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Biomedical subjects

K E Jones

Publications and source records attributed to K E Jones.

At least 37 records · Page 2Linked to original sources
PubMed1996

An alternative splice variant of the mouse TRH receptor mRNA is the major form expressed in the mouse pituitary gland.

The sequences of the mouse and rat TRH receptors (TRH-Rs) show 94% similarity at the protein level. However, they differ significantly at their carboxy terminals, i.e. the mouse TRH-R ends with an asparagine at position 393 while, in the rat, residue 393 is lysine and an additional 19 amino acids are added before the first stop codon. In the mouse cDNA, the sequence encoding these additional amino acids is located 224 bp downstream in the 3' untranslated region (3'UT). As the mouse TRH-R was cloned from thyrotrope-derived TtT97 tissue and the rat TRH-R from lactotrope-derived GH cell lines, we have investigated whether this difference at the carboxy terminus represents a species-specific or cell type-specific pattern of TRH-R expression. Total RNA was isolated from mouse pituitary and TtT97 tissue, and rat pituitary and GH3 cells. Reverse transcription PCR analysis was performed using primers that would generate DNA fragments including the stop codon in either the mouse or the rat TRH-R and, in the mouse form, the extra 224 bp of 3'UT. This would generate a product of 234 bp from the rat sequence and 441 bp from the mouse sequence. In rat pituitary and GH3 cDNA, PCR generated the expected 234 bp product but not a band representing the mouse sequence. In both mouse pituitary and TtT97 cDNA, neither the expected 441 bp nor the 234 bp fragments were amplified; instead a larger, 829 bp, product was generated. Sequence analysis revealed a 388 bp insertion at position 1663 in the 3'UT compared with the published mouse TRH-R sequence. Ribonuclease protection analysis using this 829 bp fragment as a probe showed that this sequence represented the major TRH-R mRNA species in mouse pituitary and TtT97 RNA. A genomic clone containing this region of the mouse TRH-R gene was isolated and analysis of the sequence in this region revealed that this longer form of the mouse TRH-R could be generated by alternative splicing. In summary, we have shown that the carboxyterminal differences between the mouse and rat TRH-Rs are species-specific rather than cell type-specific, and that the major TRH-R mRNA expressed in mouse pituitary contains an additional 388 bp of 3'UT compared with the published sequence. As a region in the 3'UT of the published mTRH-R sequence has been shown to be important for stability of this mRNA, this additional 3'UT sequence could have major effects on the regulation and stability of the mouse TRH-R mRNA.

Alternative Splicing↗
PubMed1996

Comparison of peripheral Ia and corticomotoneuronal composite EPSPs in human motoneurons.

The effects of excitatory inputs arising from Ia afferent and corticomotoneuronal volleys on repetitively firing flexor carpi radialis (FCR) motoneurons were compared in normal human subjects. Peripheral (Ia) volleys were produced by transcutaneous electrical stimulation of the median nerve and by mechanical taps to the FCR tendon. Transcranial magnetic stimulation (TMS) was used to activate the corticomotoneuronal pathway. The duration of the excitatory response peaks measured from peri-stimulus time histograms (PSTHs) and the time course of the response trajectories were both taken to reflect the shapes of the underlying composite excitatory postsynaptic potentials (EPSP)s acting upon that motoneuron. The duration of excitatory response peaks for the H-reflex and the first sub-peak (SP1) of the motor unit's response to TMS were similar and were typically less than those arising from tendon taps. The response trajectories, which measure the excitability of the motoneuron during different phases of the afterhyperpolarization, overlapped for H-reflex and SP1 responses, but were different for tendon tap inputs. Our results indicate that the SP1 response of a motoneuron to TMS input and its response to near-synchronous Ia afferent activation are mediated by composite EPSPs with similar rise times. We suggest that a similar spatial distribution of synaptic boutons for both Ia and corticomotoneuronal input to motoneurons innervating FCR is likely.

Adult↗
PubMed1995

Survey of health promotion organisational arrangements and levels of service for health promotion.

This study was promoted by the Executive Committee of the Association of Directors of Public Health when faced with the need to examine the organisation of and quantify health promotion arrangements in the Health Districts of England and Wales, resulting from the concerns of many of the members of the Association. These concerns were based on the views that health promotion is a key purchasing function of the District Health Authorities and must be appropriately and effectively structured and adequately resourced if the requirements of The Health of The Nation are to be fulfilled. There are many aspects to health promotion work and the delivery of health promotion services which will need addressing in the new commissioning environment of the NHS. A need was recognised for up-to-date data about health promotion services to inform a necessary debate about future arrangements, since it appeared that organisational change was being driven by influences unconnected with the possibly most appropriate structure of health promotion departments and which relate to a contemporary view of health promotion. Reducing the size and cutting the cost of commissioning authorities was perceived as one of the most important influences. A postal questionnaire survey to all Health District and Regional Health Authorities in England and Wales was conducted covering questions about the present organisational arrangements and levels of service, and soliciting the opinions of those canvassed. A total of 185 District and Regional Health Authorities, effectively reduced to 171 because of mergers, was sent questionnaires, of which 141 were completed and returned, giving a response rate of 82.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Contract Services↗
PubMed1995

Responses of human motoneurons to Ia inputs: effects of background firing rate.

The effects of synchronous Ia volleys on the firing probability of repetitively firing human motoneurons were examined at fast and slow firing rates. Ia afferents of either the median or the posterior tibial nerve were stimulated, while single motor unit activity was recorded from the homonymous muscles. Motoneuron responses to the Ia inputs were quantified by measurement of the magnitude of the short latency excitatory peak in peristimulus time histograms (PSTHs). When the stimuli were given at random with respect to the times of motor unit spikes, the magnitude of the PSTH peak (response probability) was significantly lower at a faster firing rate. In the "triggered" mode of stimulation, stimuli were given at various known times during the interspike interval. In this mode the response probability to the input increased monotonically as the stimuli were delivered progressively later during the interspike interval. The response probability at a fixed delay with respect to the triggering spike was higher at the faster firing rate. The results obtained with the two modes of stimulation are not in contradiction and both may be explained by the nature of membrane voltage trajectories and ionic conductances during the interspike interval described for repetitively firing cat motoneurons.

Adult↗
PubMed1994

Recruitment order of motoneurons during functional tasks.

The recruitment order of motoneurons of first dorsal interosseous (1DI) muscle has been shown to be the same during either isometric abduction or flexion of the index finger. However, it is not known whether this stereotyped recruitment is the same for all functional tasks. This question was addressed by using the 1DI muscle, which contributes to many functional tasks involving the hand and fingers. Single motor units and surface electromyographic activity were recorded from 1DI in three human subjects. Each subject performed tasks of abduction of the index finger, rotation to unscrew a threaded knob and pincer to close a spring-loaded clip. The same motor units were activated for each of the three tasks, providing no evidence for the existence of task groups. The order of recruitment of pairs of selected motor units was the same for each of the three tasks.

Adult↗
PubMed1994

Evidence that phosphorylation events participate in thyroid hormone action.

Using both a protein phosphatase inhibitor, okadaic acid (OA), and a protein kinase inhibitor, H7, to modify phosphorylation events in the cell, we investigated the effects of these agents on transcriptional activation via exogenous rat thyroid hormone receptor (TR) isoforms in transiently transfected cells and endogenous TRs. CV-1 cells were transiently cotransfected with expression plasmids encoding either the rat TR alpha 1 or TR beta 1, and luciferase reporter plasmids containing either the synthetic DR4 or the chick lysozyme F2 thyroid hormone response elements (TREs). For both receptor isoforms, there was an enhancement of transcriptional activity after incubation with 5 nM T3 for 24 h compared to hypothyroid levels. There was little change in transcriptional activation in the presence of 25 nM OA alone; however, for both TR isoforms and both TREs studied, OA augmented the stimulatory effects of T3. For the F2 TRE, transcriptional activation via TR alpha 1 increased from 19- to 35-fold, and that via TR beta 1 increased from 6- to 10-fold in the presence of T3 and OA compared to that with T3 alone. Similar results were found for the DR4 TRE. OA enhanced transcriptional activation by T3 in a dose-dependent manner. Increasing concentrations of OA (0, 5, 25, and 50 nM) further increased relative luciferase activity from 11-fold in the absence of OA to 45-fold in the presence of 50 nM OA. The protein kinase inhibitor, H7, caused no change in the transcriptional activity of the reporter plasmids via TR alpha 1 in the absence of T3, but completely blocked transcriptional activation by T3 for both the DR4 and the F2 TREs. H7 also blocked stimulation of endogenous GH and inhibition of endogenous TR beta 2 mRNAs by T3 in GH3 cells. These results indicate that phosphorylation events in the cell play an important role in transcriptional activation via both TR isoforms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Increase in c-erbA alpha 2 mRNA in the parvocellular region of the paraventricular nucleus of the hypothalamus following thyroidectomy in the adult male rat.

To examine thyroid hormone regulation of c-erbA alpha 2 mRNA expression in the parvo-cellular region of the paraventricular nucleus of the rat hypothalamus (pPVN), quantitative in situ hybridization was performed using 3H-labeled probe complementary to c-erbA alpha 2 mRNA. Thyroidectomy induced a significant increase in the number of silver grains overlying the cytoplasm in the pPVN relative to sham-operated controls. This effect was prevented by daily injection of thyroxine. These results indicate that hypothyroidism induced an increase in cellular c-erbA alpha 2 mRNA level in the pPVN.

Animals↗
PubMed1993

Recruitment of motor units in human flexor carpi ulnaris.

In 1949, Denny-Brown reported that the motoneuron pool of the human flexor carpi ulnaris (FCU) muscle was fractionated into subpopulations, each subpopulation being activated during a different voluntary motor task. The following report presents data on motor unit recruitment in the human FCU muscle for the tasks of isometric flexion and ulnar deviation, cocontraction of the forearm muscles and non-isometric flexion of the wrist. These observations show that every FCU motor unit tested reliably, contributed to all four tasks, that is, no separate subpopulations were observed for any of the contractions tested. Furthermore, the order of recruitment was the same for all four tasks.

Action Potentials↗
PubMed1993

Regulation of thyroid hormone receptor beta-2 mRNA levels by retinoic acid.

The thyroid hormone receptor, TR beta-2, whose expression is limited to the pituitary and parts of the central nervous system, is strongly negatively regulated at the pre-translational level by thyroid hormone (T3). We have investigated whether retinoic acid (RA), whose receptors (RARs) share a high degree of homology with the thyroid hormone receptors (TRs), can regulate this gene in a manner similar to T3, as has been shown for the growth hormone (GH) gene. GH3 cells were incubated with 10 nM T3, 1 microM RA or both for 48 h and then TR beta-2 mRNA levels determined by RNA blot hybridization analysis. We observed a 73% decrease in TR beta-2 mRNA levels after incubation with T3 and a two-fold increase in TR beta-2 mRNA levels after incubation with RA alone. In the presence of RA, the T3 effect on TR beta-2 mRNA levels was blunted with mRNA levels decreasing by only 20%. We investigated the mechanism by which retinoic acid increases and opposes the effects of T3 on levels of TR beta-2 mRNA. In transient transfection experiments using a reporter plasmid containing the TR beta-2 promoter and in nuclear run on assays, we found no effect of RA on TR beta-2 gene transcription. We then investigated whether the effects of RA were mediated at the post-transcriptional level. Determination of the apparent half-life of TR beta-2 mRNA using the transcriptional inhibitor, actinomycin D, showed that RA had no effect on TR beta-2 mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Survey of the opinions of general practitioners about health services in a rural setting.

OBJECTIVES: Using a tested survey protocol, to obtain under comparable circumstances the opinions and subjective assessments of general practitioners regarding health care services in a contrasting rural health district, to obtain indications of those services which, by reason of the opinions of general practitioners in relation to their quantity and quality, might benefit from further enquiry or even detailed assessment and, as in the previous survey, to facilitate the close working with general practitioners without which population based needs assessment and further enquiry and research into the development of healthcare services will be handicapped. DESIGN: A postal questionnaire survey of all general practitioners in the health district. SETTING: North Lincolnshire health district. SUBJECTS: One hundred and forty eight general practitioners, of whom 104 responded, two by letter only. MAIN OUTCOME MEASURES: Scores of quantity and of quality for 24 hospital services and 32 community services. The frequency with which services were identified as a priority for improvement, and written comments about the services surveyed. RESULTS: Most services were thought by general practitioners to be adequate or better in both quantity and quality, involving a surprising degree of agreement. In only six of the 56 services were these considered by more than 50% of the doctors responding to be inadequate or grossly inadequate in quantity, and in only eight services were these found by more than 15% of doctors to be poor or very poor in quality. Complaints about quantity of service were more frequent than complaints about quality of service, and community services received more complaints from general practitioners about both quality and quantity than the hospital services. The services most general practitioners wanted improved were orthopaedics, psychiatry, physiotherapy and chiropody. CONCLUSIONS: This survey confirmed the suitability of the postal questionnaire for assessing the impressions of general practitioners about both the quantity and quality of services available in their support. Consistent agreement between general practitioners about the services surveyed parallel a comparable survey undertaken in a largely urban area, showing close similarities with the results of this survey with only relatively minor local variations. The results provide pointers for health needs assessment of key services.

Attitude of Health Personnel↗
PubMed1992

A glass/silicon composite intracortical electrode array.

A new manufacturing technique has been developed for creating silicon-based, penetrating electrode arrays intended for implantation into cerebral cortex. The arrays consist of a 4.2 mm x 4.2 mm glass/silicon composite base, from which project 100 silicon needle-type electrodes in a 10 x 10 array. Each needle is approximately 1,500 microns long, 80 microns in diameter at the base, and tapers to a sharp point at the metalized tip. The technique used to manufacture these arrays differs from our previous method in that a glass dielectric, rather than a p-n-p junction, provides electrical isolation between the individual electrodes in the array. The new electrode arrays exhibit superior electrical properties to those described previously. We have measured interelectrode impedances of at least 10(13) omega, and interelectrode capacitances of approximately 50 fF for the new arrays. In this paper, we describe the manufacturing techniques used to create the arrays, focusing on the dielectric isolation technique, and discuss the electrical and mechanical characteristics of these arrays.

Electric Conductivity↗
PubMed1992

Molecular cloning of a complementary deoxyribonucleic acid encoding the thyrotropin-releasing hormone receptor and regulation of its messenger ribonucleic acid in rat GH cells.

Rat pituitary GH cells have been used extensively to study the biochemical actions of TRH on lactotropic cells. To investigate the structure and regulation of the rat TRH receptor (rTRHR), we have cloned its cDNA from GH4C1 cells. Using the polymerase chain reaction with degenerate primers and pools of cloned cDNAs from a GH4C1 cDNA library, a fragment sharing high similarity to the mouse thyrotrope TRHR (mTRHR) was identified. Conventional library screening with this fragment was used to isolate a single cDNA. mRNA synthesized in vitro from this cDNA was injected into Xenopus oocytes, and a characteristic conductance response to TRH was detected by voltage clamp recording. DNA sequence analysis revealed a molecule of 412 amino acid residues, with 96% similarity to the mTRHR. However, in contrast to the mTRHR, the rTRHR had an additional 19 amino acid residues at its carboxy-terminus. A mRNA of about 4 kilobases was identified in GH3 cells. Regulation of the rTRHR mRNA concentration was studied in GH3 cells. Steady state rTRHR mRNA levels were decreased to 30% of the control level by incubation with TRH for 48 h and increased 4-fold by incubation with dexamethasone for 12 h. Southern blot analysis of genomic DNA from GH3 cells gave a simple banding pattern consistent with a single copy gene. We conclude that the rTRHR shares high primary sequence similarity to the mTRHR, but the rTRHR has an extension of 19 amino acids at its carboxy-terminus, which is lacking in the mTRHR.

Amino Acid Sequence↗
PubMed1991

A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array.

A method has been developed for the manufacture of a "three-dimensional" electrode array geometry for chronic intracortical stimulation. This silicon based array consists of a 4.2 x 4.2 x 0.12 mm thick monocrystalline substrate, from which project 100 conductive, silicon needles sharpened to facilitate cortical penetration. Each needle is electrically isolated from the other needles, and is about 0.09 mm thick at its base and 1.5 mm long. The sharpened end of each needle is coated with platinum to facilitate charge transfer into neural tissue. The following manufacturing processes were used to create this array. 1) Thermomigration of 100 aluminum pads through an n-type silicon block. This creates trails of highly conductive p+ silicon isolated from each other by opposing pn junctions. 2) A combination of mechanical and chemical micromachining which creates individual penetrating needles of the p+ silicon trails. 3) Metal deposition to create active electrode areas and electrical contact pads. 4) Array encapsulation with polyimide. The geometrical, mechanical, and electrical properties of these arrays should make them well suited as interfaces to cortical tissue.

Animals↗
PubMed1991

Deterioration in blood glucose control in females with diabetes changed to a basal-bolus regimen using a pen-injector.

Although the basal-bolus regimen of insulin delivery is more physiological than conventional twice daily insulin it does not usually improve blood glucose control. Having recently withdrawn 3 patients from pen-injector therapy for deteriorated blood glucose control we examined the records of all our diabetic patients on a pen-injector for at least 1 year. Of the 51 patients identified, 3 had died, 2 moved away, and 4 patients (3 females) had pen-injector therapy withdrawn for poor control; 3 patients had inadequate records. The remaining 21 males and 18 females were well matched for age, duration of diabetes, and duration of pen-injector treatment. Blood glucose control deteriorated significantly during pen-injector therapy in female patients (9.6 +/- 1.2 to 10.7 +/- 1.4%, p = 0.02), but not in the males (9.3 +/- 1.3 vs 9.4 +/- 1.4%, NS). Weight and insulin dose did not change significantly in any patient. Blood glucose control may deteriorate in young women with diabetes changed to insulin therapy with a pen-injector.

Adult↗
PubMed1991

Differential regulation of thyroid hormone receptor messenger ribonucleic acid levels by thyrotropin-releasing hormone.

In addition to its well known actions in stimulating TSH and PRL synthesis and secretion, TRH has been shown to decrease the concentration of thyroid hormone receptors (TRs) in GH4C1 cells as measured by nuclear thyroid hormone (T3) binding. In the present study we have investigated the effects of TRH on the levels of mRNA encoding the different forms of TR, TR beta-1, TR beta-2, and TR alpha-1 as well as that of the non-T3-binding variant, c-erbA alpha-2. GH3 cells were incubated with 100 nM TRH in the presence or absence of 1 nM T3 for 48 h, and mRNA levels were determined by Northern blot analysis. Results revealed that there is differential regulation of the individual TRs by TRH at the pretranslational level. The mRNA for the pituitary-specific form of TR, TR beta-2, was down-regulated by 60% by TRH in GH3 cells, while that of its alternative splice product, TR beta-1, was unchanged. A modest change was observed in TR alpha-1 mRNA levels, which were down-regulated by 20%; there was no change in c-erbA alpha-2 mRNA levels. Levels of nuclear T3 binding were assessed under the same conditions, and 100 nM TRH was found to decrease binding by 40% from 0.78 to 0.46 fmol/micrograms DNA. A similar change in nuclear T3 binding was seen after incubation with 1 nM T3. The effect of TRH on the GH mRNA response to T3 was investigated. In the absence of TRH there was a 4-fold induction of GH mRNA after incubation with 1 nM T3. In the presence of 100 nM TRH, no significant induction in GH mRNA by T3 was seen, indicating that T3 responsiveness as well as receptor concentration are diminished by TRH under these conditions.

Adenoma↗