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Biomedical subjects

C May

Publications and source records attributed to C May.

At least 91 records · Page 5Linked to original sources

Converting enzyme inhibition in rabbits: effects on sodium and water intake/excretion and blood pressure.

Earlier studies in rabbits revealed that in this species, in contrast to most other species studied, water intake was not influenced by injection or infusion of angiotensin II (ANG II). In order to establish whether ANG II has any role in the regulation of water intake of rabbits, a comprehensive study of the effect of converting enzyme inhibition was undertaken. Enalaprilat was given systemically in various doses to sodium- and water-replete, sodium-deplete, and water-deprived rabbits, and the intake and excretion of water and sodium was measured. In replete rabbits systemic injection of enalaprilat, 8 mg/kg and 8 micrograms/kg, but not 0.8 mg/kg, was followed by increased daily water intake. In sodium-deplete rabbits injection of enalaprilat, 80 mg/kg, was followed by water drinking within 1 h, and daily sodium intake was reduced. Systemic administration of ANG II increased, but did not restore to control level the sodium appetite of sodium-deplete rabbits attenuated by 80 mg/kg enalaprilat. Rabbits deprived of water for 24 h, however, drank the same amount of water after injection of vehicle or enalaprilat, 80 and 8 mg/kg. The efficacy of converting enzyme inhibition was also tested by measuring the blood pressure response to ANG I. Blood pressure responses revealed that in replete animals converting enzyme activity was depressed below control levels for 30 h after injection of 80 mg/kg enalaprilat. In sodium-deplete rabbits blood pressure fell following injection of 80 mg/kg enalaprilat and did not return to control level until 48 h after the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Canine distemper virus transcripts detected in the bone cells of dogs with metaphyseal osteopathy.

Using the technique of in situ hybridisation, we have recently extended our observations that canine distemper virus (CDV) is present in the bone cells of patients with Paget's disease, and have shown that CDV is also detectable in the bone cells of dogs that are naturally infected with the virus. Since hybridisation was localised to bone cells within the metaphyses of the affected dogs, we investigated the possibility that CDV might be involved in the canine metaphyseal bone disorder, metaphyseal osteopathy. Bone samples from three cases of metaphyseal osteopathy were examined for the presence of the CDV nucleocapsid (CDV-N) gene and the measles virus nucleocapsid (MV-N) gene, using 35S-labelled sense and antisense riboprobes. As with our previous findings in Paget's disease of bone, only the antisense probe was found to hybridize to the osteoblasts and osteoclasts within the affected metaphyses. No hybridisation was seen with the CDV-N sense and MV-N probes in any of the samples tested. Bone samples were also taken from one of the cases to check for the presence of the CDV-N gene using the polymerase chain reaction (PCR). Our findings with in situ hybridisation were confirmed by PCR and subsequent Southern blotting and probing with a 32P-labelled cDNA probe. The detection of CDV RNA within the bone cells of dogs with metaphyseal osteopathy suggests that this virus may be a cause of the disease and provides further, indirect evidence that CDV might be responsible for the bony abnormalities seen in Paget's disease of bone.

Animals↗

Disclosure of terminal prognoses in a general hospital: the nurse's view.

Some of the issues which nurses confront when they deal with the disclosure of terminal diagnoses and prognoses to patients are explored. In such circumstances, the nurse must respond to the competing demands of patients, relatives and medical staff. The paper examines the way in which a group of experienced staff nurses in a general hospital accounted for their activities during and after the disclosure of a lethal diagnosis. In particular, it explores the ways in which nurses are included or excluded from decision making about disclosure by medical staff.

Attitude of Health Personnel↗

Expression of TTK, a novel human protein kinase, is associated with cell proliferation.

We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation.

Amino Acid Sequence↗

Detection of canine distemper virus in bone cells in the metaphyses of distemper-infected dogs.

In the light of recent evidence implicating canine distemper virus (CDV) as a possible etiologic agent in Paget's disease of bone, we thought that it would be of interest to examine distemper-infected bone in the natural host. Samples from the long bones, spleen, and bladder of four distemper-infected and three uninfected dogs were examined for the presence of CDV nucleocapsid and phosphoprotein genes and the measles virus (MV) nucleocapsid gene using the technique of in situ hybridization with radioactively labeled riboprobes. Two of the four distemper-infected dogs showed strongly positive hybridization with both of the CDV probes. The signal was present in marrow cells, in osteoblasts, in osteocytes, and particularly in osteoclasts. No hybridization was seen over the cartilage cells of the growth plate, and there was a clear line of demarcation at the point of invasion of osteoclasts and vascularization. The spleen and bladder samples from infected dogs also showed positive hybridization. There was no hybridization with the MV probe in any of the distemper-infected tissue. Samples from the uninfected dogs showed no evidence of hybridization with either the CDV or MV probes. These results show that CDV can infect bone cells of the natural host and provide further support for the theory that CDV may play a role in human Paget's disease of bone.

Animals↗

Digital radiography in urologic imaging: radiation dose reduction on urethrocystography.

Digital luminescent radiography (DLR) is a new form of digital radiographic technology which can be used as an alternative to conventional radiologic systems; it replaces conventional screen-film systems by photostimulable phosphorus. Due to the linear dynamic range of photostimulable phosphorus, x-ray examinations can be performed with significantly lower radiation exposure. In this study radiation dose was reduced by about 90% using DLR for urethrocystography.

Humans↗

Lymphocyte populations in the synovial membranes of dogs with rheumatoid arthritis.

Lymphocyte populations in the synovial membranes of dogs with canine rheumatoid arthritis (CRA) were investigated by immunohistochemical staining techniques. T-lymphocytes were the predominant cell type distributed throughout the supporting layer of the synovial membranes. B-lymphocytes expressing IgG were seen far more commonly than those expressing either IgA or IgM. Synovial membrane biopsies from normal and osteoarthritic joints did not have the marked cellular infiltrates seen in joints with CRA. The synovial immunohistopathological features in dogs with CRA are similar to those seen in human rheumatoid arthritis.

Animals↗

T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction.

Interleukin 2 (IL-2)-induced tyrosine phosphorylation appears to play a major role in IL-2-induced cellular proliferation. Several intracellular substrates including the beta chain of the IL-2 receptor complex (IL-2R beta), raf, MAP2 kinase, the regulatory 83 kDa subunit of phosphatidylinositol-3 kinase and S6 kinases are substrates for the IL-2 receptor activated kinase(s). However, none of the identified members of the IL-2 receptor complex exhibits intrinsic tyrosine kinase activity. Therefore, the IL-2R complex must activate intracellular tyrosine kinases. We have demonstrated that specific tyrosine and serine/threonine kinases are coprecipitated with IL-2 receptor constructs that mediate IL-2-induced cell proliferation but not with those that do not. The IL-2-activated tyrosine kinase appears to be associated with a serine and proline rich intracellular domain which is highly conserved between IL-2R beta and the erythropoietin receptor. Although the responsible kinase has not been identified, lck, fyn, fgr, ltk, hck and lyn can be ruled out as obligatory mediators. Using methods to clone tyrosine kinases from T cells, we have identified potential candidate kinases, including several which had not been known to be expressed by T lymphocytes as well as several unique kinases which had not been previously identified in any cell type.

Amino Acid Sequence↗

Neither the LCK nor the FYN kinases are obligatory for IL-2-mediated signal transduction in HTLV-I-infected human T cells.

IL-2 is one of the principal growth factors regulating the proliferation of T lymphocytes. Although two independent IL-2-binding molecules have been molecularly cloned and shown to participate in the formation of a high affinity receptor complex, their primary structures do not suggest a specific mechanism for IL-2 growth signal transduction across the cell membrane. Neither IL-2 receptor subunit contains an intrinsic kinase domain; nevertheless, tyrosine phosphorylation of various intracellular substrates is one of the first biochemical changes observed following activation of the IL-2 receptor (IL-2R). Both serine/threonine and tyrosine kinases can be co-precipitated as part of the IL-2R complex suggesting that the IL-2 signalling may involve the activation of non-covalently associated intracellular kinases. However, controversy exists as to which kinases are involved in IL-2 signal transduction; in particular, which kinase(s) mediates the first or proximal event(s) in the signalling process. Activation of the IL-2R leads to serine and threonine phosphorylation of the SRC tyrosine kinase family member, LCK, and an increase in LCK tyrosine kinase activity. Furthermore, LCK can be co-immunoprecipitated with the beta chain of the IL-2R indicating its association with the receptor complex. IL-2 has also been reported to increase FYN kinase activity and to alter its association with the 85 kDa subunit of phosphatidylinositol-3 kinase thus suggesting a role for FYN in IL-2 signal transduction. However, in this report, we now demonstrate that neither LCK nor FYN are obligatory for IL-2-induced growth of HTLV-I-infected human T cells. Lack of expression of LCK or FYN in the HTLV-I-infected T cell lines was demonstrated by a combination of Northern blotting, polymerase chain reaction, Western blotting, and in vitro kinase activity. Despite the absence of LCK or FYN, IL-2 induced similar patterns of rapid tyrosine phosphorylation. Similar results were observed in cell lines lacking expression of the LYN, FGR, HCK, and LTK tyrosine kinases. Thus, none of these tyrosine kinases alone appears to be required for growth signalling through the IL-2R in the HTLV-I-infected T cell lines analyzed. The findings raise the possibility that an, as yet, unidentified tyrosine kinase is involved. Alternatively, this biological signalling system may exhibit remarkable redundancy whereby several different tyrosine kinases may be capable of associating with the IL-2R complex and mediating intracellular signalling.

Cell Division↗

Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia.

In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation.

Bradycardia↗

A burning issue? Adolescent alcohol use in Britain 1970-1991.

A review is presented of British research related to alcohol use and misuse by adolescents in the period 1970 to 1991. The stability of alcohol use among this age group is emphasised by a succession of studies which indicate the normality of alcohol consumption among its members, most of whom drink in moderation. It is noted that a succession of 'moral panics' amplified in the popular media have led to public concern about an 'epidemic' of alcohol misuse by young people, but that research evidence does not sustain this popular supposition. Nevertheless, the available evidence does support the conclusion that alcohol misuse is a major problem for a small proportion of young people.

Adolescent↗

Affective neutrality and involvement in nurse-patient relationships: perceptions of appropriate behaviour among nurses in acute medical and surgical wards.

This paper explores ideas about the appropriate basis for nurse-patient relationships which underwrite the nursing practice of experienced staff nurses on the acute surgical and medical wards of a Scottish general hospital. Three central features of involvement with patients are identified, knowledge, reciprocity and investment, and these are related to three general models of the nurse-patient relationship, characterized as primary, demonstrative and associational. The implications of the nursing practice on which these models are based are discussed in the context of issues of quality of care and orientation to work.

Affect↗

Cerebrospinal fluid acetylcholinesterase in progressive supranuclear palsy: reduced activity relative to normal subjects and lack of inhibition by oral physostigmine.

Acetylcholinesterase (AChE) activity was measured in lumbar cerebrospinal fluid (CSF) of 11 patients with progressive supranuclear palsy (PSP) and 18 age-matched healthy control subjects. Mean CSF AChE activity in PSP subjects was significantly reduced by 31% relative to control subjects (p less than 0.002). In the light of evidence of a central cholinergic deficit, physostigmine was administered orally (0.5-2.0 mg every two hours, six times a day for 10 days) to eight of the 11 PSP patients. CSF was sampled when the patients were on placebo and when receiving physostigmine and CSF AChE and butyrylcholinesterase (BChE) activities were measured. There was no significant change in either CSF AChE or BChE activities following physostigmine treatment. These data suggest that the doses of physostigmine used were insufficient to produce marked inhibition of AChE within the central nervous system.

Acetylcholinesterase↗

Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications.

To explore whether possible differences in central nervous system neuromodulators contribute to the differential presentation of affective symptomatology in Cushing's disease and major depression, we examined the levels of immunoreactive CRH and ACTH in the cerebrospinal fluid (CSF) of 11 patients with Cushing's disease, a patient with ectopic ACTH secretion, 34 patients with major depression, and 60 healthy subjects. We elected to measure these peptides not only because both are classically involved in pituitary-adrenal regulation, but also because their primarily arousal-producing and anorexigenic behavioral effects in experimental animals suggest that they may play a role in the symptom complex of depressive syndromes. We also explored whether the CSF levels of these peptides were more helpful in determining the often difficult differential diagnosis between major depression and Cushing's disease than the plasma ACTH response to ovine CRH, a currently used but somewhat insensitive laboratory means of distinguishing these disorders. CSF levels of immunoreactive CRH and ACTH were significantly lower in Cushing's disease patients [21.9 +/- 2.7 and 15.4 +/- 1.8 pg/mL, (mean +/- SEM), respectively] compared to patients with major depression [38.4 +/- 2.3 pg/mL (P less than 0.01) and 24.5 +/- 1.6 pg/mL (P less than 0.01), respectively] and controls [38.4 +/- 1.6 pg/mL (P less than 0.001) and 26.3 +/- 1.1 pg/mL (P less than 0.001), respectively]. The coexistence of high plasma ACTH and low CSF ACTH in Cushing's disease yielded a CSF/plasma ACTH ratio consistently less than that in depressed patients, with only 2 of 31 subjects comprising both groups showing values that overlapped. In contrast, 9 of the combined patients showed ACTH responses to ovine CRH that overlapped. These data suggest that differences in centrally directed CRH secretion may account for the differential presentation of the dysphoric syndromes seen in major depression and Cushing's disease. Hence, the classic form of major depression (melancholia), is often associated with evidence of pathological hyperarousal, such as intense anxiety, sleeplessness, and anorexia, while that of Cushing's disease is associated with evidence of pathological hyperarousal, including hyperphagia, fatigue, and inertia. Moreover, measurement of the CSF/plasma ACTH ratio may serve as a clinically useful adjunct to the ovine CRH stimulation test and other laboratory measures in determining the differential diagnosis between major depression and Cushing's disease.

Adolescent↗