Intrathymic transplantation of rat perinatal islets, devoid of class II bearing cells, does not induce donor-specific tolerance.
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Animals↗
Biomedical subjects
D Donaldson
Publications and source records attributed to D Donaldson.
A comparison of the effects of EMLA cream and topical 5% lidocaine on discomfort during gingival probing.
This investigation compared the use of a 5% eutectic mixture of local anesthetics (EMLA) cream to a "standard" intraoral topical anesthetic (5% lidocaine) as a means of anesthetizing the gingival sulcus in a double-blind, split-mouth study with human volunteers. A 5-min application of EMLA in a customized intraoral splint resulted in a significant increase in the depth of probing of the gingival sulcus without discomfort compared to a similar application of 5% lidocaine. Following application of EMLA, the pain-free probing depth measured at three sites in the upper premolar region increased by a mean total of 2.8 mm compared to an increase of 1.9 mm with lidocaine. This study suggests EMLA may be advantageous in providing periodontal anesthesia where manipulation of the gingiva is necessary.
Administration, Topical↗
Synergistic interaction between interleukin-12 and steel factor in support of proliferation of murine lymphohematopoietic progenitors in culture.
We have investigated the effects of interleukin (IL)-12 (natural killer cell stimulatory factor/cytotoxic lymphocyte maturation factor) on the proliferation of murine myeloid and lymphohematopoietic progenitors in methylcellulose culture. In the presence of erythropoietin (Ep), IL-12 alone failed to support colony formation by mononuclear and enriched marrow cells of normal mice. Steel factor (SF) alone supported primarily formation of granulocyte/macrophage (GM) colony formation. However, the combination of the two cytokines yielded a significant number of multilineage colonies. When tested on marrow cells from 5-fluorouracil (5-FU)-treated mice, the combination of IL-12 and SF, but not the single factors, was effective in support of formation of various types of colonies. Approximately 25% of these colonies yielded pre-B-cell colonies when replated in secondary culture containing SF and IL-7, indicating that IL-12 can interact with SF in supporting the development of primitive lymphohematopoietic progenitors. These results demonstrate that IL-12, a cytokine believed to be involved in the development of cell-mediated immune responses, has a wider range of activity, including committed myeloid and multipotent lymphohematopoietic progenitors.
Animals↗
Differences in nigral neuron number and sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57/bl and CD-1 mice.
The present study demonstrates that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes significantly greater reductions in striatal dopamine levels in C57/bl mice than in CD-1 mice, thus confirming a greater sensitivity of the C57/bl mice to MPTP. To determine the possible reasons for this difference in MPTP sensitivity between these two mouse strains, we have compared both the organization and the number of substantia nigra (SN) neurons, the primary target of MPTP, in C57/bl and in CD-1 mice using immunostaining for tyrosine hydroxylase (TH) and calbindin-D28k (calbindin). In saline-injected animals, there is a significantly lower number of SN TH-positive and calbindin-positive neurons in C57/bl than CD-1 mice; no significant differences in the numbers of these neurons are found in the ventral tegmental area between the two strains. In MPTP-injected animals, the reductions in SN TH-positive neurons are significantly greater in C57/bl than in CD-1 mice. In contrast, MPTP does not cause any significant changes in the numbers of SN calbindin-positive neurons in either strain. The present study shows that C57/bl mice which have fewer SN TH-positive neurons are more sensitive to MPTP-induced toxicity than CD-1 mice. This observation suggests a possible inverse relationship between SN TH-positive neuron number and MPTP sensitivity. If correct, this hypothesis may be of major importance for Parkinson's disease since it is suggested that individuals at risk of developing this neurodegenerative disorder may have lower numbers of SN TH-positive neurons to start with. The present study also shows that SN calbindin-positive neurons are spared following MPTP administration. However, the observed difference in SN calbindin-positive neuron numbers does not account for the differential sensitivity to MPTP between these two mouse strains.
3,4-Dihydroxyphenylacetic Acid↗
Regional levels of free fatty acids and Evans blue extravasation after experimental brain injury.
The recently developed controlled cortical-impact (CCI) model of brain injury in rats serves as an excellent tool to understand some of the neurochemical mechanisms mediating the pathophysiology of traumatic brain injury. In this study, rats were subjected to lateral CCI brain injury of low-grade severity. Their brains were frozen in situ at various times after injury to measure regional levels of free fatty acids. Tissue total free fatty acids at the injury site within the left cortex were increased at 30 min, 2.5 h, and 24 h postinjury. In injured animals, increases in stearic and arachidonic acids were slightly greater than those in palmitic and oleic acids. The levels of total free fatty acids in the cortex adjacent to the injury site were also increased in injured animals at 2.5 h and 24 h after injury (p < 0.05). Only stearic and arachidonic acids were observed to be significantly increased (p < 0.05) in the adjacent cortex of injured animals at all times after injury. Although no significant increases in total free fatty acids were observed in the left hippocampus adjacent to the injury site, stearate and arachidonate concentrations were increased at 30 min and 2.5 h after injury (p < 0.05). Extravasation of Evans blue was found to be significantly increased in the ipsilateral cortex of injured animals at 30 min and 10 h after brain injury. These results indicate the degradation of membrane phospholipids and blood-brain barrier breakdown in the ipsilateral cortex after lateral CCI brain injury. These results also suggest that arachidonic acid and its metabolites may play a role as a mediator in the blood-brain barrier breakdown associated with cortical impact brain injury in rats.
Animals↗
The use of epinephrine in dentistry.
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Anaphylaxis↗
Synergistic effects of interleukin-11 with other growth factors on the expansion of murine hematopoietic progenitors and maintenance of stem cells in liquid culture.
The effect of interleukin-11 (IL-11), alone and in combination with other hematopoietic growth factors, was studied in liquid suspension cultures of murine bone marrow. Stem and progenitor cell contents of input bone marrow 2 days after 5-fluorouracil (5-FU) treatment (FU2dBM) and lineage-depleted, Sca-1-positive FU2dBM (Lin-Sca+Fu2dBM) were compared with output values obtained after 6 days in different growth factor combinations. Stem and progenitor cell recoveries were measured by long-term in vivo competitive repopulation, spleen colony-forming unit (CFU-S), and in vitro limiting dilution long-term bone marrow culture (cobblestone area-forming cell [CAFC]) assays. IL-11, IL-3, IL-6, and Steel factor (SF) were tested separately and in combinations of two, three, and four factors. IL-11 was incapable of maintaining the survival of stem or progenitor cells as a single agent but synergized with either IL-3 or SF to expand progenitor cell output in cultures of FU2dBM. IL-11 greatly enhanced progenitor cell expansion from FU2dBM when added to two- and three-factor combinations of SF, IL-3, and IL-6. The recovery of long-term repopulating ability was enhanced four-fold by incubation in SF plus IL-11 compared to SF alone. IL-11 in combination with SF, IL-3, and IL-6 stimulated a 24,000-fold expansion of progenitor cells from stem cell-enriched Lin-Sca+FU2dBM. Overall, the results indicate that IL-11 is a potent synergistic factor for stem cell proliferation and expansion of progenitors in liquid culture.
Animals↗
Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo.
A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5-FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst-forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP-1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors.
Animals↗
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.
Amino Acid Sequence↗
Physical mapping of chromosome 21.
Chromosome 21, the smallest human chromosome, has been the subject of intense study because it is the chromosome which, when present in an extra copy, leads to Down Syndrome. Moreover, there are genes important for several human genetic disorders on this chromosome, and a significant number of individuals with aneuploidies of regions of the chromosome have been identified. A high fidelity, high resolution physical map of chromosome 21 will be of immense value in generating an accurate genotype/phenotype map of the chromosome and in identifying and isolating genes on the chromosome which may be responsible for various human genetic disorders. Here we describe the current status of our attempts to create such a map. This includes attempts to integrate various physical mapping approaches. Progress towards construction of a minimal set of yeast artificial chromosomes (YACs) spanning the chromosome is described.
Chromosome Mapping↗
A genetic linkage map of chromosome 21: a look at meiotic phenomena.
We have developed a genetic linkage map of chromosome 21 using 17 microsatellite marker polymorphisms. The markers span virtually the entire length of 21q, and define a sex-equal map of 56 cM. Extensive error checking has been used to provide an accurate map. All recombination events have been identified, allowing us to place within a small interval any new markers by genotyping only a few critical individuals. The resulting segregation data has been examined for several meiotic phenomena, including sex differences in recombination, age differences in recombination, interference, and segregation distortion.
Alzheimer Disease↗
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↗
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↗
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↗
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↗
Serum gamma glutamyl transferase activities in epileptic patients receiving carbamazepine monotherapy.
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Adolescent↗
Cholesterol screening--is it desirable?
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Cholesterol↗
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↗