report describes the cloning and sequencing of the breakpoint of a deletion of approximately 166 bp in the 5' region of a rearranged T-cell receptor gamma (TCRG) V gamma 2 gene from the disease cells of a patient with T-cell ALL. This abnormal rearrangement was not detected in a biopsy taken during clinical remission. Sequence analysis indicated that the deletion breakpoint occurred at a position immediately upstream of sequences found in the germline V gamma 2 gene that are closely related to known heptamer and nonamer recombination signal sequences. Furthermore, the rearrangement was found to have non-germline nucleotides (N-region) in between otherwise intact V and J segments. These data indicate that this structure may be the result of an aberrant rearrangement event in common with the frequently occurring chromosomal abnormalities found in T-cell ALL. This event could either be one directly associated with the leukaemic transformation or one occurring during normal lymphocyte development but which is coincidental with leukaemic transformation. This represents the first molecular genetic evidence for an abnormality specifically involving the TCRG locus in ALL.

Base Sequence↗

General information tapes inhibit recall of the cancer consultation.

PURPOSE: Studies of tape recordings of cancer consultations have produced conflicting results. At the same time, audiotapes containing general information about cancer are poorly evaluated and are distributed to patients in an ad hoc manner. We compared the effects of both interventions on patient satisfaction, psychologic adjustment, and recall of information following their first consultation with a medical oncologist. PATIENTS AND METHODS: Patients (n = 142) were randomized to receive (1) an audiotape of their consultation, (2) an audiotape describing cancer in general terms, or (3) no tape. Recall of information was assessed in a structured interview 4 to 20 days after the consultation. RESULTS: Satisfaction with the consultation increased linearly from no tape to general tape to consultation tape. Satisfaction with the tape itself was higher in patients who received the consultation tape (satisfaction score, 61%) compared with those who received the general tape (43%). Average recall for all groups was 6.4 of the 25 items of information presented, and 2.4 of the six points identified as particularly important by the oncologist. The consultation tape did not improve recall over the no tape control, but the general tape caused a decrease of almost two items in total recall. Spontaneous (ie, unprompted) recall was significantly poorer with the general information tape. Psychologic adjustment to cancer was unaffected. CONCLUSION: We conclude that individual audiotapes have a limited potential to increase recall of information from the oncology consultation. General information tapes about cancer appear to inhibit recall actively.

Adolescent↗

T-cell receptor heterogeneity of gamma delta T-cell clones from human female reproductive tissues.

gamma delta T cells were isolated from human decidua parietalis, decidua basalis and cervix and cloned in the presence of interleukin-2 (IL-2). T-cell receptor (TcR) expression was then analysed and compared with that of a panel of gamma delta T-cell clones from peripheral blood. Only 17/40 (42.5%) clones from decidua parietalis were V gamma 9+/V delta 2+ as compared to 68/94 (72%) of peripheral blood clones (P < 0.005). Conversely, 50% of clones from decidua parietalis but only 15% of clones from peripheral blood were V delta 1+ (P < 0.001). At least seven distinct TcR types were identified among the panel of clones from decidua parietalis and at least six different types were expressed by the panel of 17 clones from cervix. This receptor heterogeneity was not a result of interdonor variation as in all instances where more than one clone was obtained from a single sample, individual clones having between two and five receptor types were identified. However, 23/24 (95.8%) of clones from decidua basalis were V gamma 9+/V delta 2+. Most clones from decidua parietalis and cervix, whether V gamma 9+/V delta 2+ or V delta 1+, were positive for the mucosal lymphocyte marker, HML-1, but expression was often heterogeneous within a single clone. In contrast, almost all gamma delta T-cell clones from peripheral blood were HML-1-. Thus, unlike the mouse, gamma delta T cells within these human female reproductive tissues have a diverse TcR repertoire which, in decidua parietalis, is distinct from that of peripheral blood.

Antigens, Neoplasm↗

Burkitt lymphoma cell lines are prone to recombination in the switch region of the Ig mu heavy chain locus.

Different recombinations have been found at the Ig heavy chain gene loci in a number of sublines of the Burkitt lymphoma (BL) cell line Namalwa, following prolonged in vitro culture. The Namalwa sublines examined are DNA fingerprint-identical and derived from a monoclonal source. Recombinant DNA clones were used to map the Ig heavy chain gene mutations to a region between the VDJ and C mu segment of the locus. This region is associated with Ig heavy chain class switching in normal B cells. Of 24 clones established from one subline, three were found to have additional VDJ-C mu region mutations, indicating a high frequency of mutation at this locus.

B-Lymphocytes↗

Detection of T-cell receptor gamma chain V gene rearrangements using the polymerase chain reaction: application to the study of clonal disease cells in acute lymphoblastic leukemia.

This report describes the development and characterization of a method for the amplification of rearranged V-J segments of the human T-cell receptor gamma chain (TCRG) locus using an adaptation of the polymerase chain reaction (PCR) technique. The technique uses a single pair of 'consensus' primers to amplify rearrangements involving the V gamma I subgroup genes, which are common in malignant cells from acute lymphoblastic leukemia (ALL) patients. Using this method we were able to detect rearrangements in the TCRG locus in disease cells from patients with T-cell ALL (12 of 12), common ALL (10 of 14), and Null cell ALL (2 of 2) at presentation. Monoallelic and biallelic rearrangements involving V gamma I subgroup genes were identified by restriction analysis of PCR products from DNA samples from a T-cell leukemic cell line, T-cell clones, and disease cells from patients with ALL of T-and B-cell lineage at presentation. These results confirmed the presence of cell clones within the presentation samples and, in one case, confirmed the persistence of the original malignant cell clone at relapse. This is a rapid and specific method for the detection and characterization of rearrangements of the TCRG locus without recourse to Southern blotting. Therefore, the PCR technique described herein can provide the basis for the study of clonal evolution and minimal residual disease on a high proportion of patients with ALL.

Alleles↗

The molecular genetic analysis of gene rearrangements in acute lymphoblastic leukaemia.

In ALL the majority of cases possess clonal rearrangements of the Ig or TCR gene loci. Detection of these clonal markers by Southern blot analysis over a disease course has provided information on the fate and origin of leukaemic clones during treatment. Detection of these gene rearrangements has been used to detect residual disease during treatment. More recently, methods have been developed for the detection of Ig and TCR gene rearrangements using the polymerase chain reaction (PCR). This amplification technique allows for the rapid detection of gene rearrangements with a greater sensitivity than more conventional methods. The full impact and usefulness of this technique in residual disease detection has yet to be determined. The presence of the Philadelphia chromosome t(9;22) in ALL is associated with poor prognosis. Its detection by Southern blot is technically complicated due to the heterogeneity of chromosome breakpoints involved. The development of PCR-based methods for the detection of the bcr/abl mRNA associated with the Philadelphia chromosome has improved our understanding of the significance and incidence of this disease marker in ALL, emphasizing the importance of establishing Philadelphia status on all patients at diagnosis. Although longitudinal studies in CML have shown the presence of bcr/abl mRNA to be associated with residual disease, and its absence associated with long-term remission, these studies have yet to be reported for ALL. The usefulness of detection of residual disease using bcr/abl has yet to be determined.

Blotting, Southern↗

Perceptions of self and short stature: effects of two years of growth hormone treatment.

A cohort study was carried out to determine whether childrens' perception of the problem of short stature changed over 2 years of growth hormone (GH) therapy. A total of 66 children (age range, 5-15 years; mean 10.2 years) were selected on the basis of height below the 3rd centile for chronological age, height velocity below the 25th centile for bone age, prepubertal status, and absence of any organic condition causing growth failure or likely to interfere with GH action. The children were taking part in a 2-year multicentre trial to assess the effect of authentic recombinant GH on short, slowly growing children without GH deficiency (GHD). The childrens' and parents' attitudes and emotional adjustment to shortness were assessed before GH therapy commenced, and at 6 months and 2 years, using a growth-specific psychological instrument, the Attitude to Growth scale (ATG). The children were also assessed using the Piers Harris Childrens Self Concept Scale at 2 years. The mean ATG scores increased from 34.2 (95% confidence interval, 33.2-35.2) at intake to 37.2 (95% confidence interval, 36.2-38.2) at 2 years. Younger subjects had a greater increase (p less than 0.05). No sex differences occurred. Two separate factors were identified in the childrens' attitudes: emotional preoccupation with stature and a concrete focus on practical aspects. No differences were present between childrens' and parents' mean scores, though parents' estimates differed on selected items. The mean Piers Harris score at 2 years was within the normal range, and was positively correlated to the ATG but was unrelated to height. It is concluded that GH treatment may have a beneficial effect on childrens' attitudes to being short, particularly in the younger child.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Antibodies that block stimulation by TSH or TSAb of thyroid hormone secretion in primary hypothyroidism.

Antibodies that inhibit the stimulation of the thyroid by TSH have been studied in 63 patients with primary hypothyroidism of whom 34 had thyroid atrophy and 29 goitrous Hashimoto's thyroiditis. The method used measured the secretion of tri-iodothyronine (T3) from porcine thyroid slices incubated in vitro. The aims of the study were to assess the frequency and clinical correlates of blocking antibodies in an unselected series of patients, to establish their IgG nature and to examine their action in relation to the TSH receptor. Blocking antibodies were found in 25% of patients and occurred in association with both atrophic (32%) and goitrous (17%) hypothyroidism. These antibodies did not bind TSH (with one exception) nor did they inhibit binding of TSH to its receptor (also with one exception). Blocking-antibody activity was abolished by treatment of the serum with anti-hIgG or with protein A, and the activity was purified from serum by affinity chromatography on protein A sepharose-4B, thus establishing the IgG nature of the antibodies. The stimulation of T3 secretion by thyroid-stimulating antibodies was also blocked and in one case, where IgG did not block stimulation by bTSH, stimulation by hTSH was blocked. Antibodies blocking the action of TSH probably represent an important mechanism in the pathogenesis of primary hypothyroidism in some patients.

Adult↗

Prediction of remission after antithyroid drug treatment in Graves' disease.

A prospective study was carried out to determine the factors which influence response to antithyroid drug treatment in Graves' disease and to assess their predictive value. Eleven variables were included in the assessment and were subjected to discriminant analysis, log rank test and "survival" analysis. The patients were observed for a considerable period (mean duration 51 months). Carbimazole (mean total dose 8 g) was given in combination with thyroxine for an average of eight months to 72 patients. Thirty-five patients relapsed and 37 remain in remission. Thyrotrophin binding inhibiting immunoglobulins (TBII) were detectable in 74 per cent of patients at diagnosis and thyroid stimulating antibodies detectable in 70 per cent. At the end of treatment thyrotrophin binding inhibiting immunoglobulins and thyroid stimulating antibodies were present in 36 and 27 per cent of patients respectively. Levels of thyrotrophin binding inhibiting immunoglobulins were significantly higher both before and after treatment in the group who relapsed, but were not of prognostic significance in an individual patient unless the value was extremely high (TBII index greater than 70). The presence of thyroid stimulating antibodies was of no value in predicting outcome. HLA typing confirmed the known association of Graves' disease with HLA B8 and HLA DR3 but neither of these antigens conferred and increased likelihood of relapse. The likelihood of relapse is shown to be directly related to the severity of the disease at the time of diagnosis, as measured by the serum total T3, and to the size of the thyroid gland; it is not affected by age, family history of thyroid disease or ophthalmopathy. The data indicate that antithyroid drug treatment can be expected to induce long-term remission in patients with mild disease (T3 less than 5 nmol/l) and small thyroids; carbimazole at this dose level is inappropriate for patients with severe disease (T3 greater than 9 nmol/) and large goitres.

Adolescent↗

The effect of subtotal thyroidectomy with propranolol preparation on antibody activity in Graves' disease.

The effect of subtotal thyroidectomy on thyroid stimulating antibodies (TSAb), thyrotrophin binding inhibitory immunoglobulins (TBII) and antimicrosomal antibodies (MsAb) was studied in 26 patients with Graves' hyperthyroidism treated pre-operatively with propranolol, but without antithyroid drugs. Following surgery, two patients relapsed in the first year and eight patients became hypothyroid. Eighteen patients (69%) had detectable TSAb at entry and no significant change in titre was seen during propranolol therapy. Following surgery TSAb levels fell within 24 h in eight patients, and at 6 weeks only seven patients had detectable TSAb. TSAb were still detectable in seven patients at 6 months. TSAb activity did not predict the late relapses. TBII were present in 13 patients (50%) before surgery and titres remained unchanged in all but two patients during the immediate postoperative period. At 6 weeks TBII had disappeared from the serum of only three patients. During the early post-operative period TBII became transiently detectable in five of the 13 patients initially TBII negative. The two patients who subsequently relapsed remained TBII positive throughout. Microsomal antibodies were present in the sera of 22 patients (85%). Surgery was followed by a decline in titre, which was substantial in only six of 13 patients studied in detail. Thus, in 92% patients hyperthyroidism was successfully eradicated. Propranolol treatment had no effect on antibody activity. TSAb and TBII disappeared from the circulation in 61% and 46% patients, respectively. These data are compatible with the concept that lymphocytes within the thyroid are the major site of TSAb production but other important sites for synthesis of thyroidal autoantibodies probably exist. Although outcome from surgery could not be accurately predicted from TSAb or TBII status either pre- or post-operatively, the two patients who relapsed had the most severe disturbances of thyroid autoimmunity; all patients in whom initially detectable TSAb or TBII disappeared remained in remission.

Adolescent↗

Hypercalcaemia in "non-secretory" myeloma.

A patient is described with hypercalcaemia due to myelomatosis without paraproteinaemia or Bence-Jones proteinuria. Immunological investigations yielded some evidence of intra-cellular immunoglobulin production. Histological features suggested the secretion of osteoclast activating factor. Relevant experimental work in support of this interpretation is reviewed.

Bone Marrow↗

Projection systems and terminal localization of dorsal column afferents: an autoradiographic and horseradish peroxidase study in the rat.

Projection systems from the gracile nucleus and the cuneate nuclear complex to their terminal sites in the mesencephalon, diencephalon, and cerebellum were examined by means of anterograde autoradiography and retrograde horseradish peroxidase methods. Three projection systems emerge from the dorsal column nuclei, decussate via internal arcuate fibers, and form the contralateral medial lemniscus (ML). At the obex, some fibers split off the ML and course dorsolaterally, forming an ascending lateral system which fits the "lemniscal adjunct channel" (LAC) concept of Graybiel ('72). The ML continues rostrally as the "main lemniscal line channel" (MLLC). At the inferior colliculus, some LAC fibers terminate in the pontine nuclei, parabrachial, dorsal reticular nuclei, and the external and ventral medial part of the central nucleus of the inferior colliculus. More rostrally at the level of the superior colliculus, terminal fields are found in the medial nucleus of the medial geniculate body, the suprageniculate, pretectal, and mesencephalic reticular nuclei, marking the end of the LAC. In the diencephalon, gracile fibers leave the MLLC and form a crescentlike terminal field along the extreme lateral border of the ventral posterior lateral nucleus (VPL) of the thalamus. Cuneate MLLC fibers terminate in a bandlike formation in the VPL medial to the gracile termination. The third fiber system, the cuneocerebellar projection, emerges from the cuneate, the external cuneate nuclei, and the "cellular bridge" and immediately enters the ipsilateral inferior cerebellar peduncle. Upon entering the cerebellum, the major fiber component remains ipsilateral and terminates as vertical bands in vermal and paravermal lobules, and lobules I through IVa. The posterior cerebellar lobe contains terminal bands in lobules VII-IX, the copula pyramidis, and the paramedian lobule. It is concluded that the dorsolateral fiber system conforms to Graybiel's LAC. It is more divergent and probably less modality specific, whereas the medial lemniscal system conforms to the MLLC, which is said to be modality specific, less divergent, and locked to specific sensory-motor response characteristics. The topography of cerebellar terminal bands indicates that there is sensory-motor representation from all parts of the body to all parts of the cerebellum, at least in the rat.

Afferent Pathways↗

Evaluation of TBII activity in untreated Graves' disease using solubilised thyroid membranes.

The development and evaluation of a TSH radioligand receptor assay for TSH-binding-inhibiting immunoglobulins and its application to the study of patients with Graves' disease are described. Optimal conditions for the binding of 125I-TSH to solubilised thyroid membranes are defined. Polyethylene glycol precipitation was employed to prepare immunoglobulins from serum for assay and gave results comparable to ammonium sulphate precipitation. Immunoglobulins from normal serum did not interfere in the assay; preparations from patients with untreated Graves' disease gave positive results in 44 out of 56 cases. Coefficients of intra- and inter-assay variation were 7.0% and 9.8% respectively. The method is therefore not only sensitive and reproducible but is sufficiently simple and rapid for routine application.

Ammonium Sulfate↗