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Biomedical subjects

A Ho

Publications and source records attributed to A Ho.

At least 127 records · Page 7Linked to original sources

Dopamine antagonist and "binge' cocaine effects on rat opioid and dopamine transporter mRNAs.

The modulation by selective dopamine receptor antagonists of the effects of "binge' cocaine (3 x 15 mg kg-1 day-1, i.p., for 3 days after 11 days of adaptation to saline injections) on preproenkephalin, preprodynorphin, kappa opioid receptor and dopamine transporter mRNAs was determined. Administration of cocaine was preceded by daily single injections of a D1 (SCH 23390; 2 mg kg-1) or the D2 (sulpiride; 50 mg kg-1) dopamine receptor antagonist. The D1, and not the D2, antagonist blocked cocaine-induced preprodynorphine and preproenkephalin increases in the caudate-putamen. Sulpiride alone, and sulpiride plus cocaine, increased preproenkephalin mRNA. Dopamine transporter mRNA levels showed a cocaine treatment-antagonist interaction. These data indicate that this administration paradigm elevates both preprodynorphin and preproenkephalin mRNAs by a D1-dependent mechanism not requiring D2 activation.

Analysis of Variance↗

Collagen-induced arthritis in CD4- or CD8-deficient mice: CD8+ T cells play a role in initiation and regulate recovery phase of collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an experimental autoimmune disease induced by immunization with collagen type II (CII). We studied CIA in CD4- or CD8-deficient DBA/1 mice to further define the roles of CD4+ and CD8+ T cells in the disease. CD4-deficient mice developed severe arthritis, and no differences in incidence, clinical course, and severity were observed between CD4 -/- and CD4 +/- mice. Proliferative responses of lymph node T cells to CII was, however, reduced in CD4 -/- mice, and inflamed joints revealed relative accumulation of CD4-CD8-TCR(alpha)(beta)+ cells. A CII-specific T cell line generated from CD4-deficient mice responded to CII in a MHC-restricted fashion and had a CD4-CD8-TCR(alpha)(beta)+ phenotype. Disease incidence in CD8 -/- mice was significantly decreased compared with CD8 +/- mice, even though the severity of arthritis in arthritic mice was not different. These results suggests a role for CD8+ T cells in initiating CIA. Interestingly, CD8-deficient mice were more susceptible to a second induction of arthritis after remission of initial disease, pointing towards an immunoregulatory role for CD8+ T cells. CD8-deficient mice did not, however, show any defect in oral tolerance induction using CII. Taken together, our findings demonstrate that CD4-CD8-TCR(alpha)(beta) cells can trigger systemic arthritis in CD4-deficient mice and that CD8+ T cells can play dual and opposing roles, important both in initiation of CIA and in providing resistance to reinduction of CIA after recovery from initial disease.

Animals↗

Regulation of kappa opioid receptor mRNA in the rat brain by "binge' pattern cocaine administration and correlation with preprodynorphin mRNA.

We previously reported that 'binge' pattern administration of cocaine elevates preprodynorphin (ppDyn) mRNA in the caudate-putamen of rats. The present study confirms this finding. In addition, we report here that "binge' pattern administration of cocaine leads to a significant decrease in the mean level of kappa opioid receptor (KOR) mRNA in the substantia nigra, with no significant change in the mean level of KOR mRNA in the caudate-putamen. The decrease in KOR mRNA in the substantia nigra after 3 day or 14 day 'binge' administration of cocaine was comparable to the increase in ppDyn mRNA in the caudate-putamen. While there was no significant change in the mean levels of KOR mRNA in the caudate-putamen following cocaine administration, there was a positive within animal correlation between the levels of ppDyn mRNA and KOR mRNA in the caudate-putamen, both in animals administered saline and in animals receiving 'binge' cocaine for 14 days. Finally, mean levels of ppDyn or KOR mRNA in cocaine treated rats were not different from saline treated controls following a 10 day withdrawal from 14 days of 'binge' cocaine administration. The results provide evidence of regulation of KOR mRNA by cocaine in the substantia nigra.

Animals↗

Modulation of CRF-R1 mRNA in rat anterior pituitary by dexamethasone: correlation with POMC mRNA.

Glucocorticoids have been shown to decrease CRF receptor binding in the anterior pituitary. To determine whether glucocorticoids or CRF peptide modulate CRF-R1 gene expression, CRF-R1 mRNA levels in rat pituitary and brain were measured after administration of a synthetic glucocorticoid, dexamethasone (DEX) or rat/human CRF (r/hCRF), using a sensitive solution hybridization RNase protection assay. DEX (400 micrograms/day) or r/hCRF (100 micrograms/kg/day) was administered twice daily for 5 days to male rats. DEX treatment caused a significant decrease in CRF-R1 mRNA levels in the anterior pituitary. Also, a significant positive correlation was found between CRF-R1 and POMC mRNA levels in the anterior pituitary of the individual animals: levels of both mRNAs were reduced by DEX. However, r/hCRF treatment had no significant effect on CRF-R1 mRNA levels in the anterior pituitary. In extrahypothalamic brain regions, mRNA levels of CRF-R1 did not change following either DEX or r/hCRF administration. Our data suggest that in addition to POMC and CRF genes, CRF-R1 gene may also be subject to negative feedback control by glucocorticoids.

Amygdala↗

Quantitation of incident spinal fractures: comparison of visual detection with quantitative morphometry.

The value of quantitative morphometry in detection of new spinal fractures was assessed in serial radiographs from 83 patients with osteoporosis. From vertebral landmarks on lateral spine radiographs, a computer program allowed calculation of vertebral heights and area. By comparing vertebral dimensions in the two sets of films, incident spinal fractures could be quantitated based either on the minimum criteria of 15% reduction in vertebral height (CM2) or a fall in height and area of 20% and 10% (CM1). The results of quantitative morphometry were compared with those of the consensus and individual readings of visual detection by three experienced investigators in the same paired sets of spinal films. For incident new fractures, the visual consensus method (V-C) showed a very good agreement with individual visual detection (kappa of 0.794 to 0.916) as well as with CM1 (kappa of 0.821). However, there was a poor agreement between the results of consensus reading and of detection by CM2 (kappa of 0.341), due to excessive number of fractures identified by CM2, but not by the visual method. For incident recurrent fractures, there was a poor agreement between V-C and individual visual detection, and between V-C and quantitative morphometry (kappa of 0.306 to 0.496). It was due to severe compression fractures at baseline, which caused further changes in vertebral dimensions difficult to measure accurately by either visual or quantitative morphometry. Thus, if the visual detection of fractures by a consensus of experienced investigators is considered as the "gold standard," quantitative morphometry, based on minimum reduction in vertebral height of 20% accompanied by a minimum decline in area of 10%, provides an objective detection of incident new spinal fractures but not of recurrent fractures.

Aged↗

Urinary tract infection caused by Mycobacterium terrae complex.

We describe a case of recurrent urinary tract infection caused by Mycobacterium terrae complex in a patient with obstructive nephropathy. The mycobacterium was resistant to most antituberculosis drugs and despite its apparent clearance in the urine, the patient finally died of urinary sepsis caused by multiple bacterial pathogens.

Aged↗

Sources of error for periodontal probing measurements.

This study determined the relative contribution to probing measurement reliability of several factors, compared with that of random error. Probing measurements were performed by examiners properly trained and calibrated. A total of 5771 pairs of replicate pocket depth (PD) and relative attachment level (RAL) measurements were performed with the Florida Probe. A total of 1488 replicate clinical attachment level (CAL) measurements were performed with the North Carolina 15 mm probe. In addition, longitudinal replicate measurements of RAL were performed at 0 and 12 months on 816 sites in 11 patients utilizing the Florida Probe 20 mm disk probe. Measurement reliability with the Florida Probe resulted in mean intraexaminer variances of 0.21 and 0.33, for PD and RAL, respectively (s.e.m. 0.46 mm for PD and 0.57 mm for RAL). Measurement reliability with the conventional probe resulted in mean intra-examiner variances of 0.19 for PD and 0.32 for CAL (s.e.m. 0.44 mm and 0.56 mm). Pocket depth contributed to = 5% of the variability of the intra-examiner variance with both probes with other contributing factors being the individual patient, tooth and site location. Mean intra-examiner reproducibility for duplicate RAL measurement performed at 0 and 12 months was 0.24 and 0.19, respectively (s.e.m. 0.49 mm and 0.43 mm). In conclusion, a mean intra-examiner variance of < or = 0.24 can be achieved for replicate measurements with both electronic and conventional probes for moderate and severe periodontitis patients. Individual examiner, individual patient and site location contribute up to 10% to the overall variance. Hence, the pattern of variability for intra-examiner variance of probing measurements performed with either electronic or conventional probes by trained and calibrated examiners is mostly random error.

Adult↗

Occupational asthma due to latex in health care workers.

Immediate hypersensitivity reactions ranging from mild urticaria to life threatening anaphylaxis after exposure to natural rubber latex have been reported frequently in health care workers while occupational asthma due to latex exposure is less well studied. The results of specific challenge tests and immunological tests in four health care workers with work related respiratory and skin disorders induced by the use of latex gloves are described. Occupational asthma was confirmed in three subjects by specific challenge tests. All had a positive skin test reaction to the latex extract; specific IgE antibodies were detected in only one subject. The fourth subject had a negative specific inhalation and skin test reaction to the latex extract. Peak expiratory flow monitoring at work and away from work showed a pattern consistent with work related asthma. These findings confirm that latex is a cause of occupational asthma in health care workers.

Adult↗

Both dynorphin A(1-17) and [Des-Tyr1]dynorphin A(2-17) inhibit adenylyl cyclase activity in rat caudate putamen.

In this study, the ability of a series of dynorphin peptides to inhibit adenylyl cyclase (AC) activity was determined. The endogenous ligand of the kappa opioid receptor, dynorphin A(l-17) (Dyn A(l-17)), produced a significant concentration-dependent inhibition of AC activity in membranes prepared from the caudate putamen (CPu) of naive Fischer 344 rats. The opioid receptor antagonist, naloxone (10(-5)M), which is predominantly mu opioid receptor directed, but with modest kappa and delta receptor activity, partially blocked this inhibition. Nor-Binaltorphimine (10(-5)M), the selective kappa receptor antagonist, also blocked the effect of Dyn A(l-17), but to a lesser degree. [Des-Tyr1]Dyn A(2-17), a major nonopioid biotransformation product of Dyn A(l-17) with known biological activities, also inhibited AC in rat CPu membranes. Dyn A(l-13) inhibited AC, as did its major opioid biotransformation product, Dyn A(l-12). One of the major nonopioid biotransformation products of Dyn A(l-13), Dyn A(4-12), showed no activity. Dyn A(2-12), another nonopioid product of Dyn A(l-13), showed limited activity. Dyn A(l-6), a minor biotransformation product of both Dyn A(l-17) and Dyn A(l-13), also inhibited AC activity. These findings suggest that, in rat CPu membranes, the inhibition of AC activity by Dyn A(l-17) is mediated in part by kappa and mu opioid receptors. In addition, Dyn A(2-17), and to a lesser extent Dyn A(2-12), may bind to a yet unidentified site that is also coupled to the AC enzyme in rat CPU.

Adenylyl Cyclase Inhibitors↗

Corticotropin-releasing factor and type 1 corticotropin-releasing factor receptor messenger RNAs in rat brain and pituitary during "binge"-pattern cocaine administration and chronic withdrawal.

Endogenous central corticotropin-releasing factor (CRF) may be involved in the neuroendocrine and behavioral responses to cocaine. In the present study, levels of CRF mRNA were measured in the hypothalamus and in several extrahypothalamic brain regions after different regimens of "binge"-pattern cocaine administration. Male Fischer rats were injected with saline or cocaine (15 mg/kg, 1 hr x 3/day) at the beginning of the light cycle, to approximate the manner in which cocaine is often abused by humans, both in terms of temporal pattern and in relation to circadian rhythm. Cocaine administered in this binge regimen produced time-dependent alterations of CRF mRNA levels in the hypothalamus. There was a significant increase in CRF mRNA levels on day 1, which returned to base-line levels on day 2, with elevated plasma corticosterone levels on both days. CRF receptor type 1 and prooplomeianocortin mRNA levels in the anterior lobe of the pituitary were not significantly altered after acute cocaine injections on day 1 or day 2. On day 14 of chronic binge-pattern cocaine administration, decreased hypothalamic CRF mRNA levels and an attenuated elevation in plasma corticosterone levels were found. After 10 days of withdrawal from 14-day binge cocaine, CRF mRNA returned to basal levels. CRF mRNA levels in the amygdala were also significantly increased on day 1 and returned to basal values on day 2. Chronic (14-day) binge cocaine administration did not alter CRF mRNA levels in the amygdala. These results suggest that the attenuated response in the hypothalamic-pituitary-adrenal axis to chronic binge cocaine administration is coupled to the cocaine-induced decreases in CRF gene expression in the hypothalamus and that activation of CRF gene expression in extrahypothalamic regions may have implications for a molecular understanding of the behavioral responses to cocaine.

Adrenocorticotropic Hormone↗

Simplified quantitation of urinary benzoylecgonine in cocaine addiction research and for related pharmacotherapeutic trials.

In clinical trials of potential pharmacotherapies for cocaine addiction, objective determination of subject relapse relies on qualitative urine analysis for benzoylecgonine, the major metabolite of cocaine. Unlike qualitative analysis, quantitative measurement allows differentiation between continued cocaine use and a single use, as well as identification of changes in the quantity of cocaine used at different times. The only quantitative technique that has been used is expensive and not generally feasible. This study was performed to modify an existing qualitative technique for use as a new simple and readily available quantitative method for identifying cocaine use among research subjects. Benzoylecgonine levels in 24-hour urine specimens collected from 11 cocaine-addicted subjects hospitalized in a research setting were measured semi-quantitatively by fluorescence polarization immunoassay. Accurate results required thorough mixing of urine specimens prior to analysis. At admission, eight subjects had urinary benzoylecgonine levels > or = 0.30 microgram/ml, the standard positive/negative cut-off used in qualitative analysis. The mean half-life of benzoylecgonine during initial elimination was 0.46 +/- 0.08 (SEM, n = 8) days. Benzoylecgonine (BE)/creatinine (C) levels remained > or = 0.30 microgramBE/mgC for 4.8 +/- 0.5 (n = 8) days and > or = 0.03 microgramBE/mgC for 10.5 +/- 1.5 (n = 8) days. Relapses in three subjects could be identified by quantitative analysis. This study indicates that quantitation of benzoylecgonine in daily urine specimens provides a sensitive, objective index to cocaine use.

Adolescent↗

Glutamate regulation of GDNF gene expression in the striatum and primary striatal astrocytes.

The aim of this study was to investigate the regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA by activation of glutamate receptors in the rat striatum. We observed an increase in GDNF mRNA levels in the adult rat striatum after administration of subseizure doses of N-methyl-D,L-aspartic acid (NMA) and kainic acid. Since it is unclear whether the upregulation of GDNF occurred in neurons or astrocytes within the striatum, we further investigated whether GDNF gene expression in primary striatal astrocytes in culture could be regulated by glutamate receptor activation. We found that treatment of the cultures with NMA and kainic acid similarly upregulated GDNF gene expression as observed in vivo, suggesting that striatal astrocytes express functional glutamate receptors. Immunocytochemical and nuclease protection analysis revealed that striatal astrocytes expressed the NMDA-R1 subunit. These findings suggest the regulation of GDNF mRNA in the striatum may be mediated by excitation of glutamate receptors via glutamatergic cortical afferents.

Animals↗

Major histocompatibility proteins, anti-Hu antibodies, and paraneoplastic encephalomyelitis in neuroblastoma and small cell lung cancer.

BACKGROUND: Patients with neuroendocrine-related tumors and paraneoplastic encephalomyelitis (PEM) or paraneoplastic sensory neuronopathy (PSN) develop high titers of antibodies, called anti-Hu, against neuronal proteins expressed in their tumors, usually small cell lung cancer (SCLC). These tumors appear to be more indolent than those not associated with anti-Hu antibodies. The aims of this study were to determine 1) if patients with neuroblastoma (NB) also have anti-Hu antibodies, 2) the correlation between antibody titer and survival, and 3) if coexpression of Hu antigens and major histocompatibility proteins (MHC) by the tumor correlates with the development of anti-Hu associated PEM/PSN: METHODS: Using immunohistochemistry and Western blot analysis, the sera of 109 patients with NB whose neurologic condition was concealed at the time of the study were examined for the presence of anti-Hu antibodies. The expression of Hu antigens and MHC proteins in 50 nonselected NB and 26 SCLC (16 known to be from seropositive and 10 from seronegative patients) was examined using immunohistochemistry. RESULTS: Four Stage 4 NB patients were seropositive and had longer survival (median 86 months) than 71 seronegative patients in the same age group and with the same tumor stage (median survival, 28.5 months). Seventy-eight percent of NB and all SCLC expressed Hu antigens. Overall, 17 of 20 tumors from seropositive patients expressed both Hu and MHC Class I proteins, but only 4 of 30 tumors from seronegative patients expressed both proteins (P < 0.0001). CONCLUSIONS: 1) Some patients with NB develop anti-Hu antibodies; a search for that type of tumor is indicated in seropositive children, 2) most NBs and SCLCs express Hu antigens but only a few are associated with anti-Hu antibodies, and 3) Class I MHC expressed by some Hu antigen-bearing tumors may play a role in the development of anti-Hu associated PEM/PSN:

Adult↗

Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells.

MRL/lpr mice develop a systemic autoimmune disease similar to systemic lupus erythematosus in humans. The mice show progressive lymphadenopathy due to the accumulation of an unusual population of CD4-8-(DN) B220+ alpha beta+ T cells. We bred MRL/lpr mice with mice lacking CD4+ or CD8+ T cells by gene targeting via homologous recombination in embryonal stem cells to determine the roles of these cells in the autoimmune disease. No difference in survival or autoantibody levels was noted between CD8-/-lpr and littermate controls. Interestingly, these CD8-/- lpr mice have a reduced level of B220+ DN T cells despite the fact that the degree of lymphadenopathy was unaltered. CD4-/- lpr mice had a diminished autoimmune disease with a reduction in autoantibody production and skin vasculitits, and increased survival compared to littermate controls. However, CD4-/- lpr mice had an enhanced splenomegaly that developed massively by 16-20 weeks of age (5 to 8 greater than lpr control mice) due to the accumulation of DN B220+ T cells. In addition, there were no differences in peripheral lymph node enlargement, although the proportion of DN B220+ T cells was about twofold higher in the CD4-/- lpr mice. These cells were phenotypically identical to the DN population in control lpr mice, indicating that the accumulating DN T cells can be dissociated from the autoimmune disease in these mice. Collectively, our results reveal that the autoimmune disease is dependent on CD4+, but not CD8+ T cells, and that many of the B220+ DN T cells traverse a CD8 developmental pathway.

Animals↗

Invasive Haemophilus influenzae type b infections in children hospitalized in Hong Kong, 1986-1990. Hong Kong Hib Study Group.

A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b diseases was conducted in Hong Kong. Between 1986 and 1990, 57 cases (28 male) were recorded in children less than 12 years old (37 cases of meningitis, 9 of septicaemia and 11 of bacteraemic pneumonia). The annual incidence for children less than 5 years old was 2.7 per 10(5) (95% confidence interval (CI) 2.0-3.5). Of the 57 cases, 39 were Chinese and 18 non-Chinese (7 Vietnamese refugees, 6 Caucasians, 5 others). The annual incidence in Vietnamese refugees less than 5 years old was 42.7 per 10(5) (95% CI 17.2-87.9), giving a relative risk of 18.5 (95% CI 8.3-41.0). Chinese patients (68%) were under-represented as Chinese accounted for at least 94% of the population. Moreover, 14 of the 39 Chinese patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients (p = 0.022).

Child↗

Evaluation of water-equivalent plastics as phantom material for electron-beam dosimetry.

This investigation evaluated samples of three phantom materials designed as substitutes for water for electron beam calibration and depth ionization measurements. Two of the materials are commercially available (photon-electron Solid Water and Plastic Water), while the third (Homat) is not. Applying the values for water for all factors used in the calibration protocol of the American Association of Physicists in Medicine [Task Group 21, Med. Phys. 10, 741-771 (1983)] results in a discrepancy in calculated peak dose rates. Eliminating this discrepancy requires the additional inclusion of a multiplicative correction factor of approximately 1.015 for beam energies below 10 MeV, 1.01 for beam energies between 10 and 12 MeV, and 1.005 for beam energies above 12 MeV. Measurements for R50 and extrapolated range may be made in these materials with no corrections. Some improvement can be made in the performance of the phantom material by optimizing the match to water specifically for electron beams without regard for photon beam response. As with all radiation oncology apparatus, calibration phantoms need acceptance testing before routine use.

Electrons↗

Translational efficiency of gonadotropin-releasing hormone messenger ribonucleic acid is negatively regulated by phorbol ester in GT1-7 cells.

Our laboratory and others have reported that treatment of GT1-7 cells with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), inhibits transcription of the pro-GnRH gene and decreases messenger RNA (mRNA) levels. We were interested in whether translation of the existing GnRH mRNA decreases in parallel with these other indexes of biosynthesis after PMA treatment. GT1-7 cells were treated with PMA (100 nM) or vehicle for 0, 1, or 4 h. The cytosolic ribosome-associated RNA was isolated and layered on a continuous (10-40%) sucrose gradient, and fractions were analyzed for the distribution of ribosome-associated GnRH mRNA through the gradient by ribonuclease protection assay. The mRNA found in the lighter fractions is associated with fewer ribosomes per RNA, suggesting that these fractions are translated less efficiently, and RNA recovered from heavier fractions has a higher number of ribosomes per mRNA, representing mRNA that is more actively translated. We found that the distribution of the ribosome-associated GnRH mRNA was shifted into lighter fractions (i.e. fewer ribosomes per mRNA) after PMA treatment, indicating that a decrease in the translational efficiency of GnRH mRNA occurs after PMA treatment. Thus, PMA exerts inhibitory effects on translation of GnRH mRNA as well as on gene transcription, mRNA stability, and mRNA levels.

Animals↗