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Biomedical subjects

J J Taylor

Publications and source records attributed to J J Taylor.

At least 19 recordsLinked to original sources

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

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

Neurofibrillary tangles in experimental neurolathyrism in rats induced by imino-dipropionitrile (IDPN). 1. Fine structural changes in the spinal cord and dorsal root ganglia.

Anterior horns of the spinal cord from cervical and lumbar regions and dorsal root ganglia from these same levels were studied for ultrastructural changes in imino-dipropionitrile (IDPN) treated rats. Normal saline-injected rats, treated identically, served as controls for this study. In the spinal cord axonal balloons or dystrophic axons appeared in lightly myelinated or unmyelinated axons within 24 h after the third injection of IDPN. At this time hind leg paralysis had not yet developed. In addition to axonal changes, a few dendrites also showed neurofibrillary degeneration. Central chromatolytic changes were observed in most of the neurons, with evidence of generalized edema present within the cord. In the dorsal root ganglia axonal balloons were very prominent and showed neurofibrillary hypertrophy. Neurofibrillary material was also noted in the perikarya of medium-sized ganglion cells.

Animals

The pacemaker cell of the sinoatrial node of the rabbit.

Rabbit sinoatrial nodes were isolated and studied in an attempt to determine the cell of origin of the true pacemaker potential. Cells of the sinoatrial node of the rabbit giving rise to the characteristic true pacemaker potential were iontophoretically tagged with lanthanum. The lanthanum appeared within the cytoplasm of cells, which morpholigically are "P" cells. The lanthanum appeared as small, amorphous, electron-dense globules. It is concluded from this study that the P or pale cell is the source of the true pacemaker action potential of the sinoatrial node.

Action Potentials

Electron-microscopic study of the maturing rat red nucleus. I. The large-neuron population.

The maturing large neurons of the rat red nucleus in animals ranging in age from 1 to 21 days of postnatal life were studied ultrastructurally. Days 1--6 were characterized by rapid morphologic maturation occurring concomitantly with the onset of synaptogenesis. Morphogenesis was confined to the soma, while the first synaptic contacts were also formed in relationship to the soma. Days 6--9 demonstrated continued somal morphogenesis exemplified by cytoplasmic expansion and by the conspicuous presence of perisomatic and growth cone processes. Proximal dendritic morphogenesis was initiated, and synaptogenesis became complex with synaptic sites occurring in relation to the neuronal soma, the perisomatic processes and proximal dendrites. Days 9--15 were characterized by the completion of somal and proximal dendritic morphogenesis and by a massive degree of synaptogenic activity. During this interval, the soma lost perisomatic and growth cone processes, while somatic spines appeared. By the end of this period the neuronal soma and the proximal dendrites appeared mature in terms of both morphology and synaptic input. Complete neuronal maturation was ultimately attained by day 21 of postnatal life.

Animals

Immune complex disease. VI. Some determinants of the varieties of glomerular lesions in the chronic bovine serum albumin-rabbit system.

Glomerular lesions were evaluated by light, electron, and immunofluorescence microscopy in rabbits given daily injections, for prolonged periods of time, of either 12.5 mg. of bovine serum albumin (BSA) (group I) or increasing doses of BSA, paralleling the immune response (group II). In animals clearing 12.5 mg. or more of BSA per day (excluding those dying of anaphylaxis or unknown causes), marked differences were noted in the incidence of membranous glomerulonephritis (GLN) (50 per cent in group I versus 15.4 per cent in group II), of crescentic GLN (none in group I versus 26.9 per cent in group II), and of mesangiopathic GLN (11.1 per cent in group I versus 30.8 per cent in group II). On the basis of these variations and immunofluorescence microscopy findinds, it is concluded that the occurrence of membranous GLN is favored by the presence in the circulation of small concentrations of soluble immune complexes, whereas crescentic GLN results from the presence of high concentrations of such complexes. When BSA injections were discontinued in group I animals having membranous GLN, the immune deposits were sequestered by membranous transformation so that they were not readily solubilized by injections of large amounts of BSA; one such animal developed crescentic GLN. The observation that BSA was difficult to detect in the lesions of mesangiopathic GLN suggests that this lesion results from the deposition of complexes formed at equivalence or in antibody excess.

Animals

Ex vivo determination of potentially virulent Sporothrix schenckii,.

Hyphae from 30 isolants of Sporothrix and Ophiostoma species were washed, dried and pyrolyzed at 350 degrees C. Pyrolysis products were separated on a Carbowax column heated 7.5 degrees C/min to and maintained for 50 min at 160 degrees C. Hydrogen flame detector responses were recorded graphically. Fifteen clinical isolants of S. schenckii from geographically separated sources produced qualitatively identical pyrograms. S. foliorum, 8 avirulent S. schenckii and other Sporothrix species isolants from soils, and Sporothrix states of 6 Ophiostoma species yielded pyrograms readily distinguished from each other and from those of virulent S. schenckii. Taxonomic and clinical implications of the pyrograms are mentioned.

Ascomycota

An ultrastructural study of sympathetic ganglion satellite cells in the rat. 2. Effect of preganglionic sympathectomy.

The ultrastructure of satellite cells of the rat superior cervical ganglion was studied following preganglionic sympathectomy.Several distinct morphological alterations were observed: (a) enlargement of the intercellular space between the ganglion cells and the satellite cells, (b) dilation of the granular endoplasmic reticulum and loss of attached ribosomes, and (c) swelling of the mitochondria with disorganization of the cristae mitochondriales. The presence of degenerating nerve fibers and synaptic boutons was also noted.

Animals

Dilute ethyl alcohol: effect on the sciatic nerve of the mouse.

The histological changes produced in peripheral nerve by topical ethyl alcohol have been infrequently studied in spite of widespread use of this neurotoxic agent in the management of pain and spasticity. In the present study the sciatic nerves of a series of albino mice were exposed to ethanol in concentrations of from 10% to 50% for from 15 to 60 seconds. An immediate physiochemical reaction took place, resulting in splitting of myelin sheaths and swelling of cellular organelles and cytoplasm. Nerves subsequently underwent Wallerian degeneration. A central core of fibers appeared to be normal. The longer exposure times or higher alcohol concentrations increased the extent to which the peripheral rim of altered tissue extended centrally into the nerve. Within altered tissue, all fiber types and sizes were found to be affected to an equal degree. To study the physical properties of alcohol in solution, absolute alcohol was slowly placed at the bottom of a cylinder filled with artificial or normal human spinal fluid and sequential levels of the solution were sampled 30 and 60 seconds after injection. Though hypobaric, alcohol dispersed rapidly so that specimens taken from the bottom of the cylinder were 65% as concentrated as specimens taken from the surface.

Animals

Phlebotomy and iron deficiency.

Therapeutic and investigational phlebotomy can produce iron deficiency severe enough to warrant iron therapy or even replacement blood transfusion. This complication of modern medicine is not adequately recognized.

Anemia, Hypochromic