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Biomedical subjects

D Donaldson

Publications and source records attributed to D Donaldson.

At least 19 recordsLinked to original sources
PubMed1992

Hyperglycemia suppresses c-fos mRNA expression following transient cerebral ischemia in gerbils.

The c-fos proto-oncogene is activated by transient cerebral ischemia. This activation may signify a specific genetic response to ischemia affecting tolerance to ischemia and ultimate cell survival. Hyperglycemia, which enhances brain injury from transient ischemia, was studied for its effects on this gene system in gerbils by measuring c-fos mRNA 2 h after 20 min of bilateral carotid artery occlusion. Brain c-fos mRNA was increased by ischemia (11.7 +/- 5.0, p less than or equal to 0.05, fold increase) compared to nonischemic controls (1.0 +/- 1.3). Pretreatment with 1 g/kg of glucose partially reduced postischemic c-fos mRNA (6.3 +/- 1.6, p less than or equal to 0.05) while 4 g/kg of glucose completely suppressed postischemic c-fos expression (0.7 +/- 0.3, p less than or equal to 0.05). These data indicate that hyperglycemia suppresses normal postischemic gene expression and suggest the possibility that such suppression is a predictor or even a contributor to hyperglycemia-enhanced ischemic brain damage.

Animals↗
PubMed1992

Purification and biochemical characterisation of human and murine stem cell inhibitors (SCI).

We have recently characterised an inhibitor of haemopoietic stem cell proliferation (SCI/MIP-1 alpha) and report here on its purification and initial biological and biochemical characterisation. The activity can be detected by direct addition to the CFU-A stem cell assay and this simple test for inhibitory activity has greatly facilitated the purification of the molecule. The purification involves a combination of Mono Q ion exchange chromatography, heparin-sepharose affinity chromatography and Blue Sepharose affinity chromatography. The purified stem cell inhibitor is an 8 kD peptide which is identical to the previously described peptide macrophage inflammatory protein 1 alpha. The peptide has a natural tendency to form large self-aggregates and appears, in physiological buffers, to have a native molecular weight of around 90 kD. SCI is a heat stable, protease sensitive protein which is half maximally active at between 10 and 25 pM in the CFU-A assay. The self-aggregates can be disrupted by dilute solutions of acetic acid and it appears that disruption increases the specific activity of SCI preparations. We also report the characterisation of the human homologue of the stem cell inhibitor (human SCI/MIP-1 alpha) which is 74% identical to murine MIP-1 alpha and which shares all the above features of the murine inhibitor.

Animals↗
PubMed1991

Isoenzymes of alkaline phosphatase in epileptic patients receiving carbamazepine monotherapy.

The effects of carbamazepine monotherapy were investigated in 20 female and 21 male epileptic patients to determine whether treatment would induce an increase in serum alkaline phosphatase (ALP) activity, a known effect of many anticonvulsant drugs. Serum total ALP activity was increased in nine out of the 41 patients (22%), serum bone ALP activity was increased in 10 (24%), and serum non-bone ALP activity was increased in three (7%). There was no significant difference when the mean of the patients' serum total ALP was compared with that of the controls. Twenty per cent of the patients with increased serum bone ALP had normal serum total ALP, indicating that increased serum bone isoenzyme activity may precede an increase in the total enzyme activity. This should be considered when interpreting results of increased total ALP in epileptic patients.

Adult↗
PubMed1991

Relationships between requests for psychiatric consultations and psychiatric diagnoses in long-term-care facilities.

OBJECTIVE: The authors' objective was to investigate reasons for referral of elderly nursing home residents for psychiatric consultation and the relationship of these reasons for referral to psychiatric diagnoses. METHOD: They examined 197 nursing home residents consecutively referred to a consulting team in a university-affiliated mental health center. These patients represented all patients evaluated by the consulting team at six nursing homes over a 2-year period (Sept. 1, 1984, through Aug. 30, 1986). RESULTS: Reasons for referral were diverse but fell into seven broad clusters: behavioral problems; mood-related problems; consultations requested by involuntary treatment services, patients, physicians, or other referring agencies; psychotic features; physical signs; impaired activities of daily living; and other. Behavioral problems were most commonly cited and tended to be associated with dementia diagnoses. Mood-related reasons for referral were most strongly associated with diagnoses of affective disorders, and diagnoses of schizophrenia and adjustment disorder were each associated with two or more reasons for referral. However, reasons for referral were distributed widely across diagnostic groups and were relatively weak predictors of diagnoses. CONCLUSIONS: The results illustrate the variety of problems for which nursing home staff are willing to seek psychiatric consultation but emphasize the need for professional psychiatric evaluation to establish a diagnostic base on which treatment interventions can be built.

Adjustment Disorders↗
PubMed1991

The cost of rural health services in Papua New Guinea.

In 1988 a countrywide study was conducted on the costs of rural health services in Papua New Guinea. 16% of all health centres and subcentres were surveyed. Information was collected on physical facilities, recurrent costs, staff time allocation, service outputs and quality of services. Wide variation was found in the costs of rural health facilities overall, and significant differences were found between the costs and outputs of health centres and subcentres. Average levels of service output were found to be similar at church and government facilities but average levels of utilization by the population were higher at church facilities. Despite government policy on extension of preventive health care, a strong emphasis was found on curative care. Many facilities were found to have significant excess bed capacity. Recurrent financing for transportation and maintenance was found to be inadequate.

Cost Allocation↗
PubMed1990

Identification and characterization of an inhibitor of haemopoietic stem cell proliferation.

The haemopoietic system has three main compartments: multi-potential stem cells, intermediate stage progenitor cells and mature cells. The availability of simple reproducible culture systems has made possible the characterization and purification of regulators of the progenitor cells, including colony-stimulating factors and interleukins. In contrast, our knowledge of the regulators involved in the control of stem cell proliferation is limited. The steady-state quiescent status of the haemopoietic stem cell compartment is thought to be controlled by locally acting regulatory elements present in the stromal microenvironment, but their purification has been hampered by the lack of suitable culture systems. We have recently developed a novel in vitro colony assay that detects a primitive cell (CFU-A) which has similar proliferative characteristics, in normal and regenerating bone marrow, to the CFU-S (haemopoietic stem cells, as defined by the spleen colony assay) and which responds to CFU-S-specific proliferation regulators. We have now used this assay to purify to homogeneity a macrophage-derived reversible inhibitor of haemopoietic stem cell proliferation (stem cell inhibitor, SCI). Antibody inhibition and sequence data indicate that SCI is identical to a previously described cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and that SCI/MIP-1 alpha is functionally and antigenically identical to the CFU-S inhibitory activity obtained from primary cultures of normal bone marrow cells. The biological activities of SCI/MIP-1 alpha suggest that it is a primary negative regulator of stem cell proliferation and that it has important therapeutic applications in protecting haemopoietic stem cells from damage during cytotoxic therapies for cancer.

Amino Acid Sequence↗
PubMed1990

Focal cerebral infarction in cats in the presence of hyperglycemia and increased insulin.

Although it has been well established that hyperglycemia increases cerebral damage following transient cerebral ischemia, its effect on permanent focal ischemia is controversial. We hypothesized that other factors associated with hyperglycemia, such as plasma insulin, may alter the brain's response to hyperglycemia. The objective of this study was to determine if hyperglycemia changes infarction size following 8 hr of middle cerebral artery occlusion in the anesthetized cat and to examine if changes in plasma insulin levels alter hyperglycemia's effects. Infarct size in hyperglycemic cats with increased plasma insulin (38.3 +/- 8.4, mean +/- SE) or in hyperglycemic cats without increased plasma insulin (30.5 +/- 7.6%) was not significantly different from that of ischemic controls (33.8 +/- 2.8%). However, the variability in infarct size tended to be greater (P = 0.0647) among all hyperglycemic cats compared to control animals. The source of the variability is unknown, but this observation is dependent on the exact nature of the focal ischemic insult (i.e., degree of collateral blood supply) and that this effect may vary greatly from individual to individual within a population.

Analysis of Variance↗
PubMed1990

Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site.

Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63Ni2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation (since proalbumin contains adjacent Arg residues at -1 and -2) or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala----Thr. This introduces an Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg----Cys. This introduces a prepro sequence, Met-Lys-Trp-Val-Thr-Phe-Ile-Ser-Leu-Leu-Phe-Leu-Phe-Ser-Ser-Ala-Tyr- Ser-Arg-Gly-Val-Phe-Cys-Arg (cf.-Tyr-Ser-Arg-Gly-Val-Phe-Arg-Arg- in normal human pre-proalbumin). We propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase.

Alanine↗
PubMed1990

Relationship between plasma glucose, brain lactate, and intracellular pH during cerebral ischemia in gerbils.

The dose-response relation between plasma glucose and brain lactate and the relation of these parameters to intracellular pH during severe cerebral ischemia have not been well characterized over a wide range of plasma glucose levels. Experiments to delineate these relations in the gerbil model of global ischemia were performed by using phosphorus-31 nuclear magnetic resonance spectroscopy to measure intracellular pH and a new method to measure brain lactate. Ischemia increased final brain lactate linearly 4 mumol/g for every 100 mg/dl increase in plasma glucose up to 650 mg/dl (p = 0.0001, r2 = 0.9); beyond 650 mg/dl, saturation of the glucose transport-glycolysis system occurred. Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 mumol/g; below 17 mumol/g, intracellular pH remained stable at 6.8-6.9, whereas above 22 mumol/g, intracellular pH decreased maximally to about 6.2. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 mumol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage.

Analysis of Variance↗
PubMed1989

The mechanisms of nitrous oxide scavenging devices.

A recent publication discussing the concern with nitrous oxide pollution in dental offices and the methods available to reduce this risk aroused interest in scavenging systems. This is the first in a series of three articles and will explain the mechanisms of the nitrous oxide systems available. The second describes the testing of these systems under ideal conditions and the third will assess their efficiency in various dental offices and the factors which were found to detract from that efficiency.

Air Pollution↗
PubMed1989

A comparison of the effectiveness of nitrous oxide scavenging devices.

Four nitrous oxide scavenging systems were tested for their efficiency under ideal standardized conditions. The volunteers received 35% nitrous oxide for 20 minutes and the levels of nitrous oxide recorded and averaged every five minutes. No density was carried out. All four systems achieved levels below 30 parts per million. With the recommended limit for nitrous oxide levels in dental operatory being 50 parts per million (ppm) rather than the several thousand ppm reached without scavenging, it is necessary to ensure that the scavenging devices available are capable of achieving this level. To do so under normal dental operating conditions provides many variables, such as the type of procedure carried out, movement by the patient, ventilation efficiency of the operatory, type of mouth pack utilized etc. This investigation was therefore designed to eliminate all operator and procedure variabilities. Each system was evaluated under ideal identical conditions and with no actual treatment being carried out.

Air Pollutants, Occupational↗
PubMed1989

The efficiency of nitrous oxide scavenging devices in dental offices.

Five scavenging systems were installed in 10 dental office and the levels of nitrous oxide were closely monitored for each. While the readings were higher than the previous non-clinical study, all appeared to be reasonably efficient. The various factors which caused increases in background levels were also recorded in the investigation.

Air Pollutants, Occupational↗
PubMed1979

Specificity of chromatin transcription in vitro. Anomalies due to RNA-dependent RNA synthesis.

In the presence of Mn2+, globin mRNA can be transcribed into a partial RNA copy by Escherichia coli RNA polymerase. This process also occurs when the mRNA is transcribed together with chromatin. A fraction, at least, of the newly synthesized RNA copy (anti-globin RNA) can serve as a template for the synthesis of globin sequences of the same polarity as the original mRNA. This process is sufficient to explain the specific synthesis of a subset of the globin RNA on mouse foetal liver chromatin. It also accounts for the synthesis of double-stranded RNA sequence by E. coli RNA polymerase, on chromatin as well as on pure mRNA. Results are presented suggesting that the poly(A) tract of the mRNA could be preferentially transcribed. In the presence of Mg2+, the RNA-dependent transcription is strongly inhibited, as well as the synthesis of double-stranded RNA. Under these conditions, the transcription on chromatin appears to be largely DNA dependent, and the synthesis of globin sequences is completely asymmetric. Spermine (0.3 mM) seems to improve the specificity of transcription. The transcription of chromatin in vitro is thus largely dependent on the nature of the divalent cation present in the in the incubation mixture.

Animals↗
PubMed1979

Vitamin A, zinc and lung cancer.

Serum vitamin A concentration were measured in 26 newly diagnosed lung-cancer patients and found to be significantly lower than those of patients of similar age with either non-malignant lung or non-lung diseases. The levels of vitamin A in the lung-cancer patients, but not in the controls, were significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver.

Aged↗