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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 433 records · Page 24Linked to original sources

Biochemical purification and partial characterization of a murine macrophage surface receptor possessing specificity for small aromatic moieties including fluorescein.

Binding properties and requirements for internalization of hapten-protein antigens, such as fluorescein-polyderivatized bovine serum albumin (FITC-BSA) and poly-D-lysine (FITC-PDL), by murine macrophage was consistent with surface receptor recognition of fluorescyl moieties (Cherukuri et al., Mol. Immunol. 34, 21-32, 1997; Cherukuri et al., Cytometry 31, 110-124, 1998). Ligand binding properties of the putative macrophage receptor pointed toward specificity for various aromatic moieties including phenylalanine, phenyloxazolone and fluorescein (Cherukuri and Voss, Mol. Immunol. 35, 115-125, 1998). Purification of the hapten-recognizing receptor from J774 macrophage cells involved subcellular fractionation of plasma membrane fractions, and affinity chromatography of solubilized membranes employing a phenyl-Sepharose adsorbent with subsequent specific elution of receptor using fluorescein ligand. The final product was a protein with a molecular mass of approximately 180 kDa. Characterization of the purified receptor involved absorption and fluorescence spectroscopy, circular dichroism, fluorescence quenching analyses, various ligand binding assays and an immunological analysis. Spectroscopic analyses revealed that the receptor possessed aromatic amino acids while circular dichroism suggested significant alpha-helical secondary structure. Binding specificity of the purified receptor was confirmed in a spectrofluorometric assay where the fluorescence of fluorescein ligand was quenched approximately 97%. Finally, specific binding activity of the receptor with FITC-BSA was demonstrated in Western blot analysis under native conditions. Receptor purity was confirmed in amino acid sequencing analysis when the amino-terminal residue was found to be totally blocked. Results are discussed in terms of the possible identity of the isolated macrophage receptor and its biological-immunological role.

Animals↗

Maternal perception of preterm labor: is it reliable?

The objective of this study was to determine the reliability of maternal perception of uterine contractions and the influence of gestational age and maternal training on the perception level. Three hundred fifty patients at high risk for preterm delivery were followed from 20 to 35 weeks of gestation. The average maternal perception (79%) of contractions did not significantly vary as a function of gestational age. Four groups of women were identified according to the perception index (PI) defined as the ratio of contractions felt by the mother and the contractions documented by tocodynamometer. Within each group, the PI did not significantly vary during consecutive monitoring sessions, as the women become more familiar with self detection of uterine contractions (R < .65, P > .95). Twenty-one percent (+/-5%) of all preterm uterine contractions were not perceived by the pregnant women from 21 to 35 weeks. Thirty-two patients (9.1%) fail to perceive most or all uterine contractions while 189 (54%) detect most or all at any time during the study period.

Female↗

Hepatitis B virus DNA in the sera of HBsAg carriers: a marker of active hepatitis B virus replication in the liver.

Sera and liver biopsies from 30 Italian patients, carriers of HBsAg for at least 3 years, were examined for markers of hepatitis B virus (HBV) infection by serological assays and immunofluorescence. Biopsies were analyzed for HBcAg, HBsAg, and delta antigen by immunofluorescence; sera were assayed for HBsAg/anti-HBs, HBcAg/anti-HBc, HBeAg/anti-HBe, delta/anti-delta, HBV-specific DNA polymerase activity and the presence of HBV DNA. HBcAg, HBeAg, and DNA polymerase tests were positive in the sera of 71, 86, and 57%, respectively, of carriers with intrahepatic HBcAg. HBV DNA was detected in 100% of patients expressing HBcAg in the liver with a strong correlation between the concentration of serum DNA and the intensity of HBcAg immunofluorescence in the liver. HBV DNA was detected in the sera of 63% of carriers with intrahepatic delta where the other markers of HBV replication (HBeAg, DNA polymerase) were undetectable. The assay for serum HBV DNA appears to be an excellent noninvasive method for detecting active replication of HBV in HBsAg carriers.

Carrier State↗

Transmission of ground squirrel hepatitis virus to homologous and heterologous hosts.

The infectivity and host range of ground squirrel hepatitis virus (GSHV) have been further examined by animal inoculation experiments. Although carrier squirrel sera usually harbor 10(9) to 10(10) virions per ml as determined by physical measurements, titration of one such serum revealed that squirrel infectivity was lost following dilution of the sample over 10(6)-fold. Infectivity is markedly reduced by NP40 pretreatment of infected serum. GSHV infection cannot be readily transmitted to several related ground squirrel species, but chipmunks can be experimentally infected by GSHV virions or by cloned GSHV DNA, and the resulting infection closely resembles that seen in the normal host.

Animals↗

Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder.

Depressed patients have been reported to have a higher than normal density of platelet binding sites for 3H-clonidine, an alpha 2-adrenoceptor agonist. Paradoxically, other studies using 3H-alpha 2, antagonists have found no differences from controls. Because 3H-clonidine interacts with platelet alpha 2-adrenoceptors to form G-protein complexes, whereas 3H-alpha 2-antagonists bind with uncoupled receptors, an elevation in G-protein coupling might explain this paradox. Another possibility is that depression might be associated with increased non-adrenergic I1-imidazoline binding sites, which are also clonidine sensitive. To distinguish these possibilities, we utilized p125I-clonidine to measure density (Bmax) and affinity (KD) of platelet G-protein coupled alpha 2-adrenoceptors as well as platelet I1 binding sites, and compared diagnostic groups of major depressive disorder (MDD), generalized anxiety disorder (GAD) and healthy subjects. Specific inhibition of binding by norepinephrine (NE = 10 microM) was used to selectively quantify alpha 2-adrenoceptors, whereas inhibition by 10 microM moxonidine (a > 100-fold selective I1 ligand) quantified I1 binding sites under a NE mask. I1 sites were found to be markedly elevated by, on average, +136% in MDD patients (p = .0007), whereas there was only a marginal increase in alpha 2-adrenoceptor Bmax values in MDD patients (p = .08; GAD and healthy subjects did not differ). Treatment of MDD patients for 6-8 weeks with desipramine downregulated I1 sites as well as alpha 2-adrenoceptors. Positive correlations were also noted for both sites: (a) between Bmax values and the severity of depression (using the Hamilton Depression Rating Scale); and (b) between end-of-treatment plasma desipramine concentrations and the extent of downregulation in Bmax values when subject groups were pooled. None of the binding parameters was associated with plasma catecholamine concentrations. The results suggest that an increased density of platelet I1 binding sites may partially explain the utility of radiolabeled clonidine as a potential biological marker for depressive illness, although an additional increase in G-protein coupling cannot be excluded.

Adult↗

Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study.

Midlife hypertension is associated with later development of cognitive impairment, vascular dementia (VsD), and possibly Alzheimer's disease (AD). Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure (BP), however, to our knowledge there have been no prospective investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD. We investigated the relationship of BP level in midlife to development of neurofibrillary tangles (NFT), neuritic plaques (NP), and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study (HHP/HAAS) cohort. The HHP/HAAS is a population-based, longitudinal study of cognitive function and dementia with 36 years of follow-up. Neocortical and hippocampal NFT and NP were counted per mm(2), and fixed brain weight was measured for 243 decedents. Elevated systolic BP, (> or =160 mm Hg) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus. Diastolic BP elevation, (> or =95 mm Hg) was associated with greater numbers of NFT in hippocampus. Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions, there is a direct relationship with brain atrophy, NP and NFT.

Aged↗

Primary structure of human T-cell receptor alpha-chain.

The T-cell receptor has been studied intensely over the past 10 years in an effort to understand the molecular basis for major histocompatibility complex (MHC) restricted antigen recognition. The use of anti-receptor monoclonal antibodies to isolate and characterize the receptor from human and murine T-cell clones has shown that the protein consists of two disulphide-linked glycopeptides, alpha and beta, distinct from known immunoglobulin light and heavy chains. Like immunoglobulin light and heavy chains, however, both the alpha- and beta-chains are composed of variable and constant regions. Molecular cloning has revealed that the beta-chain is evolutionarily related to immunoglobulins, and is encoded in separate V (variable), D (diversity), J (joining) and C (constant) segments that are rearranged in T cells to produce a functional gene. We report here cDNA clones encoding the alpha-chain of the receptor of the human T-cell leukaemia line HPB-MLT. Using these cDNA probes, we find that expression of alpha-chain mRNA and rearrangement of an alpha-chain V-gene segment occur only in T cells. The protein sequence predicted by these cDNAs is homologous to T-cell receptor beta-chains and to immunoglobulin heavy and light chains, particularly in the V and J segments.

Amino Acid Sequence↗

Mutagenicity of N-nitroso derivatives of carbofuran and its toxic metabolites.

Carbofuran (CF), an insecticide and nematocide, is metabolically oxidized to two less toxic forms, 3-hydroxycarbofuran and 3-ketocarbofuran. The N-nitroso derivatives of carbofuran and its metabolites were synthesized by reaction with nitrite under acidic conditions. Products of the reaction were obtained by extraction, identified by thin-layer chromatography, and purified by silica gel column chromatography. All three nitroso derivatives reacted positively with Gries reagent and gave characteristic triplet absorption spectra (387, 402, and 422 nm). Structural confirmation was by nuclear magnetic resonance and mass spectroscopy. Mutagenicity was determined by the Ames assay method with Salmonella typhimurium strains TA98 and TA100. The nitroso derivatives of all three compounds responded similarly, given a mutation ratio of 45 at 5 micrograms per plate on TA100. In addition, all three produced chromosome aberrations in Chinese hamster ovary (CHO) cells. Only two of the three (nitrosocarbofuran and 3-hydroxynitrosocarbofuran) were also capable of inducing large numbers of sister chromatid exchanges in the same cells. Observed variations in maximum mutagenicity in the Ames test and the ability to induce sister chromatid exchanges in CHO cells are consistent with the stability of the compounds in aqueous solution.

Animals↗

Urinary excretion of cocaine, benzoylecgonine, and ecgonine methyl ester in humans.

The excretion kinetics of cocaine (C) and its two major metabolites, benzoylecgonine (BZ) and ecgonine methyl ester (EME), were determined by collecting all urine for 30 h from 5 cocaine users (subjects C, D, E, F, and G) given bolus doses followed by exponential cocaine infusions that delivered doses of 253 (subject C), 444 (subjects D, E, and F), and 700 mg (subject G). Plasma cocaine, urine cocaine, BZ, and EME were measured by gas chromatography, with a nitrogen detector. Elimination half-times for EME and BZ, estimated from semilog plots of excretion rates vs. time, averaged 3.1 and 4.5 h respectively, in agreement with our previous report. Urinary recovery in D, E, and F was 27-41% of the dose, with 14-17% as BZ, 12-21% as EME, and 2% as cocaine. Subject C excreted very little EME--5-6-fold less than the mean for the other subjects and amounting to only 3% of the dose. Cocaine disposition in subject G, who received the largest dose and attained plasma levels of 3000 ng/mL, showed some characteristics of a nonlinear process.

Adult↗

Ticlopidine-associated thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is a rare complication of ticlopidine treatment. This syndrome has been reported to occur typically within the first few weeks after the initiation of therapy. The authors describe a case of a 72-year-old woman in whom thrombotic thrombocytopenic purpura developed just 2 days after starting ticlopidine therapy for a new-onset ischemic stroke. The patient responded successfully to plasmapheresis. The authors are reporting this case to emphasize the unpredictable nature of the association between the drug and the disease, which necessitates careful hematologic monitoring.

Aged↗

The effect of pregnancy on mineralo- and gluco-corticoid secretion in the sheep.

1. The peripheral blood concentrations of aldosterone, corticosterone and cortisol were measured during pregnancy in conscious, undisturbed sheep. 2. Aldosterone levels did not change during pregnancy and the mean pregnant value, 1-2 s.d. 1-4 ng/100 ml(n = 12) was not significantly different from the non-pregnant value, 2-1 s.d. 1-7 (n = 16). 3. Cortisol levels likewise were unchanged by pregnancy-non-pregnant values were 0-56 s.d. 0-50 mug/100 ml (n = 12) compared with 0-46 s.d. 0-40 mug/100 ml (n = 16) in pregnant sheep. 4. Sheep of 110-140 days gestation had a 400 mmol greater total exchangeable sodium than non-pregnant sheep. Plasma volume and plasma renin concentration tended to be elevated near to term. 5. Very high aldosterone secretion rates and peripheral blood levels could be produced in pregnant sheep by stress, intravenous ACTH or angiotensin II infusions, and by sodium deficiency. It is suggested that the pregnant sheep may show increased sensitivity in contrast to non-pregnant sheep to these stimuli and the enlarged size of their adrenals may be a contributing factor.

Adrenocorticotropic Hormone↗

Exposure of rhesus monkeys to 20 000 G steady magnetic field: effect on blood parameters.

Sixteen monkeys were used in a study to determine the effects, or noneffects, of exposure to a steady magnetic field of 2 T (20 000 G). Arterial and venous blood samples were taken before, immediately after, and several weeks following the test. Blood gas analyses were made of arterial samples, and hemotologic cell data and Technicon SMAC analyses were made of venous samples. Differential and absolute white blood cell counts of segmented neutrophils and lymphocytes were considerably changed during the test, even for monkeys which were not exposed to the magnetic field. These changes have also been observed in monkeys whose environment and daily routine are modified appreciably. Eight of the 16 monkeys were tested twice: first, in the magnet with the magnet turned on, and second, two months later, in the magnet, but with the magnet turned off. A large superconducting magnet (0.63 m i. d. and 1.85 m long warm-air bore) was used, which accommodated two monkeys at one time. Paired-t tests of 45 blood parameters showed no significant differences between the two tests. Exposure to a gradient field compared with exposure to a uniform magnetic field showed no significant differences.

Animals↗

Neurobrucellosis--a rare complication of renal transplantation.

Brucellosis is an intracellular bacterial infection contracted by consuming raw milk or by contact with infected cattle. Neurobrucellosis is a rather rare manifestation of brucellosis and has protean clinical presentations characterized by meningoencephalitis, myelitis, myelopathies, subarachnoid hemorrhage and psychiatric manifestations. A depressed immune status is believed to be a risk factor for developing neurobrucellosis. We report a case of neurobrucellosis in a patient 13 years after a cadaveric renal transplantation. Even though a Brucella organism was not isolated from body fluids she satisfied other criteria for establishing the diagnosis. Treatment with doxycycline and rifampin led to a clinical cure as well as to marked improvement in the Brucella titer.

Brucellosis↗