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Biomedical subjects

A Ho

Publications and source records attributed to A Ho.

At least 73 records · Page 4Linked to original sources
PubMed1999

CD28-deficient mice are highly resistant to collagen-induced arthritis.

CD28 provides a critical costimulatory signal in Ag-specific T cell activation. Recent studies have revealed an important role for CD28 in the development of autoimmune diseases. We have examined the role of CD28 in collagen-induced arthritis (CIA) by inducing CIA in CD28-deficient DBA/1 mice. CD28-deficient mice never developed arthritis and showed markedly decreased levels of IgG and IgM anti-type II collagen (CII) Abs. In addition, the CD28+/- mice had similar levels of IgG1 and IgG2a anti-CII Abs, whereas in the CD28-deficient mice the level of IgG1 anti-CII Abs was decreased compared with that of IgG2a. IFN-gamma production by lymph node cells in response to CII was also reduced. CD28-deficient mice were either immunized four times with CII in CFA to augment Ag loading or given low doses of IL-12 to enhance Thl type responses. Both treatments resulted in a very low incidence of CIA development and minimal disease. CD28-deficient mice developed arthritis from injection of lymph node cells from CII-immunized wild-type mice, followed by immunization with CII in CFA. Taken together, these results indicate that costimulation of CD28 cannot be replaced by repeated activation through TCR or other costimulatory molecules. Thus, CD28 plays a critical role in both cellular and humoral immunity against CII and is indispensable for the development of CIA.

Adoptive Transfer↗
PubMed1999

Estrous cycle differences in cocaine-induced stereotypic and locomotor behaviors in Fischer rats.

This study was conducted to characterize female behavioral response to acute 'binge' pattern cocaine administration (15 mg kg(-1) i.p., three times a day, at 1 h intervals) during the different stages of the estrous cycle in Fischer rats. Cocaine administration significantly increased stereotypic behavior and locomotion in females. Animals in estrus showed significantly higher cocaine-induced stereotypic and locomotive behavioral responses than those in other stages of the cycle. Plasma levels of the cocaine metabolite benzoylecgonine during metestrus diestrus were significantly higher than during estrus and proestrus probably reflecting more rapid biotransformation of cocaine. Therefore, it is likely that the hormonal fluctuations associated with the estrous cycle modulate both cocaine metabolism and the behavioral responses to cocaine in female rats. This in turn may have important implications in gender differences in behavioral responses to cocaine.

Animals↗
PubMed1999

A novel method to quantify the edge contour of RGP contact lenses.

A new method of accurate profile measurement of rigid gas permeable lenses and edges is described. A purpose built optical profilometer non-destructively scans complete cross-sections in several meridians of any rigid lens. The accuracy of the instrument was verified to be better than +/-2.5 microm. The profile data are obtained and stored in digital format for further analysis. The seven most commonly used edge features were defined by means of mathematical algorithms to extract unique numerical values for these parameters from the measured profiles. Applications of the new edge quantification method in clinical contact lens research and manufacturing quality control are shown.

Journal Article↗
PubMed1999

Longitudinal study of predictive factors for periodontal disease and tooth loss.

Longitudinal assessment of risk factors for periodontal disease is necessary to provide evidence that a putative risk factor or risk indicator is a true risk factor. The purpose of the present study was to explore longitudinally a variety of markers as possible periodontal risk factors in subjects with little or no periodontal disease at baseline. 415 subjects with mild or little periodontal disease were examined: medical and dental history; socioeconomic profile, clinical measurements, microbial samples and radiographic assessment of bone height were performed at baseline, and at a follow-up examination 2 to 5 years later. Mean probing pocket depth (PPD) at baseline was 1.99+/-0.37 mm while mean overall change was 0.1 mm which amounts to an annual rate of 0.04 mm. Overall mean clinical attachment level (1.75+/-0.6 mm) at baseline resulted in mean attachment change of 0.28 mm (0.12 mm annually). Alveolar crestal height (ACH) at baseline (mean 2.05+/-0.85 mm) resulting in a mean net loss of 0.1 mm. Approximately 10% of all sites presented for the second visit with attachment loss exceeding the threshold (4.4% annually), while only 2.2% of all sites exhibited attachment gain (0.88% annually). Older individuals exhibited greater mean bone loss but the least amount of attachment loss. Current smokers exhibited greater disease progression compared to non-smokers. Tooth morbidity (0.17 teeth/patient/year) was associated with greater baseline CAL and ACH loss, and an assortment of systemic conditions. Subjects who harbored Bacteroides forsythus (Bf) at baseline had greater loss in ACH; likewise, these subjects experienced greater proportions of losing sites and twice as much tooth mortality compared to Bf-negative patients. Baseline clinical parameters correlated strongly with the outcome, i.e., subjects with deeper mean pocket depth at baseline exhibited greater increase in pocket depth overtime; while subjects with greater attachment loss at baseline exhibited greater attachment loss between the 1st and 2nd visits.

Adult↗
PubMed1999

Methadone-maintained former heroin addicts, including those who are anti-HIV-1 seropositive, comply with and respond to hepatitis B vaccination.

AIMS: To study the efficacy of standard hepatitis B (HB) vaccination in methadone-maintained former intravenous drug users. DESIGN: HB vaccine was administered to subjects at 0, 1 and 6 months. SETTING: Two university-affiliated methadone maintenance clinics. PARTICIPANTS: Forty-three HB-unexposed former heroin addicts in methadone maintenance treatment for heroin addiction. MEASUREMENTS: HB surface antibody (anti-HBs) response to the vaccine was assessed at 0, 1, 6 and > or = 12 months; anti-HIV-1 status was also assessed. FINDINGS: Thirty-seven patients (86%) completed the 6-month vaccination series. Of the 30 anti-HIV-1 seronegative patients who then completed the entire 12-month protocol, 21 (70%) seroconverted (anti-HBs ratio > 2.1) and 19 (63%) were protected (anti-HBs ratio > 10). Two other subjects were anti-HIV-1 seropositive: one was HB-protected at 12 months but later lost immunity. Ten anti-hepatitis C antibody-positive patients completed the 12-month study and six were protected; thus, there was no significant relationship between hepatitis C status and HB vaccine response. CONCLUSIONS: Standard HB vaccination is both feasible and effective.

Adult↗
PubMed1999

Evaluation of the efficacy of a hospital-based asthma education programme in patients of low socioeconomic status in Hong Kong.

BACKGROUND: Good asthma control requires optimal medical treatment in conjunction with appropriate self-management. In the West, the effectiveness of patient education on improving self-management has been well documented. However, data amongst Asian populations are lacking. We performed a pilot study to evaluate the efficacy of a hospital based education programme aimed at improving self-management skills and reducing morbidity in a Chinese population with low socioeconomic status and education level. METHODS: Our asthma education programme was a low-cost programme conducted in essence by specialist respiratory nurses. Patients attending our asthma clinic were instructed during a two-hour educational session on the pathophysiology of asthma, its potential triggers, the appropriate use of medications including proper inhaler techniques, and the self-management of their disease. These instructions were reinforced by video sessions at subsequent outpatient clinic attendance when patients' inhaler and peak flow techniques were checked by the same nurses and their self-management plan re-examined by the attending physicians. Asthma knowledge, inhaler technique, FEV1 and peak expiratory flow (PEF), and patients' self-rating of their asthma were determined at baseline, 6 months and 1 year after the intervention. Morbidity was assessed by the numbers of hospitalizations, unscheduled visits to family physicians and accident and emergency department attendance, courses of oral steroid used and days off work or school at baseline and 1 year. RESULTS: Two hundred and thirty patients were recruited for the study, 83% completing the entire assessment period. The group demonstrated significant improvements in lung function: the mean FEV1 +/- SD increased from 63.6 +/- 20.6% of predicted values at baseline to 68.5 +/- 22.3% at 6 months and 68.6 +/- 22.8% at 1 year (P < 0.05), and the mean PEF +/- SD increased from 64.6 +/- 23.0% of predicted values at baseline to 75.4 +/- 27.0% at 6 months and 76.8 +/- 24.5% at 1 year(P < 0.001). There were also significant improvements in inhaler technique (P < 0.01), asthma knowledge (P < 0.001), patients' self-rating of their asthma (P < 0.05), and reductions in the numbers of hospitalizations (P < 0.01), visits to family physicians (P < 0.001) and accident and emergency department attendance (P < 0.001) during the study period. Patients with moderate to severe asthma as defined by an FEV1 of < 80% of predicted values were most likely to benefit from the programme. CONCLUSIONS: We conclude that patient education is likely to be an essential component in the holistic approach to the management of asthma even amongst Asian populations of low socioeconomic status and education level. Further studies using randomised controlled trials are necessary to consolidate our findings.

Administration, Oral↗
PubMed1999

Regulation of the heparan sulfate proteoglycan, perlecan, by injury and interleukin-1alpha.

Perlecan is a specific proteoglycan that binds to amyloid precursor protein and beta-amyloid peptide, is present within amyloid deposits, and has been implicated in plaque formation. Because plaque formation is associated with local inflammation, we hypothesized that the mechanisms involved in brain inflammatory responses could influence perlecan biosynthesis. To test this hypothesis, we first studied perlecan regulation in mice after inflammation induced by a brain stab wound. Perlecan mRNA and immunoreactivity were both increased 3 days after injury. Interleukin-1alpha (IL-1alpha) is a cytokine induced after injury and plays an important role in inflammation. As such, IL-1alpha may be one of the factors participating in regulating perlecan synthesis. We thus studied perlecan regulation by IL-1alpha, in vivo. Regulation of perlecan mRNA by this cytokine was area-specific, showing up-regulation in hippocampus, whereas in striatum, perlecan mRNA was unchanged. To support this differential regulation of perlecan mRNA by IL-1alpha, basic fibroblast growth factor (bFGF), a growth factor also present in plaques, was studied in parallel. bFGF mRNA did not show any regional difference, being up-regulated in both hippocampus and striatum in vivo. In vitro, both astrocyte and microglia were immunoreactive for perlecan. Moreover, perlecan mRNA was increased in hippocampal glial cultures after IL-1alpha but not in striatal glia. These results show an increase in perlecan biosynthesis after injury and suggest a specific regulation of perlecan mRNA by IL-1alpha, which depends on brain area. Such regulation may have important implications in the understanding of regional brain variations in amyloid plaque formation.

Alzheimer Disease↗
PubMed1999

Mutilating facial sarcoidosis.

We report a patient with massive facial sarcoidosis. While skin involvement is a common manifestation of sarcoidosis, it is unusual to see it in the dramatic form of cutaneous tumors with mutilation of the central face. There are few reports of tumoral cutaneous sarcoidosis like that of our patient.

Adult↗
PubMed1999

Effects of chronic 'Binge' cocaine administration on plasma ACTH and corticosterone levels in mice deficient in DARPP-32.

The product of the DARPP-32 gene mediates intracellular signals initiated by the binding of dopamine to its receptors. Cocaine administration leads to increased activation of dopamine receptors, and causes activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis. We determined the effects of chronic 'binge' pattern cocaine on HPA activity in mice containing a targeted disruption of the DARPP-32 gene. Mice received three daily injections of cocaine (15 mg/kg/injection) for 14 days, and were sacrificed 30 min after the last injection. We measured the levels of plasma adrenocorticotropin (ACTH) and corticosterone which reflect HPA activity. In wild-type controls, 'binge' cocaine administration significantly increased plasma ACTH and corticosterone levels. In contrast, DARPP-32-deficient mice failed to show a significant elevation of either plasma ACTH or corticosterone levels following 'binge' cocaine. The results indicate that DARPP-32 plays a role in mediating the stimulatory effects of cocaine on the HPA axis.

Adrenocorticotropic Hormone↗
PubMed1999

Cocaine abuse sharply reduced in an effective methadone maintenance program.

A comprehensive study of an urban methadone clinic with supervised urine analyses for illicit drugs was conducted over an 18 month period for a 133 patient cohort as they entered or remained in methadone maintenance for narcotic addiction. Overall retention during the study was 85%, with significantly (p < .05) higher daily methadone doses (mean 67.1 mg +/- 2.1) in those patients still in treatment at the end of the study. Predictably, illicit opioid use was dramatically reduced, to 10% as measured by urine toxicology in the last month of treatment. Moreover, significantly more patients stopped regular cocaine abuse (69%) than started using cocaine (10%, Fisher's exact test, p = .02). Thus, with effective methadone maintenance using adequate dosages, the majority of patients remain in treatment and reduce cocaine abuse as well as illicit opioid use, with implications for public health by reducing the spread of infectious diseases including hepatitis B, C, D and human immunodeficiency virus (HIV-1).

Adult↗
PubMed1999

Hypothalamic-pituitary-adrenal activity and pro-opiomelanocortin mRNA levels in the hypothalamus and pituitary of the rat are differentially modulated by acute intermittent morphine with or without water restriction stress.

Acute administration of morphine stimulates the secretion of hypothalamic-pituitary-adrenal (HPA) hormones, ACTH, beta-endorphin and corticosterone in the rat. In this study we investigated the effects of repeated multiple-dose morphine on HPA activity under two different conditions: without or with water restriction stress. Rats received six intermittent injections of morphine (6.25 mg/kg per injection, s.c.) every 2 h and were killed 30 min after the last injection. The results were as follows. (1) Morphine significantly elevated plasma ACTH and corticosterone levels; water restriction also significantly increased ACTH secretion, but with no significant increase of plasma corticosterone levels. In contrast, rats treated with morphine under the water restriction condition failed to show any increases of either ACTH or corticosterone levels. (2) Morphine did not change pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary; whereas water restriction significantly increased the POMC mRNA levels. The water restriction-induced increases of POMC mRNA in the anterior pituitary were absent in the rats which received morphine. (3) Morphine significantly increased POMC mRNA levels in the hypothalamus; water restriction had no effect. The morphine-induced increases in POMC mRNA in the hypothalamus were absent in the rat under the water restriction condition. These findings, that the effects of morphine on HPA activation or POMC mRNA expression depend on the presence of stress, suggest a counter-regulatory role of opiates on a stress response and opioid gene expression.

Adrenocorticotropic Hormone↗
PubMed1999

Dynorphin A1-13 causes elevation of serum levels of prolactin through an opioid receptor mechanism in humans: gender differences and implications for modulation of dopaminergic tone in the treatment of addictions.

Dynorphin peptides act preferentially at kappa- as well as mu- and delta-opioid receptors. This study was conducted to determine whether dynorphin peptides act to lower dopaminergic tone in the tuberoinfundibular system, resulting in elevated serum prolactin levels and, if so, whether such an effect is mediated by the opioid receptors. Dose-related increases in serum prolactin levels were observed after dynorphin A1-13 was administered i.v. in doses of 120 and 500 micrograms/kg to healthy human volunteers with no history of drug or alcohol abuse. Studies were then conducted to determine whether this effect is opioid receptor mediated and, if so, whether at kappa- or mu types. Pretreatment with the opioid antagonist nalmefene (30 mg i.v.), which has high affinity at both mu- and kappa-opioid receptors, caused a greater attenuation in dynorphin A1-13-stimulated increases in serum prolactin levels than pretreatment with similarly high doses of naloxone, an antagonist with lower affinity for both mu- and kappa-opioid receptors. These results suggest dynorphin A1-13 lowers tuberoinfundibular dopaminergic tone through action at kappa- and possibly mu-opioid receptors. Female subjects were significantly more responsive to the prolactin effects of dynorphin than were male subjects. Dynorphin gene expression, dynorphin peptides, and kappa-opioid receptor gene expression and binding have been shown to be altered in response to cocaine administration. Also, both dynorphin peptides and synthetic kappa-opioid agonists have been shown to lower dopamine levels in the nucleus accumbens and to attenuate cocaine-induced surges in dopamine levels. Thus, a dynorphin-like compound capable of reaching critical mesolimbic-mesocortical and nigrostriatal dopaminergic systems may be effective in the management of cocaine addiction.

Adult↗
PubMed1998

High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice.

BACKGROUND: Germ-line and sporadic mutations in the tumor suppressor gene PTEN (also known as MMAC or TEP1), which encodes a dual-specificity phosphatase, cause a variety of cancers such as Cowden disease, glioblastoma, endometrial carcinoma and prostatic cancer. PTEN is widely expressed, and Cowden disease consistently affects various organ systems, suggesting that the PTEN protein must have an important, although as yet poorly understood, function in cellular physiology. RESULTS: Homozygous mutant mice lacking exons 3-5 of the PTEN gene (mPTEN3-5) had severely expanded and abnormally patterned cephalic and caudal regions at day 8.5 of gestation. Embryonic death occurred by day 9.5 and was associated with defective chorio-allantoic development. Heterozygous mPTEN3-5 mice had an increased incidence of tumors, especially T-cell lymphomas; gamma-irradiation reduced the time lapse of tumor formation. DNA analysis of these tumors revealed the deletion of the mPTEN gene due to loss of heterozygosity of the wild-type allele. Tumors associated with loss of heterozygosity in mPTEN showed elevated phosphorylation of protein kinase B (PKB, also known as Akt kinase), thus providing a functional connection between mPTEN and a murine proto-oncogene (c-Akt) involved in the development of lymphomas. CONCLUSIONS: The mPTEN gene is fundamental for embryonic development in mice, as mPTEN3-5 mutant embryos died by day 9.5 of gestation, with patterning defects in cephalic and caudal regions and defective placentation. Heterozygous mice developed lymphomas associated with loss of heterozygosity of the wild-type mPTEN allele, and tumor appearance was accelerated by gamma-irradiation. These lymphomas had high levels of activated Akt/PKB, the protein product of a murine proto-oncogene with anti-apoptotic function, associated with thymic lymphomas. This suggests that tumors associated with mPTEN loss of heterozygosity may arise as a consequence of an acquired survival advantage. We provide direct evidence of the role of mPTEN as a tumor suppressor gene in mice, and establish the mPTEN mutant mouse as an experimental model for investigating the role of PTEN in cancer progression.

Animals↗
PubMed1998

Induction of interleukin-1 associated with compensatory dopaminergic sprouting in the denervated striatum of young mice: model of aging and neurodegenerative disease.

Young mice challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which selectively destroys the substantia nigra dopaminergic neurons in the midbrain, exhibit spontaneous recovery of dopaminergic nerve terminals. However, such recovery becomes attenuated with age. Here we report that newly sprouted fibers originate from spared dopaminergic neurons in the ventral tegmental area. We found that interleukin-1 (IL-1), an immune response-generated cytokine that can enhance dopaminergic sprouting when exogenously applied, increased dramatically in the denervated striatum of young mice (2 months) compared with middle-aged mice (8 months) after MPTP treatment. Young mice displayed a maximal 500% induction of IL-1alpha synthesis that remained elevated for several weeks in the dorsal and ventral striatum, whereas middle-aged mice exhibited a modest 135% induction exclusively in the dorsal striatum for a week. IL-1alpha immunoreactivity was localized in GFAP-immunoreactive hypertrophied astrocytes and neurons within the denervated striatum of young mice. However, no induction of IL-1alpha mRNA was seen in the midbrain in either age group despite glial activation. Because we have reported that IL-1 can regulate astroglia-derived dopaminergic neurotrophic factors, it was surprising that no changes were observed in acidic and basic fibroblast growth factor or glial cell line-derived neurotrophic factor mRNA levels associated with MPTP-induced plasticity of dopaminergic neurons in the striatum of young mice. Interestingly, we found that dopaminergic neurons express IL-1 receptors, thus suggesting that IL-1alpha could directly act as a target-derived dopaminergic neurotrophic factor to initiate or enhance the sprouting of dopaminergic axonal terminals. These findings strongly suggest that IL-1alpha could play an important role in MPTP-induced plasticity of dopaminergic neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Effects of memantine alone and with acute 'binge' cocaine on hypothalamic-pituitary-adrenal activity in the rat.

The effects of memantine, a non-competitive NMDA-receptor antagonist used in the management of dementia, and its coadministration with acute 'binge' pattern cocaine on hypothalamic-pituitary-adrenal axis activity were investigated in the rat. Measurements 3 h after injections showed that memantine alone at 20 mg kg(-1) (i.p.), but not 10 mg kg(-1), increased corticotropin-releasing factor (CRF) mRNA levels in the hypothalamus and both adrenocorticotropic hormone and corticosterone levels in the blood, and decreased type I CRF receptor mRNA in the anterior pituitary. Our previous studies have shown that acute 'binge' cocaine increases CRF mRNA levels in the hypothalamus. In this study, pretreatment with memantine (10 and 20 mg kg(-1), i.p.) did not alter the up-regulation of hypothalamic CRF mRNA induced by acute 'binge' cocaine (3 x 15 mg kg(-1), i.p.). Of interest, pretreatment with memantine at 10 mg kg(-1), which alone had no effect on corticosterone levels, caused a greater elevation of corticosterone levels in combination with 'binge' cocaine than acute 'binge' cocaine alone, indicating that memantine does not attenuate 'binge' cocaine-stimulated hypothalamic-pituitary-adrenal activity. These results indicate that both memantine and acute 'binge' cocaine stimulate hypothalamic-pituitary-adrenal activity by activating CRF neurons in the hypothalamus.

Adrenal Glands↗
PubMed1998

Downregulation of 5-HT1A receptors in rat hypothalamus and dentate gyrus after "binge" pattern cocaine administration.

The effect of chronic cocaine exposure on the central serotonergic system in the rat was investigated using a selective 5-HT1A receptor agonist, [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), and a 5-HT2A receptor antagonist, [3H]ketanserin, as tritiated ligands in a quantitative autoradiography study. Rats were administered cocaine in a "binge" pattern, 15 mg/kg/injection, three times a day, at 1-h intervals for 14 days to mimic the pattern often seen in human cocaine addicts. A significant decrease in the binding of [3H]8-OH-DPAT was found in the ventromedial hypothalamus (P < 0.001) and the dorsal dentate gyrus (P < 0.01) in rats administered cocaine as compared with rats injected with saline. No significant difference in the binding of [3H]ketanserin was found in frontal, parietal, agranular insular, and piriform cortices, caudate-putamen, olfactory tubercle, nucleus accumbens, thalamus, septohippocampal nucleus, and claustrum. Several studies have shown that 5-HT1A receptor agonists have antidepressant properties. Other studies, in animal models, have shown that 5-HT1A receptor agonists stimulate the hypothalamic-pituitary-adrenal axis, which is of interest, since chronic activation of this axis has been related to anxiety and depression. Our data show that the 5-HT1A component of the serotonergic system is altered following chronic "binge" pattern cocaine administration in an animal model and may be related to changes in the HPA axis and behavior.

Animals↗
PubMed1998

Effect of endogenous cortisol levels on natural killer cell activity in healthy humans.

The aim of this study was to examine the effects of increasing and decreasing endogenous cortisol levels on natural killer (NK) cell activity in vivo. Normal healthy volunteers participated in the following studies: baseline (n = 27), metyrapone challenge test (n = 10), dexamethasone suppression test (n = 10), and adrenocorticotropic hormone (ACTH) stimulation test (n = 8). Each subject served as his own control for each study. Each subject was tested for NK activity and plasma cortisol levels at 9 a.m., just before the challenge drug administration, and at 10 a.m., except for the dexamethasone study, in which only the 9 a.m. blood was drawn, 10 h after the dexamethasone administration. On the baseline study day, a significant decrease in plasma cortisol levels was found from 9 to 10 a.m. (p <.02) along with a significant increase in NK activity (p <.001). On the metyrapone test day, plasma cortisol levels at 10 a.m. were significantly reduced (p <.005) as expected, while NK activity at the same time point was not affected and was increased to an extent equivalent to the baseline study day. On the dexamethasone test day, plasma cortisol concentrations were significantly decreased (p <.0001) as compared to the same time point on the baseline day, without any significant change in the NK activity. On the ACTH test day, plasma cortisol rose significantly at 10 a.m. (p <.02), with no change in NK activity. We conclude that plasma cortisol alone has no significant effect on NK activity in vivo.

Adrenocorticotropic Hormone↗