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Biomedical subjects

M G Brown

Publications and source records attributed to M G Brown.

At least 55 records · Page 3Linked to original sources
PubMed1993

Biochemical purification of distinct proteasome subsets.

Proteasomes are intricate cellular proteases that are able to degrade many protein and peptide substrates in vitro. These particles are structurally complex; they are assembled from at least 14 small molecular mass polypeptide subunits to form mature 20S proteasomes. Recently, we demonstrated that proteasome subsets may be discriminated by serological criteria, and have found that subtle differences in the subunit composition of proteasomes can alter their cleavage specificity. Proteasome structural complexity is further enhanced when some proteasomes associate with additional proteins to form a 26S ATP- and ubiquitin-dependent protease. Herein we confirm the existence of distinct cellular forms of proteasomes, and show that they differ in their hydrophobic characteristics. We have reproducibly purified, using solely biochemical techniques, distinct proteasome subsets similar to the serologically defined LMP2+ and LMP2- proteasomes. These proteasome subsets differ in their expression of at least three polypeptides, and both lack several additional polypeptides as compared to the serologically defined LMP2+ and LMP2- proteasomes. Finally, we demonstrate that these structurally unique proteasomes differ in their capacity to cleave a defined panel of fluorogenic peptide substrates. It appears that mammalian cells might recruit and modify proteasomes to perform distinct cellular tasks.

Amino Acid Sequence↗
PubMed1993

Rationing health care in Canada.

Canada has been able to develop a fairly successful system of healthcare rationing by balancing the conflicting concerns of equal access and cost efficiency, federal funding and provincial control, and public sector management and private sector provision. Financial constraints limit the kinds of services included within the notion of equal access, however, forcing healthcare providers to make difficult choices about who will receive a particular healthcare service.

Attitude to Health↗
PubMed1993

Results of 1236 endoscopic carpal tunnel release procedures using the Brown technique.

In a series of 1236 patients who underwent endoscopic carpal tunnel releases using the two-portal Brown technique, the results were favorable in 98%, the failure rate was 2%, the instance of iatrogenic injury was 0.08% (one tendon injury), and the overall complication rate was 0.97%. The patients had resolution of carpal tunnel syndrome symptoms in an average of 14 days and returned to work in an average of 15 days. Recurrence rate to date has been 2%, with the longest follow-up of 30 months. These results indicate that this is a safe and efficacious method of treatment for patients with carpal tunnel syndrome who require surgery.

Carpal Tunnel Syndrome↗
PubMed1993

Use of ophthalmologic services by diabetic patients in Nova Scotia.

To evaluate the possible public health consequences of diabetic retinopathy in Nova Scotia, we investigated the number and frequency of ophthalmologic examinations in patients with diabetes mellitus. A total of 36,683 people (4.2%) were identified from the administrative database of the provincial health department as having a diagnostic code of diabetes during the period March 1987 to February 1990. All billings by ophthalmologists for these patients during the same period were then identified. Of the 36,129 patients aged 10 years or more, 17,518 (48.5%) had seen an ophthalmologist at least once during the study period, and 5218 (14.4%) had seen an ophthalmologist approximately annually. Increased age and being female were associated in univariate logistic regression analysis with higher use of ophthalmologic services. The medical insurance system is free of direct costs to patients, and there are enough ophthalmologists to meet patient needs (4.35 per 100,000 population). The findings indicate that most diabetic patients in Nova Scotia are not seen at least once a year, as recommended by the Expert Committee of the Canadian Diabetes Advisory Board, despite ready availability of ophthalmologic care.

Adolescent↗
PubMed1992

Endoscopic carpal tunnel release.

We have performed 149 consecutive one-portal and 152 consecutive two-portal endoscopic carpal tunnel release operations. Average time to cessation of preoperative symptoms was 15 days in both the one-portal and two-portal groups. The average time of return to work was 16 days in the one-portal group and 17 days in the two-portal group. The complication rate in the one-portal group was 6%, and in the two-portal group it was 5%. In our opinion, the one-portal release technique is much more difficult and inherently more dangerous than the two-portal technique, and we recommend the latter for endoscopic carpal tunnel release.

Activities of Daily Living↗
PubMed1991

Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes.

Major histocompatibility complex (MHC) class I molecules associate with peptides derived from endogenously synthesized antigens. Cytotoxic T-lymphocytes can thus scan class I molecules and bound peptide on the surface of cells for foreign antigenic determinants. Recent evidence demonstrates that the products of trans-acting, non-class I genes in the class II region of the MHC are required in the class I antigen-processing pathway. There are genes (called HAM1 and HAM2 in the mouse) in this region that encode proteins postulated to be involved in the transport of peptide fragments into the endoplasmic reticulum for association with newly synthesized class I molecules. But, the mechanism by which such peptide fragments are produced remains a mystery. At least two genes encoding subunits of the low-molecular mass polypeptide (LMP) complex are tightly linked to the HAM1 and HAM2 genes. We show that the LMP complex is closely related to the proteasome (multicatalytic proteinase complex), an intracellular protein complex that has multiple proteolytic activities. We speculate that the LMP complex may have a role in MHC class I antigen processing, and therefore that the MHC contains a cluster of genes required for distinct functions in the antigen processing pathway.

Animals↗
PubMed1991

A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex.

The region of the murine major histocompatibility complex (MHC) between the Pb (A beta 3) and Ob (A beta 2) genes controls the expression of an intracellular complex named the LMP (low molecular weight polypeptide) complex. DNA probes for at least seven different genes mapping to this region were isolated. These hybridize to a minimum of eight different transcripts ranging from approximately 1.3 to 3.7 kilobases (kb). The deduced amino acid sequences of the corresponding cDNAs indicate that three of these genes are new members of the MHC class II gene family. These genes are transcribed in a tissue-specific pattern similar to that of the traditional class II genes. Two of the remaining four genes, HAM1 and HAM2, are homologous to one another and to a family of eukaryotic and prokaryotic transport proteins and may be involved in antigen processing. The tissue distribution of HAM1 transcripts is consistent with its proposed role in class I-restricted antigen processing, whereas HAM2 transcription appears more restricted and may be involved in antigen processing for class II-restricted T cells. The HAM2 gene may produce two differentially spliced transcripts. The identity of the remaining two genes is not known. Analyses of transcript sizes, tissue distribution, sequence, and genetic mapping data suggest that none of these genes code for LMP antigens.

Animals↗
PubMed1991

Glutamine-enhanced enteral diet improves nitrogen balance without increasing portal ammonia.

Following surgical stress the jejunum actively metabolizes endogenous glutamine, a non-essential amino acid, to produce alanine and ammonia, which augments substrate flow to the liver at a time when oral intake of nutrients is decreased. Oral glutamine supplementation theoretically may modify the response to injury. This study was designed to demonstrate the role of the jejunum in postinjury glutamine metabolism and to evaluate the influence of enteral glutamine supplements on nitrogen and ammonia metabolism after laparotomy and bowel resection in dogs. Oral glutamine in the presence of an intact small bowel significantly improved nitrogen balance (461 mg kg body-weight-1 day-1) compared with a control diet (-370 mg kg-1 day-1) (P less than 0.05, analysis of variance). Removal of the proximal small bowel prevented this beneficial effect of glutamine (-507 mg kg-1 day-1). Glutamine-supplemented and control diets were associated with similar portal ammonia concentrations throughout the study.

Ammonia↗
PubMed1990

Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences.

It has recently been shown that apparently similar deletions of chromosome 15q occur commonly in the Prader-Willi and Angelman syndromes. The distinctness of the syndromes suggests that the deletions are not identical. To address this possibility, the specific bands involved and the sizes of the deletions were compared in seven patients with Prader-Willi syndrome and 10 patients with Angelman syndrome using high-resolution G-, Q-, and fluorescent R-banding techniques. The parental origin of the nine cases of Angelman syndrome for which parents were available for study was determined. The same proximal band was deleted (q11.2) in both syndromes. In general, the deletion in patients with Angelman syndrome was larger, though variable, and included bands q12 and part of q13. All of the studied deletions in patients with Angelman syndrome were of maternal origin. This contrasts with the predominant paternal origin of the deletion in patients with Prader-Willi syndrome. Two possible reasons for these observations are postulated: 1) the deleted regions are different at the cytologic and/or molecular level because of different exchange points in meiosis in males and females or to different mechanisms of breakage in males and females, resulting in differing breakpoints; 2) the deleted regions are essentially the same, but differential expression of the genes in the homologous chromosome 15 has occurred (imprinting).

Adolescent↗
PubMed1988

Effect of removal of lacrimal and third eyelid glands on Schirmer tear test results in cats.

Schirmer tear tests I and II values for 10 healthy cats were 16.2 +/- 3.8 mm/min and 13.2 +/- 3.4 mm/min, respectively. Surgical removal of the lacrimal gland or the third eyelid gland from the left eye resulted in decreased Schirmer tear test-I values. Clinical signs of keratoconjunctivitis sicca were not seen until the lacrimal and third eyelid glands were removed, at which time the Schirmer tear test-I value was close to 0 mm/min. Conjunctival glands (accessory lacrimal glands of Krause and Wolfring) appeared to contribute little to tear production in these cats.

Animals↗
PubMed1988

Parental origin of the extra chromosome in the cat eye syndrome: evidence from heteromorphism and in situ hybridization analysis.

Two individuals, a boy and girl, with a clinical diagnosis of cat eye syndrome had an extra bisatellited chromosome. In the girl, the diagnosis was made on the basis of coloboma of the right iris, right preauricular pit, and imperforate anus; in the boy, bilateral colobomata of the iris, down-slanting palpebral fissures, right preauricular skin tag, and right preauricular pit. Multiple staining techniques were used to characterize the extra chromosomes. With G-banding the extra chromosome usually appeared monocentric with two major G-positive bands, but with satellites on both ends; with C-banding, two C-band positive regions were evident, indicating that the chromosomes were likely dicentric. Silver staining demonstrated the presence of NORs near each end; Q-banding showed satellites on each end, differing in brightness and size. The chromosomes of the parents were normal; comparisons of Q-band heteromorphisms of the acrocentric chromosomes of the parents with those of the extra chromosome showed in each case one short arm/satellite region of the extra chromosome identical in appearance to one chromosome 22 of the mother and the other end of the extra bisatellited chromosome identical to the short arm/satellite of the mother's second chromosome 22. This extra chromosome, then, is the result of a maternal meiotic error in each case. In situ hybridization studies using the chromosome 22-derived probe p22/34, which identifies locus D22S9, showed 16% of the cells from the female patient to have silver grains on the proximal long arm of the normal chromosome 22 and 14% on the extra chromosome, while 10% of cells from the male had grains on the normal chromosomes 22 and an equal number on the extra chromosome, confirming the chromosome 22 origin of the extra chromosome in these patients.

Abnormalities, Multiple↗
PubMed1987

Y-derived sequences detected in a 45,X male by in situ hybridization.

A two-month-old boy with normal genitalia and descended testes was referred for a suspected hematological disorder. Cytogenetic analysis showed a 45,X chromosome constitution. In situ hybridization with the Y-derived probe 50f (provided by Professor Marc Fellous) was performed utilizing metaphase chromosomes to determine whether Y material could be detected. A significant amount of label (17 of 150 cells) was found on chromosome 5p suggesting a 5;Y translocation. This translocation was verified by high-resolution G-banded and G-11-stained chromosomes.

Child, Preschool↗
PubMed1987

Is Angelman syndrome an alternate result of del(15)(q11q13)?

Two unrelated females, age 15 and 5 years respectively, were studied cytogenetically because of severe mental retardation, seizures and ataxia-like incoordination. A similar deletion of the proximal long arm of chromosome 15 was found in both patients. Re-evaluation showed no voracious appetite or obesity; normal size of hands and feet, minimal to no hypotonia by history or examination and facial features not typical of the Prader-Willi syndrome. However, the facial appearance of the girls was similar to each other with mild hypertelorism. The similarity of these girls and dissimilarity to Prader-Willi syndrome suggest a different syndrome, perhaps the result of deletion of a different segment of 15q. The findings of ataxic-like movements, frequent, unprovoked and prolonged bouts of laughter and facial appearance are more compatible with the diagnosis of Angelman syndrome.

Adolescent↗
PubMed1987

UV radiation measurement in a study of elderly subjects.

Elderly subjects were exposed to controlled amounts of sunshine over a 3-month period. Ultraviolet radiation (UVR) was monitored using two types of sensors, polysulphone film and a digital radiation meter. The time periods for sun exposure were computer-derived so as to yield 'safe' exposure times, but these times may have been underestimated. Erythemally effective radiation doses calculated from the sensor readings indicated good agreement between the sensors.

Aged↗