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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 37 records · Page 2Linked to original sources

Neurotrophic activities of normal and motor neurone disease patient skeletal muscle extract on cultured rat spinal neurones.

Cultured foetal rat spinal neurones, grown in serum-free medium from day 3, respond to neuronotrophic factors present in adult human skeletal muscle extracts. Levels of total protein, neurofilament protein and choline acetyltransferase (ChAT) activity are all increased approx. 2 to 3-fold at 200 micrograms extract/ml medium. Culture survival is also extended from an average of 21 days to more than 30 days. Extracts prepared from skeletal muscle biopsies of motor neurone disease (MND) patients do not differ significantly from non-MND patient muscle extracts in their ability to boost the parameter levels or survival of the cultures. The results show no evidence that neuronotrophic factors are lacking in the skeletal muscle of MND patients.

Animals

Pion therapy at TRIUMF. Treatment results for astrocytoma grades 3 and 4: a pilot study.

At TRIUMF, (located on the University of B.C. Campus), 53 patients with supratentorial astrocytoma grades 3 and 4 were treated with pions between 1982 and 1985. A 3-dimensional spot-scanning treatment technique has proven to be practical. The accuracy of the beam alignment system used for treatment was reproducible daily within 2 mm. Low pion flux has hindered optimal beam shaping but this will soon be remedied as flux improves. The overall median survival observed (53 patients) is 262 days from date of first radiation treatment. Younger (less than 49 years) patients have significantly better survival than older (greater than 50 years) patients (p = 0.001). From a base line dose of 40 Gy photons whole brain and 17.5 Gy pion boost, doses were escalated to 33 Gy pions localised to the primary tumour and the median survival improved from 198 to 436 days. Survival curves for patients treated with localised pion techniques to doses above 30 Gy are significantly better than for those treated with schedules of pions mixed with photons (p = 0.04). It appears that optimal pion dose for brain tumours is 33 Gy minimum with a possible maximum of 36 Gy and doses delivered in 15 fractions in 3 weeks. Requirements for future trials are discussed.

Adult

Inferior turbinectomy: comparison of four techniques.

As yet, there is not totally satisfactory means for treating hypertrophied turbinates and the proper management of turbinate dysfunction remains in question. In the present series, four of the widely practiced surgical procedures for the reduction of the size of the inferior turbinates were evaluated and compared. In all cases turbinectomy was performed as an isolated procedure. Eighty patients with chronic non-allergic rhinitis and hypertrophied inferior turbinates were selected, randomly divided into four groups, and followed up post-operatively for one year. Study of the results indicated that the beneficial effect of the operation is mainly mechanical by reduction of the resistance to nasal airflow. The post-operative improvement in smell acuity correlated positively with the increased patency of the nasal airway. None of the procedures had a deleterious effect on olfactory acuity. In contrast, the operation failed to enhance the mucociliary clearance rate or significantly decrease nasal drainage. Partial inferior turbinectomy and laser turbinectomy improved nasal breathing in 77 per cent of patients, and enhanced olfactory acuity in 78 per cent of patients who had pre-operative hyposmia. The results of turbinoplasty and cryoturbinectomy were less favourable. The surgical technique, advantages, and drawbacks of each of these procedures are discussed.

Adult

Dementia, depression and physical disability in a London borough: a survey of elderly people in and out of residential care and implications for future developments.

We studied 1303 of the 1471 elderly people resident in Local Authority homes, NHS long-stay wards (medical and psychiatric), private and voluntary homes and Local Authority sheltered housing or in receipt of augmented domiciliary services in the London Borough of Waltham Forest. Depression and dementia were assessed using the Brief Assessment Schedule and physical functioning by a modified Barthel index. Residents with high levels of dependency were spread throughout the different forms of residential accommodation. There was little disability outside residential care. There was a high prevalence of depression in the study population. These findings are relevant to future plans for services for elderly people.

Aged

Antibodies to xanthine oxidase: elevated levels in patients with acute myocardial infarction.

Circulating antibodies to whole dried cows' milk, previously reported to be elevated in patients with myocardial infarction, have been shown to be directed mainly to the bovine milk fat globule membrane. Human antibodies against the bovine milk fat globule membrane themselves interact primarily with the enzyme, xanthine oxidase. Comparison of anti-(xanthine oxidase) antibody levels in 107 patients, who had suffered a myocardial infarction, with those in 86 control subjects showed significantly higher IgM levels in the patients with myocardial infarction. No corresponding differences were found for IgG or IgA anti-(xanthine oxidase) antibodies. Total levels of IgM class immunoglobulins did not differ between patients and controls. Serial assays following myocardial infarction showed no evidence that raised levels of IgM anti-(xanthine oxidase) antibodies result from the infarction itself.

Antibodies

Experimental infection of timed-pregnant rhesus monkeys with simian immunodeficiency virus (SIV) during early, middle, and late gestation.

Ten rhesus monkeys were inoculated with SIV/DeltaB670 during various stages of gestation to determine factors predictive of transplacental infection. Two abortions associated with rapid disease occurred shortly after infection; uninfected infants were caesarean delivered from eight other females. SIV-specific RNA accompanied by deciduitis was identified in the maternal portion of two placentas suggesting that opportunistic infections may promote entry of SIV into placental tissue. The lack of evidence for SIV infection of caesarean delivered infants suggests that fetal infection may often occur during parturition.

Abortion, Spontaneous

Substrate specificity of human fibroblast stromelysin. Hydrolysis of substance P and its analogues.

To probe the substrate specificity of the human metalloproteinase stromelysin (SLN), we determined values of kc/Km for the SLN-catalyzed hydrolysis of substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2; SP; kc/Km = 1790 +/- 140 M-1 s-1), 15 analogues of SP, and 17 other peptides. We found a remarkably narrow substrate specificity for SLN: while SP and its analogues could serve as substrates for SLN (hydrolysis occurred exclusively at the Gln6-Phe7 bond), peptides that were not direct analogues could not (kc/Km less than 3 M-1 s-1). From the study of the SLN-catalyzed hydrolysis of SP and its analogues, the following findings emerged: (1) Decreasing the length of SP results in decreases in kc/Km. (2) Conservative amino acid replacements near the scissle bond of SP decrease kc/Km. (3) The SP analogue in which Gly9 is replaced with sarcosine (N-methylglycine) is not hydrolyzed by SLN (kc/Km less than 3 M-1 s-1). (4) Several SP analogues that are not hydrolyzed by SLN are inhibitors of the enzyme. The complexes formed from interaction of SLN with these peptides have dissociation constants that are similar to the Km value for the complex of SLN and SP. Combined, these results suggest that SLN uses the energy that is available from favorable interactions with its substrate to stabilize catalytic transition states but not the Michaelis complex or other stable-state complexes.

Amino Acid Sequence

A semicontinuous, high-performance liquid chromatography-based assay for stromelysin.

A search for low molecular weight peptide substrates for the metalloendoproteinase, human fibroblast stromelysin, resulted in the discovery that substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) is a substrate for this enzyme and is cleaved exclusively at the Gln6-Phe7 bond. On the basis of this observation, a semicontinuous HPLC-based assay was developed that monitors the production of the hydrolysis product, fragment 7-11 (SP7-11). Steady-state velocities for the production of SP7-11 have been determined as a function of substrate concentration and obey simple, Michaelis-Menten kinetics. For a 1-ml reaction volume, Vmax = (2.4 nmol SP7-11/min)/micrograms protein and Km = 0.38 mM.

Chromatography, High Pressure Liquid

Bitewing radiographs of children taken with and without a film-holding device.

To help minimize radiation exposure, all dental radiographs must yield maximum diagnostic information. Film-holding devices have been recommended as a means of improving the diagnostic yield. Our study compared the diagnostic quality of bitewing radiographs of children taken with and without the aid of a film-holding device. 1014 bitewing radiographs (sizes 0, 1, 2) were taken of 338 children (aged 5-11 years) by senior dental students. Bitewing tabs were used for 554 radiographs and a film-holding device for the remainder. Diagnostic quality was calculated for each radiograph by dividing the number of non-overlapped contacts by the total number present. Both overall mean diagnostic yield and mean diagnostic yield for each size of film were found not to be significantly improved by use of the film-holding device. Position of overlapped contacts on each size of film was not equally distributed (P less than or equal to 0.01) among the contacts present. For size 0 and 1 films, overlap was most frequent between the maxillary first and second primary molars and for size 2 films between the maxillary first permanent molar and second primary molar/second bicuspid.

Adolescent

An ELISA for the detection of anti-acetylcholine receptor antibodies using biotinylated alpha-bungarotoxin.

An antibody-capture enzyme immunoassay has been developed for the detection of anti-acetylcholine receptor (AChR) antibodies in tissue culture supernatants using biotinylated alpha-bungarotoxin (B alpha BGT). Immunoglobulins in culture supernatants were bound indirectly to microtitre plates via an anti-globulin antibody already coupled to polyvinyl plates. Anti-AChR antibodies were then detected by incubation with AChR crude extract. Bound AChR was revealed by incubation with B alpha BGT followed by horseradish peroxidase-conjugated avidin. This assay is specific, more sensitive than the commonly used double antibody radioimmunoassay, avoids the use of radioactive material, is practical for large numbers of samples and is particularly suitable for detecting anti-AChR antibodies in tissue culture supernatants.

Animals

The "diff-if". Use of microcomputer analysis to triage blood specimens for microscopic examination.

Increasingly, all automated blood counts are not accompanied by a microscopic white blood cell differential. A popular strategy is to obtain a manual differential if any part of the automated blood count and differential is outside specified limits (the "diff-if" strategy). The authors compared two sets of criteria to triage blood counts for manual differentials: previously recommended numeric values, and the analysis of a microcomputer program. In a population of subjects with a high percentage of hematologic disorders, the microcomputer program and the numeric criteria were equally specific (excluding normal blood smears); the program was more sensitive for bands, immature granulocytes, monocytes, nucleated red blood cells, reticulocytosis, teardrops, red blood cell fragments, and hypersegmented neutrophils. The numeric criteria were more sensitive for eosinophilia (less than 1.0 X 10(9)/L) and mandated fewer manual differentials. In a population of predominantly normal subjects, the program was more sensitive for increased bands and equally sensitive for eosinophilia, the only abnormalities observed on the smear. In a population of subjects with predominantly abnormal blood counts, but excluding most primary hematologic disorders, there were few blood smears with abnormalities beyond eosinophilia or increased bands. In both of these groups, the computer program mandated more manual differentials than did the numeric criteria. The authors conclude that microcomputer analysis by the program tested was more sensitive than numeric criteria to identify specimens with abnormal blood smears. Specificity depended on the patient population. The choice of a triage strategy should be based on the individual laboratory's patient population.

Blood