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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,081 records · Page 60Linked to original sources

Evaluation of nucleolar organizer region-associated proteins in breast malignancy.

Nucleolar organizer regions (NORs) have been identified by means of an argyrophilic technique (Ag-NOR) in routinely processed, formalin-fixed paraffin sections of breast lesions. This method, which is novel in histopathology, reveals NORs as black dots in the nuclei of cells, by virtue of the argyrophilia of NOR-associated proteins. The number of Ag-NORs has been thought to be related to cellular activation and has recently been applied to non-Hodgkin's lymphomas and melanocytic skin lesions. It was found in the present study that the total number of Ag-NORs in malignant breast lesions significantly exceeded those of normal breast and benign lesions. The number of clumps of Ag-NORs, however, were not useful discriminators. Neither numbers of total Ag-NORs nor of clumps of Ag-NORs correlate with mitotic counts and it may be that their numbers relate to ploidy. It is suggested that the Ag-NOR technique will find increasing application as an adjunct to diagnostic histopathology.

Adenofibroma↗

Release of proteins from the surface of bovine central nervous system myelin by salts and phospholipases.

Incubation of bovine CNS myelin with phospholipase C from Bacillus cereus under conditions that lead to extensive phospholipid degradation caused 10% of the myelin protein to be released from the membrane. The myelin basic protein (MBP) was a major component of the dissolved protein. Comparable incubations with phospholipase C from Clostridium perfringens, phosphatidylinositol-specific phospholipase C from Staphylococcus aureus, or cabbage phospholipase D removed little MBP. However, concentrations of sodium chloride near 1 M and concentrations of divalent metal ions between 50 and 600 mM released typically 9-12% of the total myelin protein, with MBP again as the predominant component. Repetitive washing with calcium chloride solutions resulted in dissolution of over 90% of the MBP. When myelin was incubated in 1.0 M sodium chloride or 25 mM calcium chloride, the MBP was cleaved largely into two major peptides with apparent molecular weights near 14,000 and 12,000, but with 200 mM or higher concentrations of calcium chloride most of this protein remained intact. With appropriate manipulation of the ionic milieu, it is thus possible to remove most of this extrinsic protein from the myelin surface under relatively mild conditions. The conditions that release the protein suggest that it is held at the membrane surface by ionic interactions.

Animals↗

Structural and segregation analysis of the type II collagen gene (COL2A1) in some heritable chondrodysplasias.

Seventy-seven persons with a variety of heritable chondrodysplasias were screened for gross rearrangements of the structural gene encoding the major cartilage collagen, collagen II. None was found. Segregation of the locus (COL2A1) was studied in 19 pedigrees using three restriction site dimorphisms (shown by PvuII, HindIII, and BamHI) and a length polymorphism as linkage markers. Discordant segregation between COL2A1 and the mutant locus was seen in pedigrees with multiple epiphyseal dysplasia, autosomal recessive spondyloepiphyseal dysplasia tarda, hypochondroplasia, pseudoachondroplasia, diaphyseal aclasis, and trichorhinophalangeal syndrome. One pedigree with diastrophic dysplasia was weakly concordant. Autosomal dominant spondyloepiphyseal dysplasia tarda and metaphyseal chondrodysplasia (type Schmid) were not informative. We conclude that mutations of the collagen II gene are not a common feature of the heritable chondrodysplasias. Since the chondrocyte binding protein, chondrocalcin, is also encoded at COL2A1 our conclusions apply equally to this gene.

Calcium-Binding Proteins↗

Abnormal amino acid analyses obtained from osteogenesis imperfecta dentin.

Amino acid analyses were carried out on dentin proteins obtained from 33 normal teeth and 59 teeth from osteogenesis imperfecta patients. The analyses revealed that in the control teeth approximately 95% of the insoluble dentin fraction was collagen. The majority of the analyses for teeth obtained from the O.I. patients were biochemically abnormal (55 out of 59). Specifically, there was a significant increase in the acidic amino acids, with a corresponding decrease in the basic amino acids. A small group of patients showed double peaks in the histidine, hydroxylysine, and lysine areas of the chromatograms. These results emphasize that despite the fact that the teeth of O.I. patients may appear to be clinically normal, all but four of the teeth examined had abnormal dentin collagen.

Amino Acids↗

Experience with the preoperative invasive measurement of haemodynamic, respiratory and renal function in 100 elderly patients scheduled for major abdominal surgery.

The extent of physiological disturbance in a preoperative population of 100 elderly patients scheduled for elective major surgery was measured. Haemodynamic, respiratory and renal function were evaluated preoperatively in the intensive care unit. Of these patients 13% had serious problems requiring either postponement of the operation (7%) or its cancellation (6%). Cardiac index was 2.2 l/min/m2 or less in 11% of patients; creatinine clearance 50 ml/min or less in 19% of patients; mean blood pressure was equal to or exceeded 120 mmHg in 15% of patients and intrapulmonary shunt equalled or exceeded 15% in 10% of patients. The mean duration of stay in the intensive care unit was four days, including the preoperative day. The logistics of preoperative admission were implemented without undue difficulty.

Abdomen↗

Increased mortality rates in late-life depression.

Physical illness at referral and subsequent mortality were studied in a group of elderly patients with depression, and compared with age/sex-matched controls. The depressed group was significantly less well at first interview, and had a significantly higher 4-year mortality. When the effect of physical illness was controlled, the depressed patients (particularly the men) still had a significantly higher 4-year mortality, suggesting that the greater mortality in the depressed group was not due to differences in physical health alone.

Aged↗

Immunoreactive methionine-enkephalin in cerebrospinal fluid and blood plasma during acute stress in conscious sheep.

The opioid peptide methionine-enkephalin (Met-enkephalin) was measured in plasma and cerebrospinal fluid (CSF) of sheep in which the cisterna magna, carotid artery, and jugular vein were chronically cannulated. Venous blood plasma and CSF were collected before and after stress treatment and in control studies in conscious animals. Plasma and CSF were extracted with octadecylsilica and oxidized, and Met-enkephalin was measured as its Met-sulfoxide derivative by specific RIA. The molecular form of immunoreactive Met-enkephalin was characterized by peptide size exclusion chromatography of an octadecylsilica extract of sheep plasma through Bio-Gel P2, followed by reverse phase liquid chromatography, and was identical to Met-enkephalin and Met-sulfoxide-enkephalin. Insulin-induced hypoglycemia produced an elevation of plasma cortisol and an increase in the plasma concentration of Met-enkephalin. Acute hemorrhage led to an earlier and greater rise in plasma cortisol than that associated with insulin-induced hypoglycemia, but did not increase the concentration of Met-enkephalin in plasma. Neither form of acute stress increased the concentration of Met-enkephalin in CSF. These studies confirm that secretion of Met-enkephalin into blood can be dissociated from stimulation of the pituitary-adrenocortical system. They also show that circulating Met-enkephalin is elevated in conscious sheep during acute hypoglycemic stress, but plasma Met-enkephalin is unlikely to exert effects on the opiate receptors of periaqueductal or spinal nociceptive neurons under these conditions, since it does not enter cerebrospinal fluid in significant amounts.

Animals↗

Secretion of beta-endorphin into the maternal circulation by uteroplacental tissues in response to hypoglycaemic stress.

The placenta has been shown to contain ACTH and beta-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine beta-endorphin (o beta-EP) were measured by radioimmunoassay. Concentrations of o beta-EP rose in both vessels by 60 min after insulin. The peak concentrations of o beta-EP (pmol/l) were 122 +/- 29 (mean +/- SEM, n = 8) in the UV and 96 +/- 24 (n = 9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of o beta-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of o beta-EP were significantly higher in the UV than FA (P less than 0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting beta-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.

Animals↗

Secretion of corticotropin-releasing hormone by superfused human placental fragments.

Corticotropin-releasing hormone (CRH) immunoreactivity (IR) is present in the blood of women in the 3rd trimester of pregnancy and in placental extracts. We have used a placental fragment superfusion system to investigate the release of CRH from fresh placental tissue. Fragments of normal term placenta were mixed with Biogel P2, packed into minicolumns and superfused with carbogen-gassed Earles buffer at 37 degrees C. The rheology of the superfusion system was determined and the oxygen consumption of the superfused placental fragments indicated viability of the tissue preparation over a 5-hour time span. CRH IR in the eluate was measured by radioimmunoassay (RIA) using the 41 residue synthetic peptide human, rat CRH-41 (h, r CRH-41) as the standard, 125I labelled Tyr- h, r CRH as the tracer and rabbit anti-ovine CRH as the antibody. The sensitivity of the assay is 2 pM. Size exclusion chromatography on Sephadex G-50 of the placental column eluate displayed one major peak of CRH IR which co-eluted with that of h, r CRH. Placental fragment superfusate displayed potent CRH bioactivity as assessed by beta-endorphin secretion from ovine pituitary cells. Replacing the superfusing medium of the placental fragments with 45 mM KCl resulted in a prompt increase in the release of CRH IR. These results indicate that placental cells in vitro secrete a molecule of similar molecular weight, immunoreactivity and bioactivity to h, r CRH and that the rate of secretion may be regulated.

Animals↗

Quality assurance in equipment ordering for the spinal cord-injured client.

Occupational therapy for spinal cord-injured clients is based on training in the use of adapted techniques and adapted equipment to optimize functioning. Two factors, the need for equipment to enhance the client's potential and the demand for cost containment in equipment ordering, spurred a quality assurance study of equipment ordering. Through a follow-up survey of persons who had received equipment while they were patients of the New England Regional Spinal Cord Injury Center, suspected problems were identified and defined. A plan was formulated and implemented to resolve the problems; then the outcomes of this plan were evaluated by a telephone survey 1 year later. This quality assurance study helped establish accountability for cost containment in equipment ordering based on the client's perceived need, the client's level of spinal cord injury, equipment durability, and the timeliness of ordering.

Cost Control↗

High prevalence of genital tract papillomavirus infection in female adolescents.

To investigate clinical condyloma, abnormal cervical cytologic findings, and evidence of human papillomavirus infections, 89 adolescent girls were examined. Cellular DNAs extracted from exfoliated cervical cells were examined for human papillomavirus genomic sequences by Southern transfer hybridization using 32P-labeled human papillomavirus DNA probes. Human papillomavirus sequences were detected in 12 (13%) young women, abnormal cytologic specimens in 21 (24%), and vulvar condylomas in 12 (13%). The human papillomavirus types identified included HPV-6/11 (four instances), which is known to be associated with benign lesions, and HPV-16, -18, and -31 (eight instances) which are considered to have oncogenic potential. Two young women were infected with both HPV-16 and -31. Human papillomavirus sequences were found in 48% of the young women with abnormal cytologic findings and in 3% of patients with normal cytologic findings (P less than .0001). Condylomatous changes in the cervical smear were associated with the presence of HPV-6/11 and mild dysplasia with the presence of HPV-16, -18, and -31. The presence of vulvar condylomas correlated with condylomatous changes in the cervical smear and with the recovery of HPV-6/11 from the cervical epithelium. The results indicate that the prevalence of human papillomavirus infections in this population is high and that a majority of the infections are with viruses associated with lower genital tract malignancies.

Adolescent↗

Clinical evaluation of a yeast recombinant hepatitis B vaccine in healthy hospital staff in Singapore.

A yeast recombinant hepatitis B vaccine (subtype adw), derived from purification of HBsAg particles, expressed in the yeast Saccharomyces cerevisiae which contained the gene for HBsAg, was evaluated in 31 healthy adult hospital staff members in Singapore. Each subject received a 10 mcg dose of vaccine intramuscularly at 0, 1 and 6 months. One month after the first two injections of vaccine the seroconversion rate (defined as greater than or equal to 2.7 mIU/ml) was 90%. Two months after the third injection 100% of participants had anti-HBs levels higher than 2.7 mIU/ml and 97% had titers of anti-HBs greater than 10 mIU/ml. The geometric mean titer (GMT) of anti-HBs levels at 2, 3, 6, 8 and 12 months were 21.9, 38.6, 57.6, 1253.4 and 354.1 mIU/ml, respectively. All clinical complaints were mild and transient. They consisted of mild soreness at the injection site, transient fever and headache. There was no correlation between the presence of antibodies to S. cerevisiae with any allergic manifestations. The vaccine was safe and immunogenic for staff exposed to an infection risk and should now be widely used in the extension of hepatitis B immunization programs.

Ethnicity↗

Alcohol abuse.

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Ethanol↗