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Biomedical subjects

R MacKenzie

Publications and source records attributed to R MacKenzie.

At least 37 records · Page 2Linked to original sources
PubMed1997

Substitution of D-Trp32 in NPY destabilizes the binding transition state to the Y1 receptor site in SK-N-MC cell membranes.

The retention rate of the spin label 3-isothiocyanto methyl-2,2,5,5-tetramethyl-1-pyrrolidinyl oxyl spin label (proxyl) attached to the porcine N-acetyl-NPY peptide and the porcine N-acetyl-D-Trp32-NPY peptide at Lys4 was investigated using SK-N-MC neuroblastoma cell membranes containing the Y1 receptor. The release rate of the spin labeled peptides was monitored by electron spin resonance and the KD was determined by a direct radiolabeled NPY displacement binding assay. The analyses show that for the porcine [Ac-Tyr1N epsilon 4-proxyl]-NPY, the KD was 8 x 10(-10) M and koff was 2.7 x 10(-4) sec-1 yielding a value for kon of 3.3 x 10(5) sec-1 M-1. The [Ac-Tyr1, N epsilon 4-proxyl,-D-Trp32]-NPY antagonist ligand had a value of KD equal to 1.35 x 10(-7) M and koff was 1.7 x 10(-4) sec-1 leading to a value for kon of 1.2 x 10(3) sec-1 M-1. The difference in the kon rates of two orders of magnitude is interpreted as demonstrating the N-acetyl-N epsilon 4 proxyl-D-Trp32-NPY ligand binding transition state to be of higher energy then for the unmodified NPY amino acid sequence.

Amino Acid Sequence↗
PubMed1997

Perspectives on changing times: implications for insurance medicine.

Profound changes are occurring in medicine. These changes are in both medicine itself and also in the economic and social context. The driving forces for change include health care reform, sophisticated consumers, new technology, information explosion and ethics of controlling human biology.

Ethics, Medical↗
PubMed1997

Is selective neck dissection sufficient treatment for the N0/Np+ neck?

OBJECTIVE: The purpose of this study was to evaluate the therapeutic role of selective neck dissection performed electively in the N0 patient. METHOD: Fifty-four patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx, without clinical evidence of lymph node metastases, underwent 72 selective neck dissections over a 6-year period. The preoperative tumour and patient data were recorded in all patients. Mean follow-up was 59 months. Outcome data pertaining to pathologic nodal status, tumour recurrence, and survival were recorded on all patients. RESULTS: Eighty-one percent of patients were histologically and clinically node negative. Seven percent of N0/Np0 patients failed in the neck compared to 50% of patients with occult nodal metastases (N0/Np+). Salvage treatment following nodal recurrence was successful in only one patient. CONCLUSION: Selective neck dissection does not compromise survival and may minimize surgical morbidity in the N0/Np+ population.

Adult↗
PubMed1996

Structure-function relationships of human cholesteryl ester transfer protein: analysis using monoclonal antibodies.

Cholesteryl ester transfer protein (CETP), a 476 amino acid glycoprotein, mediates cholesteryl ester (CE), triglyceride, and phospholipid transfer among plasma lipoproteins. A monoclonal antibody (mAb), TP2, specific for an epitope within the last 26 amino acids of CETP has been shown to block all CETP-mediated lipid transfer, apparently by limiting access to lipid-binding sites in the carboxy terminal of CETP. A new panel of 16 anti-human CETP mAbs has now been used to further probe the structure-function relationships of CETP. Of the new mAbs, 9 partially inhibit CETP-mediated CE transfer (24-43%) from HDL to LDL. The corresponding epitopes were mapped within the CETP primary structure by the reactivity of the mAbs with CETP variants having deletions or amino acid substitutions. Of the 9 new, neutralizing mAbs, 6 are specific for epitopes situated between residues 410-450 and two others for epitopes between residues 184-260 and 332-366, respectively. The epitope of one neutralizing mAbs could not be mapped. Therefore, binding of mAbs to epitopes situated in four non-overlapping regions within CETP primary structure that are separated by as many as 280 residues can neutralize CETP-mediated CE transfer. Epitopes of mAbs that do not influence CE transfer activity map to the regions 184-260, 261-331, and 367-409, respectively. When pairs of mAbs were tested for their abilities to mutually compete for binding to immobilized CETP, competition was observed for mAbs specific for epitopes that are distant in CETP primary structure. The cross-competition patterns demonstrate that the carboxy terminal 60% of CETP adopts a compact structure. Together with previous mutagenesis studies, the data suggests that a carboxy terminal neutral lipid binding domain may be in close proximity to a lipoprotein binding region within native CETP.

Animals↗
PubMed1995

Patients' perceptions of magnetic resonance imaging.

There are several anxiety-related reactions associated with magnetic resonance imaging (MRI). Patients who experience such reactions may disrupt the examination or move so much that images are degraded. These experiences may also influence patients' perceptions of the quality of their care. The objective of this study was to further assess the subjective experiences of patients undergoing MRI in an attempt to identify those patients likely to have problems and factors affecting their experiences. Five hundred consecutive patients undergoing MRI were surveyed using questionnaires before and immediately after imaging. Anxiety was measured using the state anxiety component of the state-trait anxiety inventory. All patients exhibited some degree of pre-imaging anxiety. This was particularly associated with a previous 'unpleasant' imaging experience. Patients who experienced problems during MRI had pre-imaging anxiety levels equivalent to patients about to undergo surgery, were more likely to react badly when first seeing the scanner and were more likely to leave the MRI unit with even greater feelings of anxiety than when they arrived. In contrast to previous studies, anxiety was not associated with either the patient's understanding of the procedure or the duration of the examination. Several features have been identified which could improve the patient's experience (e.g. better information sheet). Awareness of MRI-related anxiety should also be considered when assessing the impact of MRI on outcome for the patient.

Adolescent↗
PubMed1995

Molecular characterization of two monoclonal antibodies specific for the LDL receptor-binding site of human apolipoprotein E.

Apolipoprotein E (apoE), a 299 amino acid protein, is a ligand for the low density lipoprotein receptor (LDLr). It has been established that basic amino acids situated between apoE residues 136 and 150 participate in the interaction of apoE with the LDLr. Evidence suggests that apoE is heterogeneous on lipoproteins in its conformation and in its ability to react with cell surface receptors. Our goal was to produce mAbs that could serve as conformational probes of the LDLr binding site of apoE. We used a series of apoE variants that have amino acid substitutions at residues 136, 140, 143, 144, 145, 150, 152, and 158 to identify the epitopes of two anti-human apoE monoclonal antibodies (mAbs), 1D7 and 2E8, that inhibit apoE-mediated binding to the LDLr. We show that most of the variants that have reduced reactivity with the LDL receptor also have reduced reactivity with the mAbs. The epitopes for both mAbs appear to include residues 143 through 150 and thus coincide with the LDLr-binding site of apoE. It is notable that mAb 2E8, but not 1D7, resembles the LDLr in showing a reduced reactivity with apoE (Arg158 --> Cys). While most of the receptor-defective variants involve replacement of apoE residues directly implicated in binding, substitution of Arg158 by Cys is thought to indirectly affect binding of apoE to the LDLr by altering the conformation of the receptor-binding site. To determine whether the similarity in specificities of the mAbs and the LDLr reflect structural similarities, we cloned and characterized the cDNAs encoding the light and heavy chains of both mAbs. Primary sequence analysis revealed that, although these two antibodies react with overlapping epitopes, their respective complementarity determining regions (CDRs) share little homology, especially those of their heavy chains. The two mAbs, therefore, likely recognize different epitopes or topologies within a limited surface of the apoE molecule. Four negatively charged amino acids were present in the second CDR of the 2E8 heavy chain that could be approximately aligned with acidic amino acids within the consensus sequence of the LDLr ligand-binding domain. This could indicate that mAb 2E8 and the LDLr use a common mode of interaction with apoE.

Amino Acid Sequence↗
PubMed1994

Long-term prognosis after peri-operative cardiac complications.

UNLABELLED: The objective was to document the 5 year prognosis of patients who had cardiac complications after non-cardiac surgery. DESIGN: 5-year follow-up of 218 patients originally enrolled in a prospective study to identify risks factors for peri-operative complications. SETTING: an academic medical center. Participants were hypertensives and diabetics who underwent elective surgery between 1982 and 1985. In the original study, patients were evaluated pre-operatively, monitored intra-operatively by an independent observer, and followed daily for 7 days post-operatively according to a standard surveillance protocol. Outcomes were judged by assessors blinded to the pre-operative status and intra-operative course. Patients were interviewed at 3 and 5 years post-operatively. Patients with post-operative cardiac complications had significantly higher rates of overall mortality, mortality attributable to cardiac causes (MI, CHF, arrest), and mortality attributable to other cardiovascular causes (stroke, renal failure) than patients without cardiac complications. For example, at 5 years 11% of those patients without post-operative cardiac complications had cardiac deaths, in contrast to 45% of those patients with post-operative cardiac complications. Proportional hazards analysis demonstrated that post-operative cardiac complications remained a significant predictor of cardiac (p < 0.001) and cardiovascular (p < 0.0001) mortality controlling for pre-operative cardiac disease, other non-cardiovascular comorbid diseases, age, sex, diabetes, and pre-operative renal insufficiency or stroke. Similarly, patients with post-operative non-fatal cardiac complications had higher rates of cardiac or cardiovascular events during the 5 year follow-up period. We conclude that post-operative cardiac complications have a significant adverse long-term prognostic impact comparable to the prognostic impact of myocardial infarction, ischemia or congestive failure in the non-operative setting. Understanding these events could be an important factor in identifying patients at high risk for subsequent peri-operative complications.

Aged↗
PubMed1994

Lack of global vagal propensity in patients with oculocardiac reflex.

BACKGROUND: Profound bradycardia during ophthalmic surgery is a rare but potentially serious event. Little is known about the predictability of the oculocardiac reflex. METHODS: Four vagotonic maneuvers were performed on six patients who had profound oculocardiac reflex (3- to 10-second asystole) during eye surgery, the results of which were compared with 30 previously studied control subjects. Electrocardiographs were monitored during the following vagotonic maneuvers: diving response (apneic facial immersion), Valsalva maneuver, ocular compression, and carotid sinus massage. RESULTS: The degree of heart rate slowing as a result of diving response, Valsalva maneuver, and, notably, ocular compression did not differ when these patients were compared with the 30 previously studied control subjects. Carotid sinus massage produced significantly (P = 0.01) more bradycardia in the six patients (mean +/- standard deviation, -24% +/- 6%) than in the 30 control subjects (-12% +/- 7%). The heart rate response to pressure on the eyes did not correlate with prior intraoperative oculocardiac reflex. CONCLUSION: The discrepancy in heart rate sensitivity between surgical extraocular muscle tension and ocular compression may be due to different sensory receptors and brain stem processing for the trigeminally mediated oculocardiac reflex. Carotid sinus massage may help predict low heart rates during eye surgery.

Adult↗
PubMed1994

Clinical evaluation of liquid crystal skin thermometers.

We have examined two types of liquid crystal thermometers (LCT) designed for clinical use: one designed to measure skin surface temperature (LCTS) and the other had its calibration shifted by 1.9 degrees C to read a "core" temperature (LCTC). In laboratory tests with LCT on a glass beaker, there were highly significant correlations between temperatures measured by thermocouples, LCTS (r = 0.99) and LCTC (r = 0.99). In five patients undergoing cooling and warming during cardiopulmonary bypass with an LCT on their forehead, next to a thermocouple, the smallest correlation coefficient was 0.92. In 7.3% of observations in patients, the LCT scale was blurred, but readable. The graph relating LCT temperature and forehead thermocouple temperature showed hysteresis between the cooling and warming phases. An additional laboratory experiment suggested that LCT might be affected by draughts; they should therefore be protected from draught in use.

Cardiopulmonary Bypass↗
PubMed1993

A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma.

Two hundred and twelve patients with previously untreated advanced squamous carcinoma of the larynx or hypopharynx were randomized to receive initial treatment with radiotherapy, 50 Gy in 20 fractions in 28 days or split course radiotherapy and concurrent chemotherapy, 25 Gy in 10 fractions in 14 days followed by a 4 week rest and a further 25 Gy in 10 fractions in 14 days starting on day 43; Mitomycin C was given on day 1 and day 43 and 5FU continuous infusions on days 1--4 and days 43--46. Surgery was reserved for persistent or recurrent disease. Two hundred and nine of the 212 patients randomized were included in the analyses. Outcome analyses were performed at a median follow-up interval of 4.4 years. No patients were lost to follow-up. No significant difference was found between the two arms for the end points of local relapse-free rate (p = 0.91), regional relapse-free rate (p = 0.17, adjusted) or overall survival (p = 0.86). Eight-eight patients had attempted surgical resection following radiotherapy failure. The contribution of salvage surgery to overall survival was similar for both arms of the study as was the surgical complication rate. Serious late radiation toxicity was minimal (3% in the RT group, 0% in the radiation therapy plus chemotherapy group). The result of the trial shows no advantage in terms of local control or survival for the experimental treatment arm of split course radiotherapy and concurrent chemotherapy with Mitomycin C and 5 Fluorouracil compared to radiotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Attitudes and concerns amongst laboratory staff regarding handling of HIV positive biological specimens.

AIMS: to ascertain attitudes and concerns of laboratory staff towards handling of HIV positive biological samples. METHOD: an anonymous questionnaire regarding various aspects of biological sample handling was distributed to laboratory staff from the Wellington Area Health Board laboratories. RESULTS: of a total of 133 laboratory staff (response rate: 56.4%), five were seriously considering leaving, and another ten would have chosen another career if given prior information in regard to handling HIV positive biological samples. Of the responders, 22.8% and 38.3% considered that their employer does not provide adequate safety measures and education respectively in regard to HIV. CONCLUSIONS: handling of HIV positive biological samples does not greatly contribute to attrition amongst laboratory staff. Given the concern of laboratory staff for safety and education in regard to HIV, a continuous in-service educational programme would be desirable.

Attitude of Health Personnel↗
PubMed1992

Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels of New Zealand pesticide applicators and their implication for cancer hypotheses.

BACKGROUND: The phenoxyherbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) has been widely used by professional pesticide applicators in New Zealand since before 1950. Epidemiologic studies of the risk of cancer and birth defects have been conducted in this group of workers, but little is known about the extent of their exposure to the 2,4,5-T contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent carcinogen in animals. PURPOSE: The objective of this study was to determine whether the blood serum levels of TCDD in a group of professional 2,4,5-T applicators in New Zealand were greater than those of a matched control group not involved in 2,4,5-T spraying. METHODS: Of 548 men employed as professional pesticide applicators in New Zealand from 1979 through 1982, nine were selected who had sprayed pesticides, although not necessarily 2,4,5-T, for at least 180 months. These applicators had sprayed 2,4,5-T for a range of 83-372 months. We measured the blood serum levels of polychlorinated dibenzo-p-dioxins and dibenzofurans, which were substituted with chlorine at the 2,3,7,8 position, in the nine pesticide applicators and in a matched group of nine control subjects. RESULTS: The average serum level of TCDD for applicators was almost 10 times that for the matched control subjects, while the average levels of all other congeners and isomers measured in the two groups did not differ substantially. TCDD levels in eight of the nine applicators were higher than those in the control subjects (mean difference, 47.7 parts per trilion). The variation in TCDD levels among the applicators was related to their duration of work exposure to 2,4,5-T. CONCLUSIONS: On the basis of our findings in these subjects in New Zealand, we conclude that increased risks of cancer from brief exposure to phenoxyherbicides reported in other countries are probably not attributable to the TCDD that contaminates 2,4,5-T. We cannot determine from these results, however, whether TCDD exposure from prolonged use of 2,4,5-T poses significant health risks.

Humans↗
PubMed1992

A68930: a potent agonist specific for the dopamine D1 receptor.

A68930, [1R, 3S] 1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCl, is a potent, partial agonist in the dopamine-sensitive adenylate cyclase model of the D1 dopamine receptor in fish retina. In the rat caudate-putamen model of the D1 dopamine receptor, A68930 is a potent (EC50 2.1 nM) full agonist. In contrast, A68930 is a much weaker (EC50 = 3,920 nM) full agonist in a biochemical model of the D2 dopamine receptor. A68930 also displays weak 2 agonist activity but the molecule is virtually inactive at the 1 and beta-adrenoceptors. When tested in rats bearing a unilateral 6-OHDA lesion of the nigro-neostriatal neurons, A68930 elicits prolonged (> 20 hr) contralateral turning.

Adenylyl Cyclases↗