FK 506 has no short-term effects on endogenous or exogenous myeloid reconstitution in irradiated mice.
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Biomedical subjects
Publications and source records attributed to M Cooper.
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The effects of diazepam on regional cerebral metabolism were examined in eight healthy volunteers using positron emission tomography with 18-fluorodeoxyglucose as the tracer. Each subject was tested three times, at 1-week intervals, with placebo, a low oral dose of diazepam (0.07 mg/kg), and a moderate dose of diazepam (0.14 mg/kg). Subjects completed mood questionnaires before and at regular intervals after taking the drug, and performed a vigilance task during the 60-minute period of tracer uptake. The effects of the drug on cerebral metabolism were examined alone and in relation to the subjective and behavioral effects of the drug. Both doses of diazepam decreased global (whole brain) metabolic rate but did not affect specific regions differentially. Subjects experienced sedative like effects during all three scans (placebo as well as drug). Compared to placebo, both doses of diazepam decreased anxiety, and neither dose produced significant impairment of task performance. Neither the subjective nor behavioral drug effects were correlated with the changes in metabolic rate. Thus, diazepam decreased whole brain metabolic rate at doses that produced only modest subjective or behavioral effects. The changes in metabolic rate were not clearly related to other observable drug effects.
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Children between 9 and 12 months of age were studied to determine if they would spontaneously imitate either the average fundamental frequency or the fundamental frequency contour of their speaking partners. In the first experiment, children were recorded at home as they interacted with their fathers and mothers. Acoustic analyses failed to reveal any tendency on the part of the infants to adjust vocal pitch, amplitude, or duration to those of their speaking partners. In a second experiment, children were recorded while interacting with their parents in a laboratory setting. Again, there were no indications that the children imitated the vocal patterns of their speaking partners.
The space program is aiming towards the permanent use of space; to build and establish an orbital space station, a Moon base and depart to Mars and beyond. We must look after the total independency from the Earth's natural resources and work in the design of a modular space base in which each module is capable of duplicating one natural process, and that all these modules in combination take us to conceive a space base capable of sustaining life. Every area of human knowledge must be involved. This modular concept will let us see other space goals as extensions of the primary project. The basic technology has to be defined, then relatively minor adjustments will let us reach new objectives such as a first approach for a lunar base and for a Mars manned mission. This concept aims towards an open technology in which standards and recommendations will be created to assemble huge space bases and spaceships from specific modules that perform certain functions, that in combination will let us reach the status of permanent use and exploration of space.
Tissue culture cells were exposed to supernatants of Helicobacter pylori for 24 h at 37 degrees C in the presence of various quantities of urea. In the normal human stomach the concentration of urea is less than or equal to 4 mmol/l, and in the presence of this low concentration up to 10% of Vero cells showed intracellular vacuolization. In the presence of 7.5 mmol/l urea, 25% of the cells showed vacuolization. With 30 mmol/l urea, the final pH was 7.6, indicating that vacuolization was not due to change of pH. The first report of vacuolization of tissue culture cells by H. pylori was in a system without added urea but with concentrated bacterial supernatant; 30% of H. pylori strains demonstrated a cytotoxic effect. In those experiments fetal calf serum was used; it contains 6 mmol/l urea but was used at a concentration of 10%. A urease inhibitor, acetohydroxamic acid, caused a 75% drop in the number of cells showing vacuolization, and ammonia caused vacuolization. Thus the urea of H. pylori probably causes this vacuolization.
Some plate-grown strains of Helicobacter (Campylobacter) pylori that were harvested into phosphate-buffered saline and left for 1 h released soluble haemagglutinins. These caused high-titre agglutination of human and guinea-pig erythrocytes, whereas chicken, sheep and bovine erythrocytes were agglutinated at various titres. Six of 10 strains which had been subcultured repeatedly did not possess soluble haemagglutinins. Slide agglutination of bacterial suspensions demarcated the strains into two groups; Group 1 gave strong agglutination with most types of erythrocyte, Group 2 did not. By microtitration assay, all Group-1 strains but only two Group-2 strains produced a soluble haemagglutinin. Cell-associated haemagglutinins were found by microtitration assay in all strains of H. pylori, but higher titres were found within Group-1 strains. The supernates of broth-grown, shaken cultures also showed the presence of soluble haemagglutinins, with higher titres for recently isolated strains. Pre-treatment of human erythrocytes with neuraminidase from Arthrobacter ureafaciens and Clostridium perfringens abolished haemagglutination by the soluble, but not by the cell-associated haemagglutinin. The soluble haemagglutinin was inhibited by sialoproteins containing predominantly the N-acetylneuraminyl (2-3) galactopyranosyl [NeuAc(2-3)Gal] structure, fetuin, glycophorin and bovine N-acetylneuraminyl-lactose (NeuAc-Lac). Transferrin and human NeuAc-Lac, which contain predominantly the N-acetylneuraminyl (2-6) galactopyranosyl [NeuAc(2-6)Gal] structure were not inhibitory. However, bovine submaxillary mucin (BSM) was strongly inhibitory; it contains several structures with sialic acid linked 2-6 to oligosaccharides. These results suggest that the soluble haemagglutinin recognises a NeuAc(2-3)Gal structure, but has high affinity for another, as yet undetermined, sialic acid-containing structure.
This study examined the effects of ethanol on regional cerebral metabolic rate using positron emission tomography (PET). The study explored the relationship between the mood-altering effects of ethanol and its effects on regional cerebral glucose utilization (CMRglu) in eight healthy male volunteers. In the first phase of the study, the subjects participated in a behavioral preference procedure conducted in a recreational environment to determine their responses to ethanol (0.5 g/kg) in a naturalistic setting. They then participated in three PET sessions, receiving at three to seven day intervals, in counterbalanced order, placebo, 0.5 g/kg or 0.8 g/kg ethanol. PET scans were conducted using a PETT-VI scanner with F-18-2-fluoro-2-deoxyglucose (FDG) as the tracer. The mood-altering effects of ethanol were measured in both the naturalistic and the PET phases of the study. Ethanol produced comparable effects on mood in the naturalistic and the PET settings (i.e., increases in positive mood). The lower dose of ethanol produced variable effects on whole brain and regional CMRglu across subjects. There was some suggestion that certain regional metabolic changes after ethanol were correlated with subjective responses to the drug. The higher dose of ethanol decreased whole brain CMRglu in most subjects. All regions were affected about equally. It was concluded that the mood-altering effects of ethanol are not related in a simple manner to regional changes in CMRglu.
The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose.
A 52 year old man presented with myoglobinuria-induced acute renal failure requiring dialysis. Despite renal biopsy, the cause of the myoglobinuria was not established until he re-presented a year later with a milder episode. At this stage investigations, including a muscle biopsy, demonstrated a defect in fatty acid oxidation amenable to dietary and lifestyle advice. This report emphasizes the importance of reaching a definitive diagnosis in myoglobinuria.
We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM.(ABSTRACT TRUNCATED AT 250 WORDS)
Sera of cottontail rabbits (Sylvilagus floridanus) collected in southern Illinois in 1983 and 1984 were screened for the presence of antibodies against Francisella tularensis by rapid slide agglutination and enzyme linked immunosorbent assay techniques; 6% of 118 and 16% of 119 samples were positive by these methods, respectively. Rabbits gained, lost and maintained titers over at least an 8 mo period. Francisella tularensis tularensis was isolated from one serologically negative, clinically healthy rabbit.
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Lymphocytes leaving the thymus via two different pathways were examined as to their morphology and phenotype. Cells leaving the thymus via lymphatics were obtained by a direct cannulation of thymic lymphatics and those leaving via the thymic vein were labelled within the thymus using an extracorporeal perfusion system and identified subsequently as fluorescent cells in the draining vein. In both cases the cervical thymus in lambs was used, since it is located in the neck region and ensures easy access to both blood and lymphatic vessels of the thymus without subjecting the animal to a major trauma or stress. Cells obtained from the thymic lymphatics or lymphatic emigrants were found to have distinct features different from peripheral T cells in terms of their surface morphology and expression of the MHC antigens. Venous emigrants were also slightly different from peripheral T cells in MHC expression. Estimation on the rate of thymocyte emigration into the periphery suggested that neither venous nor lymphatic emigrants represent a major fraction of de novo synthesized cells in the thymus of this animal species, as has been suggested in the mouse.
Abetalipoproteinemia (ABLP) is a rare autosomal recessive disease characterized by a lack of plasma apolipoprotein B (apo B). In this report, the hypothesis that ABLP is due to rare mutations in the apo B gene was tested. A total of eight ABLP families were studied. Apo B gene RFLPs were used to establish the haplotypes of the apo B alleles in family members. LOD score analysis was used to study the linkage between the apo B alleles and ABLP. These families were categorized arbitrarily as class I, II, III, or IV because of differences in the results derived from both haplotyping and LOD score analysis. In a class I family, affected siblings, who on the basis of the hypothesis would be expected to have the same apo B alleles, had different ones. LOD score analysis of this family gave an infinite negative number at a recombination fraction (theta) of zero. In two class II families, probands who were the result of consanguineous marriages and who, on the basis of the hypothesis, should be homozygotes for a defective apo B allele, were heterozygotes at this locus. The sum of the LOD scores from these two families was -1.7 at theta = 0. In one class III family, a parent was apparently homozygous for a particular apo B allele and yet not affected. This also contributed negatively to the LOD score. In four class IV families, disease inheritance was compatible with segregation of the apo B alleles. This, however, was not statistically significant (LOD score = 0.97 at theta = 0).(ABSTRACT TRUNCATED AT 250 WORDS)
We have evaluated the relationship between the neuronal myc gene (NMYC) and class I major histocompatibility complex (MHC) expression in human neuroblastoma (NB) tumor cell lines. Class I MHC surface Ag expression in NB cell lines varied from nearly undetectable to levels nearly as high as in a lymphoblastoid cell line. Class I MHC mRNA levels in NMYC-amplified NB cell lines were lower than levels observed in single copy NMYC NB cell lines. However, considerable variation in class I MHC surface Ag and mRNA expression was evident in NMYC-amplified cell lines. To determine directly whether NMYC might modulate class I MHC expression in NB, we transfected a plasmid containing a recombinant NMYC gene into two tumor cell lines derived from a NB and a related neuroepithelioma tumor. Constitutive overexpression of the recombinant NMYC gene produced no consistent change in class I MHC surface Ag or mRNA levels. To determine whether class I MHC expression might be developmentally regulated in adrenal medullary cells, the precursor cells of adrenal NB tumors, beta 2-microglobulin expression was measured in fetal and adult adrenal glands. beta 2-Microglobulin expression was not evident in the neuroblasts of a 24-wk-old fetal adrenal gland, whereas beta 2-microglobulin expression was present in the adult adrenal medulla. These data suggest that variation in class I MHC expression among NB cells may reflect the developmental stage at which neuroblasts were arrested during tumorigenesis.