Detection of Mycobacterium bovis in bovine blood by combined PCR and DNA probe methods.
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Animals↗
Biomedical subjects
T Smith
Publications and source records attributed to T Smith.
Distinct effects of bFGF and PDGF on oligodendrocyte progenitor cells.
We have compared the effects of platelet-derived (PDGF) and basic fibroblast (bFGF) growth factors on the shape, migration, and differentiation of oligodendrocyte progenitor cells, the precursors of myelin-forming cells in the CNS. In the presence of bFGF, oligodendrocyte progenitors purified from rat neonatal brain cultures were stellate, non-motile, and had a morphological complexity of 1.26 +/- 0.03 as measured by fractal dimension (D). These cells expressed transcripts encoding the POU-homeodomain transcription factor Oct-6, but not myelin genes. Upon addition of PDGF, bFGF-treated cells became motile and twofold less complex in shape (D = 1.19 +/- 0.03). These changes occurred within 6 +/- 4 h and were dependent on de novo transcription and translation, but not DNA synthesis. Upon removal of PDGF the cells reverted to their stellate shape (D = 1.26). Removal of both bFGF and PDGF resulted in oligodendrocyte differentiation after 3 days, with a fourfold increase in complexity of shape (D = 1.55 +/- 0.08), loss of Oct-6 transcripts, and gain of myelin transcripts. Thus PDGF is both necessary and sufficient to induce a motile state in progenitor cells growing in the presence of bFGF. Together with our previous data (McKinnon et al.: Neuron 5:603, 1990), our results suggest that bFGF and PDGF may control distinct phases of proliferation and migration of oligodendrocyte progenitor cells in vivo.
Animals↗
Representational-momentum effects in the cerebral hemispheres.
On each trial, after three squares of different sizes (inducing display) were sequentially presented at central fixation, a target square was briefly lateralized to the right or left hemisphere (RH or LH) of 24 normal right-handed males. Subjects determined whether or not the target differed in size from the third inducing square. Half of the targets that differed were consistent with size changes in the inducing display (e.g., a target smaller than the third square in an inducing display presented in a large-to-small order) and half were inconsistent. Three retention intervals (RIs) between offset of third inducing square and onset of target were used. At the shortest RI, error-rate differences in responding to consistent vs. inconsistent targets, i.e., representational-momentum (RM) effects, were larger in the RH than in the LH, and RM effects in the RH, but not in the LH, were affected by RI.
Adult↗
Bone remodeling in hip fracture.
Hip fracture incidence has shown strong upward secular trends in many societies with wide differences in age adjusted incidence between nations. Falls and reduced physical activity have emerged as the strongest risk factors in epidemiological studies, while clinical investigations have pointed to secondary hyperparathyroidism as an important candidate cause of the loss of femoral cortical bone in old age. Until recently there have been few studies performed directly on the region of interest in the proximal femur. Non-invasive methodology using 85Sr has now been developed by our group for measuring bone formation and (with concurrent serial DXA densitometry) resorption in the femoral neck. Bone turnover averaged about 8% annually in controls. A group of younger cases of femoral fracture showed similar indices of total and regional bone formation to a control group; but their resorption was higher. To further investigate this, a femoral neck bone biopsy technique has been developed which can be applied to fracture cases treated by arthroplasty. Preliminary studies have established that the anatomical asymmetry of the neck in cross-section is considerable and imposes restraints on the interpretation of smaller or incomplete femur biopsies. Prospects are quite good that, in the absence of tetracycline pre-labeling, mineralization can be studied by assessment of alkaline phosphatase-positive surfaces in cryostat sections. Moreover, such sections will permit study of other anatomically localized metabolic activities as well as antigen expression and osteocyte viability. Candidate mechanisms for the regional decline in bone quality as well as bone mass in subjects suffering hip fracture can now be investigated more effectively.
Biomarkers↗
Lactate dehydrogenase levels during MACOP-B chemotherapy for non-Hodgkin's lymphoma.
Lactate dehydrogenase (LD) levels rose consistently during MACOP-B chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma (NHL). Levels peaked at week nine and fell to normal within six weeks of completion of therapy. Isoenzyme patterns, studied prospectively in seven patients, showed a parallel rise in LD1 and LD2 suggesting a source other than tumour tissue for the rise in total LD. In the absence of evidence of myocardial or renal damage, haematopoietic tissue was the most likely source. With no evidence of haemolysis, normal serum levels of vitamin B12 and folate and normal red cell folate, dyserythropoiesis was considered to be the underlying mechanism. A rising mean corpuscular volume further reinforced this suggestion. Intensive use of methotrexate along with co-trimoxazole as prophylaxis against pneumoycystis carinii is considered the most likely cause of marrow dysfunction. Failure to recognise that rising LD levels during such therapy is treatment-related, rather than of tumour origin, may lead to inappropriate change or abandonment of therapy.
Adult↗
Absence of seasonal variation in malaria parasitaemia in an area of intense seasonal transmission.
Parasitological surveys carried out in two villages of the Kilombero district of Tanzania indicated a very high prevalence of Plasmodium falciparum parasitaemia throughout the year (all ages mean prevalence = 69.2%) and a low, unstable prevalence of P. malariae (all ages mean prevalence = 4.5%). Fevers (temperature > or = 37.5 degrees C) in both children and adults showed irregular changes in prevalence over time, but there was no seasonal pattern. Neither was there seasonal variation in either P. falciparum parasite prevalence or parasite densities. This was despite marked seasonality in vectors caught in CDC light-traps and in estimated sporozoite inoculations determined by ELISA. The estimated mean annual inoculation rate was extremely high, over 300 infectious bites per person per year, the main vectors being members of the A. gambiae complex and Anopheles funestus. There was considerable variation between houses but even in houses with relatively low mosquito numbers the inoculation rate was sufficient to maintain a maximal P. falciparum prevalence. Heterogeneities in exposure cannot explain why the parasite prevalence is not always 100%. In areas of such high transmission, parasitaemias are likely to be determined mainly by the interaction of schizogony and anti-blood stage immunity, since parasites arising from new inoculations generally comprise only a small proportion of the total in the circulation. In any one individual, this will lead to periodic fluctuations in levels of parasitaemia. These are unlikely to show a close relationship to either seasonal variation in inoculations or to differences between households in the local inoculation rate.
Adolescent↗
Risk of disease progression in asymptomatic multiple myeloma.
PURPOSE: In recent years, increasing numbers of patients with asymptomatic multiple myeloma have been diagnosed by chance and followed without any therapy. Those at risk for early or late disease progression should be distinguished in order to prevent complications. This study defined prognostic factors that would predict the need for early treatment. PATIENTS AND METHODS: We followed 95 patients with asymptomatic multiple myeloma without chemotherapy between 1974 and 1991. Magnetic resonance imaging (MRI) of the spine was conducted in 23% of patients with normal radiographs. An increase in serum myeloma protein to more than 50 g/L or new lytic bone lesions justified the institution of chemotherapy. Response to treatment and survival were assessed, and prognostic factors were defined for early or late disease progression by standard techniques. RESULTS: The median time to progression in all patients was 26 months. The 25 patients with either a lytic bone lesion, or both serum peak greater than 30 g/L and Bence Jones proteinuria, had the shortest median time to progression of 10 months; the 27 patients without any harmful factor remained stable for a median of 61 months. MRI confirmed bone or marrow disease in half of the patients with normal radiographs and may assist in the prognostic staging. Despite the markedly different times of disease stability, the response rates and survival after chemotherapy were similar for all groups of patients. CONCLUSION: Among asymptomatic patients with multiple myeloma, the extent of disease at diagnosis and the subsequent rate of disease evolution were major factors in the total survival time. These patients are a markedly heterogeneous group who may benefit from different approaches to treatment according to defined risk factors.
Female↗
Efficient pattern comparative method for selecting functionally important motifs in protein sequences: application to zinc enzymes.
We have developed a pattern comparative method for identifying functionally important motifs in protein sequences. The essence of most standard pattern comparative methods is a comparison of patterns occurring in different sequences using an optimized weight matrix. In contrast, our approach is based on a measure of similarity among all the candidate motifs within the same sequence. This method may prove to be particularly efficient for proteins encoding the same biochemical function, but with different primary sequences, and when tertiary structure information from one or more sequences is available. We have applied this method to a special class of zinc-binding enzymes known as endopeptidases.
Amino Acid Sequence↗
Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children.
Rates of acquisition and mean duration of nasal carriage of different serotypes of Streptococcus pneumoniae have been estimated by fitting a stochastic model to longitudinal carriage data in children from Papua New Guinea. Immunogenicity and two indices of relative invasiveness were determined for each serotype. Immunogenic serotypes were less frequently acquired and were carried for shorter periods, but no relationship between immunogenicity and invasiveness was apparent using either index of invasiveness. Frequent invasion was associated with a high acquisition rate and high frequency and prolonged duration of carriage. Carriage studies can provide a broad indication of which serotypes cause invasive disease but not the proportion of disease due to individual serotypes; some serotypes which cause invasive disease (e.g. serotype 46) are not found even in extensive carriage studies. The antibiotic resistance of carriage organisms, however, does approximate the resistance patterns of invasive organisms and thus may be used to monitor changing patterns of antimicrobial susceptibility in the community.
Antibodies, Bacterial↗
LIS is more.
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1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Glycosylation of yeast microsomal proteins: preliminary characterization studies.
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Electrophoresis, Polyacrylamide Gel↗
Plasma lipid physical properties in swine fed margarine or butter in relation to dietary magnesium intake.
Plasma lipids obtained from swine which had been fed butter or margarine at two dietary magnesium (Mg) levels indicated that the level of dietary Mg was more significant to plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels than was the presence of butter or margarine. At 270 mg Mg/kg, which is considered adequate for swine, there was a significant difference in the plasma TC between swine fed margarine and those fed butterfat (105 and 126 mg %, respectively). Plasma LDL-C was higher in swine fed butter than in those fed margarine (88 and 71 mg %, respectively). In swine fed an additional 247 mg Mg/kg, however, there was no significant difference in plasma TC between those fed margarine or butter. Although at 247 mg Mg/kg, however, there was no significant difference in plasma TC between those fed margarine or butter. Although at 247 mg Mg/kg plasma LDL-C was higher in swine fed margarine and HDL-C was higher in those fed butter, there were no significant differences in the order parameters of LDL and HDL. Studies in which the influences of dietary fats on plasma cholesterol were first noted were carried out on liquid diets deficient in Mg. Mg, a cofactor in the enzymes involved in desaturation of saturated fatty acids, is also necessary in desaturation of linoleic to arachidonic acid.
Animals↗
Ganciclovir for the treatment of cytomegalovirus pneumonia in an immunocompetent host.
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Adult↗
Hypothermic acid-base management does not affect cerebral metabolic rate for oxygen at 27 degrees C. A study during cardiopulmonary bypass in rabbits.
BACKGROUND: It has been contended that, during cardiopulmonary bypass at 27 degrees C, pH-stat management decreases cerebral metabolic rate for oxygen (CMRO2) more than alpha-stat management. In contrast, other studies have not found CMRO2 to differ between techniques. Using each animal as its own control, the authors assessed the effect of alpha-stat versus pH-stat management of CMRO2, cerebral blood flow (CBF), and brain oxygen extraction during cardiopulmonary bypass at 27 degrees C. METHODS: Fourteen New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent cardiopulmonary bypass at 27 degrees C (membrane oxygenator, centrifugal pump, and bifemoral arterial perfusion). Group 1 animals (n = 7) had alpha-stat management for the initial 65-70 min of bypass, and were then changed to pH-stat management for the remaining 30 min of bypass. Group 2 animals (n = 7) had pH-stat management for the initial 65-70 min of bypass, and were then changed to alpha-stat management for the remaining 30 min. Measurement of CBF (radiolabeled microspheres), CMRO2 (CBF x brain arterial-venous oxygen content difference), brain temperature, systemic hemodynamics, and arterial blood gases were made in each animal under both alpha-stat and pH-stat conditions. RESULTS: CMRO2 did not differ between alpha-stat and pH-stat conditions (1.4 +/- 0.3 ml.100 g-1.min-1; median +/- quartile deviation), and was independent of order of determination. Changes in CBF between alpha-stat and pH-stat conditions were associated with proportional opposite changes in cerebral oxygen extraction. Cerebral blood flow was significantly greater with pH-stat management than with alpha-stat management (37 +/- 5 vs. 30 +/- 3 ml.100 g-1.min-1, respectively). The CBF response to changing PaCO2 was significantly greater when going from alpha-stat to pH-stat conditions (group 1) than in the reverse order (group 2). CONCLUSIONS: During cardiopulmonary bypass at 27 degrees C, hypothermic acid-base management has no measurable effect on CMRO2. CMRO2 was neither extraction limited nor dependent on either PaCO2, CBF, or hemoglobin oxygen affinity differences between alpha-stat and pH-stat management. Cerebral blood flow responses to changing CMRO2 depend on the "starting" conditions, with alpha-stat management appearing to better preserve CBF reactivity than pH-stat management.
Acid-Base Equilibrium↗
Characterization of a human cell line expressing high levels of cDNA-derived CYP2D6.
We have developed a human B-lymphoblastoid cell, designated h2D6v2, which expresses high levels of CYP2D6 cDNA. Microsomal P450 contents of 160 pmol mg-1 protein were observed. NADPH-fortified microsomes exhibited a substantial capacity to hydroxylate the prototype CYP2D6 substrates bufuralol and debrisoquine. Kinetic parameters, apparent Km, turnover number, Ki for quinidine inhibition and stereospecificity of bufuralol hydroxylation, observed with the human lymphoblast expressed enzyme were similar to those observed in human liver microsomes or purified liver CYP2D6 proteins. Therefore, the human lymphoblast expressed material appears to faithfully reflect the authentic protein. Relative to control cells, h2D6v2 cells were more sensitive to the cytotoxicity and mutagenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), supporting our previous observation with a cell line expressing lower levels of CYP2D6. h2D6v2 microsomes were capable of metabolizing NNK and NNK metabolism and mutagenicity were markedly inhibited by the addition of quinidine, a CYP2D6 inhibitor. h2D6v2 cells coupled with control cells, represent a useful in vitro system for studying xenobiotic metabolism by the clinically important, polymorphic CYP2D6. The human lymphoblast system offers the desirable ability to couple metabolic transformation studies with toxicological endpoints such as cytotoxicity and mutagenicity.
B-Lymphocytes↗
Reliability of an index of child characteristics.
The ABILITIES index provides a means to describe nine areas of functional abilities and disabilities. In this study, the authors examined the agreement between ratings made by 130 parents and teachers, 130 parents and specialists, and 125 teachers and specialists. Stability of ratings was assessed by asking 40 teachers to complete the index a second time, an average of 34 days after the first rating. The results suggest that raters who vary considerably in expertise, discipline and relationship to the child generally agree as to the child's presenting characteristics.
Adult↗
Hsp 47 is localized to regions of type I collagen production in developing murine femurs and molars.
To determine whether the proposed molecular chaperone Hsp47 is associated with the production of heterotrimeric procollagen, the distribution of anti-Hsp47 and anti-collagen antibodies were examined in developing murine femurs and molars of 22-23-day CD-1 mice. In addition, the expression of Hsp47, and collagen mRNAs were assessed by in situ hybridization using oligonucleotide probes. These studies revealed that Hsp47 was developmentally expressed and produced in regions that are coincident with type I collagen. Hsp47 was not localized in cartilaginous zones of developing femurs or in the regions of developing molars producing type III collagen. These results support the hypothesis that Hsp47 is necessary for the assurance of type I procollagen and is not expressed with other homotrimeric procollagen molecules.
Animals↗
Transluminal angioplasty for atherosclerotic disease of the vertebral and basilar arteries.
Transluminal angioplasty for hemodynamically significant stenosis (> 70%) involving the posterior cerebral circulation is now being performed by the authors in selected cases. A total of 42 lesions affecting the vertebral or basilar artery have been successfully treated by percutaneous transluminal angioplasty techniques in 41 patients. The lesions involved the proximal vertebral artery in 34 cases, the distal vertebral artery in five, and the basilar artery in three. Patients were examined clinically at 1 to 3 and 6 to 12 months after angioplasty. Three (7.1%) permanent complications occurred, consisting of stroke in two cases and vessel rupture in one. There were four (9.5%) transient complications (< 30 minutes): two cases of vessel spasm and two of cerebral ischemia. Clinical follow-up examination demonstrated improvement of symptoms in 39 cases (92.9%). Radiographic follow-up studies demonstrated three cases (7.1%) of restenosis involving the proximal vertebral artery; two were treated by repeat angioplasty without complication, and the third is being followed clinically while the patient remains asymptomatic. In patients with significant atherosclerotic stenosis involving the vertebral or basilar artery territories, transluminal angioplasty may be of significant benefit in alleviating symptoms and improving blood flow to the posterior cerebral circulation.
Adult↗