Biomedical subjects

A Lin

Publications and source records attributed to A Lin.

At least 109 records · Page 6Linked to original sources

PubMed1998

The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety.

There is some evidence that, in humans and experimental animals, psychological stress may suppress or enhance immune functions, depending on the nature of the stressor and the immune variables under consideration. The possibility that psychological stress may affect the production of pro-inflammatory and immunoregulatory cytokines was investigated in 38 medical students, who had blood samplings a few weeks before and after as well as one day before an academic examination. Psychological stress significantly increased the stimulated production of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-1 receptor antagonist (IL-1Ra), interferon gamma (IFN-gamma) and IL-10. Students with high stress perception during the stressful condition had a significantly higher production of TNF-alpha, IL-6, IL-1Ra and IFN-gamma than students with a low-stress perception. Students with a high anxiety response had a significantly higher production of IFN-gamma and a lower production of the negative immunoregulatory cytokines, IL-10 and IL-4, than students without anxiety. These findings suggest that, in humans, changes in the production of the pro-inflammatory cytokines, TNF-alpha, IL-6 and IFN-gamma, and negative immunoregulatory cytokines, IL-10 and IL-4, take part in the homeostatic responses to psychological stress and that stress-induced anxiety is related to a T-helper-1-like response.

Adult↗

PubMed1998

Serotonin-immune interactions in elderly volunteers and in patients with Alzheimer's disease (DAT): lower plasma tryptophan availability to the brain in the elderly and increased serum interleukin-6 in DAT.

The aims of this study were to examine the plasma availability of tryptophan, the precursor of 5-hydroxytryptamine (5-HT), and serum cytokines, such as interleukin-6 (IL-6) and IL-8, in normal elderly volunteers and in patients with Alzheimer's disease (DAT). Elderly normal volunteers (mean age = 78.3 +/- 5.7 years) had a significantly lower tryptophan/competing amino acids (valine + leucine + isoleucine + phenylalanine + tyrosine) ratio than younger subjects (mean age = 32.9 +/- 8.1 years). In normal volunteers, there were significant and inverse relationships between age and either plasma tryptophan or the tryptophan/competing amino acids ratio, and between the availability of tryptophan to the brain and serum IL-6 or IL-8. DAT patients had significantly higher serum IL-6, but not IL-8, than age-matched normal volunteers. There were no significant differences in the availability of tryptophan to the brain between DAT patients and age-matched normal volunteers. The results suggest that: 1) in normal humans, the availability of plasma tryptophan to the brain decreases with age, and with activation of the immune system; and 2) increased production of IL-6 may play a role in the pathogenesis of DAT.

Adult↗

PubMed1998

The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression.

BACKGROUND: It is now well established that major depression is accompanied by an immune-inflammatory system response and that indicators of the latter are inversely correlated with lower availability of plasma tryptophan in depression. Inflammation and infection can alter sleep architecture, whereas sleep disturbances can impair immune functions. AIMS AND METHODS: The aims of the present study were to examine: (i) immune-inflammatory markers, i.e. serum interleukin-6 (IL-6), IL-8, IL-6 receptor (IL-6R), IL-1R antagonist (IL-1RA), gp130, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood and the availability of plasma tryptophan in patients with primary sleep disorders, major depression and healthy volunteers; and (ii) the relationships between the availability of tryptophan and indicators of the immune-inflammatory response system. RESULTS: Mitogen-stimulated release of PGE2, and serum IL-6 and IL-8, were significantly increased in both depressed and sleep disordered patients compared to normal controls. Serum IL-1RA was significantly higher in depressed patients than in normal controls. Patients with depression and sleep disorders had a significantly lower availability of tryptophan than normal controls. There were significant and inverse relationships between the availability of plasma tryptophan and serum IL-1RA, IL-6 and IL-8. CONCLUSIONS: The results suggest that (i) there is an activation of the immune-inflammatory response system in primary sleep disorders and depression; and (ii) the decreased availability of plasma tryptophan may be related to the inflammatory system response.

Adult↗

PubMed1998

Effects of psychological stress on serum prolyl endopeptidase and dipeptidyl peptidase IV activity in humans: higher serum prolyl endopeptidase activity is related to stress-induced anxiety.

There is now some evidence that psychiatric disorders, such as major depression, schizophrenia and post-traumatic stress disorder are associated with significant alterations in the serum activity of peptidases, such as prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV). The aims of the present study were to examine the effects of psychological stress on serum PEP and DPP IV activity in humans. Thirty-eight university students had repeated measurements of serum PEP and DPP IV activity a few weeks before and after (baseline conditions) as well as the day before a difficult academic examination (stress condition). Subjects were divided into anxiety responders and nonresponders to stress according to their stress-induced increase in the Spielberger State Anxiety Inventory. Serum PEP activity was somewhat lowered by stress in female, but not male, students. Serum PEP activity was significantly higher in the two baseline conditions and during the stress condition in anxiety responders than in anxiety nonresponders. There were no significant effects of stress on serum DPP IV activity and no significant differences between anxiety responders and nonresponders. Serum PEP and DPP IV activity were significantly higher in men than in women. The results suggest that increased baseline serum PEP activity is related to stress-induced anxiety.

Adult↗

PubMed1998

Characterization of a novel DNA binding domain within the amino-terminal region of the RAG-1 protein.

Rag-1 and Rag-2 are the critical components of the V-(D)-J recombinase required for site-specific recombination of the antigen receptor genes. In this study, we have examined the ability of recombinant (r) Rag-1 and Rag-2 to bind the recombination signal sequences (RSS) and have determined that rRag-1, but not rRag-2, is able to directly bind DNA. rRAG-1 DNA binding activity was found to reside within a novel amino-terminal arginine-rich (RR) domain with partial homology to a variety of nucleic acid binding domains. Although the RR-domain did not demonstrate RSS-specificity, this DNA binding domain may stabilize the interaction of RAG-1 with, or increase the affinity for, the V-(D)-J recombination signals.

Amino Acid Sequence↗

PubMed1998

Effect of pterygium excision on induced corneal topographic abnormalities.

PURPOSE: To determine the effect of successful pterygium surgery on astigmatism and other corneal topographic indices. METHODS: Preoperative and postoperative refraction and corneal-topography analysis were performed on 16 consecutive eyes of 12 patients who underwent successful pterygium surgery, with statistical comparison of the pre- and postoperative visual acuity, refractive astigmatism, topographic astigmatism, Surface-Regularity Index, and Surface-Asymmetry Index. RESULTS: Successful pterygium surgery caused statistically significant improvements in visual acuity, refractive and topographic astigmatism, the Surface-Regularity Index, and the surface asymmetry index. CONCLUSION: Corneal-topography analysis is an important component of the evaluation of patients with pterygium, revealing significant abnormalities that are improved by successful removal of the pterygium.

Astigmatism↗

PubMed1998

Correlation between pterygium size and induced corneal astigmatism.

PURPOSE: Before invasion of the visual axis, pterygia typically induce with-the-rule astigmatism, which can be visually significant. In this study, we attempted to assess the quantitative relation between pterygium size and induced corneal astigmatism using corneal topography and digital imaging. METHODS: Thirty-three eyes of 25 patients with primary pterygia were evaluated using corneal topography (TMS), slit-lamp photography, and digital imaging to correlate parameters of pterygium size with induced corneal astigmatism at the 3- and 6-mm optical zones. RESULTS: Pterygia induce asymmetric with-the-rule astigmatism. Lesions extending >45% of the corneal radius or within 3.2 mm of the visual axis produce increasing degrees of induced astigmatism. CONCLUSION: Once pterygia reach a critical size, they induce visually significant central with-the-rule astigmatic changes that may not be apparent by subjective refraction. This finding helps to identify those patients who may benefit from surgical intervention.

Astigmatism↗

PubMed1998

Electroacupuncture decreases c-fos expression in the spinal cord induced by noxious stimulation of the rat bladder.

PURPOSE: The present study investigated the effects of noxious stimulation of the lower urinary tract on neuronal fos protein expression in the spinal micturition center of rats and also examined the effects of electroacupuncture (EA) on fos expression induced by noxious stimulation of the lower urinary tract. MATERIALS AND METHODS: Experiments were conducted on 21 female Sprague-Dawley rats divided into four groups. Group 1 rats (n = 5) served as normal controls. Group 2 rats (n = 5) received EA at the Sanyinjiao acupoint. Group 3 animals (n = 6) were catheterized through the urethra and instilled with 1% acetic acid, and group 4 (n = 5) animals received EA 1 hour before 1% acetic acid instillation. All animals underwent arterial perfusion, laminectomy, and spinal cord removal. Spinal cords were sectioned and processed for immunohistochemical staining for fos protein. RESULTS: No fos protein was detected in any spinal neurons in normal control animals, and either none or few (0 to 4 cells/section) fos-immunoreactive (fos-IR) cells were seen in animals treated with EA. Noxious stimulation of the lower urinary tract with 1% acetic acid drastically increased the number of fos-IR neurons (30 to 127 cells/L6 section, mean 76.17+/-13.98; 28 to 77, cells/S1 section, mean 59+/-8.30; 7 to 35 cells/S2 section, mean 19.83+/-4.10). However, EA administered 1 hour before 1% acetic acid instillation significantly decreased the number of fos-IR neurons resulting from chemical irritation (0 to 50 cells/L6 section, mean 19.8+/-9.33; 0 to 47 cells/S1 section, mean 13.2+/-9.12; 0 to 37 cells/S2 section, mean 13.6+/-7.31). CONCLUSIONS: Our study demonstrates that bladder instillation with 1% acetic acid induces fos protein expression in the spinal micturition center of the rat and that electroacupuncture can reduce this expression. These results suggest a link between electroacupuncture and reduction in spinal neuronal cell activity.

Acetic Acid↗

PubMed1998

Mucin secretion in inflammatory bowel disease: comparison of a macrophage-derived mucin secretagogue (MMS-68) to conventional secretagogues.

We have described a novel macrophage-derived mucin secretagogue (MMS-68) that mediates mucin secretion in colon cancer cell lines and explants of normal and inflammatory bowel disease (IBD) mucosa. We compared MMS-68 induced mucin release with other known intestinal mucin secretagogues in normal colon explants and in the HT-29 colon cancer cell line, and to study the effects of MMS-68 on mucin release from inflamed and uninflamed ulcerative colitis (UC) and Crohn's disease (CD) mucosa. In normal colonic explants and HT-29 cells, each of the secretagogues including, MMS-68-induced mucin release two- to fivefold more than culture medium alone. In HT-29 cells, MMS-68 plus leukotriene C4 (LTC4) induced a 50% increase in mucin release over either secretagogue alone, and MMS-68 plus platelet-activating factor (PAF) markedly enhanced mucin release by eightfold over either secretagogue. In colonic explants from patients with UC and CD, the mucin release in response to MMS-68 was similar to that of normal colonic explants. Likewise, in isolated epithelial cells from CD and UC (whether involved or uninvolved), MMS-68-induced release was similar to that of epithelial cells isolated from normal colonic mucosa. The number of MMS-68-producing macrophages was lower in uninflamed UC mucosa compared with inflamed UC mucosa and CD mucosa. The mucin secretagogue activity of MMS-68 is comparable to that of other known secretagogues, and PAF can have a synergistic effect on this activity. Whole tissue explants and isolated colonic epithelial cells from patients with IBD respond at least as well as their normal counterparts to MMS-68. MMS-68 may play a role in mucin secretion in normal and inflamed colonic tissue.

Carbachol↗

PubMed1998

Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity.

Previous research has revealed that major depression is accompanied by disorders in excitatory amino acids, e.g. glutamate and aspartate, and alterations in serum levels of other amino acids, e.g. serine, glycine and taurine. The aim of the present study was to examine serum levels of aspartate, asparagine, glutamate, glutamine, serine, glycine, threonine, histidine, alanine, taurine and arginine in major depression patients with treatment-resistant depression (TRD). No significant differences in the serum concentrations of any of the above amino acids could be found between patients with and without TRD and normal controls. Non-responders to treatment with antidepressants during a period of 5 weeks were characterized by significantly lower serum levels of aspartate, asparagine, serine, threonine and taurine. A 5-week period of treatment with antidepressants significantly reduced the serum levels of aspartate, glutamate and taurine, and significantly increased the serum concentrations of glutamine. The results suggest that alterations in serum levels of aspartate, asparagine, serine, threonine and taurine may predict the subsequent response to treatment with antidepressants, and that the latter may modulate serum levels of excitatory amino acids and taurine.

Adult↗

PubMed1998

Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia.

There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, as assessed by means of 24-h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post-traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24-h UC excretion. The aim of the present study was to examine 24-h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24-h UC excretion than normal controls and fibromyalgia patients. At a threshold value of > or = 240 micrograms/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24 h UC excretion with a specificity of 100%. There were no significant differences in 24-h UC excretion either between fibromyalgia patients and normal controls, or between patients with major depression and PTSD patients. In the three patient groups, no significant correlations were found between 24-h UC excretion and the HDRS score. In fibromyalgia, no significant correlations were found between 24-h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24-h UC excretion and severity of either depression-avoidance or anxiety-arousal symptoms. In conclusion, this study found increased 24-h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24-h UC were found.

Adult↗

PubMed1998

Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase.

IkappaB kinases (IKKalpha and IKKbeta) are key components of the IKK complex that mediates activation of the transcription factor NF-kappaB in response to extracellular stimuli such as inflammatory cytokines, viral and bacterial infection, and UV irradiation. Although NF-kappaB-inducing kinase (NIK) interacts with and activates the IKKs, the upstream kinases for the IKKs still remain obscure. We identified mitogen-activated protein kinase kinase kinase 1 (MEKK1) as an immediate upstream kinase of the IKK complex. MEKK1 is activated by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 and can potentiate the stimulatory effect of TNF-alpha on IKK and NF-kappaB activation. The dominant negative mutant of MEKK1, on the other hand, partially blocks activation of IKK by TNF-alpha. MEKK1 interacts with and stimulates the activities of both IKKalpha and IKKbeta in transfected HeLa and COS-1 cells and directly phosphorylates the IKKs in vitro. Furthermore, MEKK1 appears to act in parallel to NIK, leading to synergistic activation of the IKK complex. The formation of the MEKK1-IKK complex versus the NIK-IKK complex may provide a molecular basis for regulation of the IKK complex by various extracellular signals.

Animals↗

PubMed1998

Notch inhibition of E47 supports the existence of a novel signaling pathway.

E47 is a widely expressed transcription factor that activates B-cell-specific immunoglobulin gene transcription and is required for early B-cell development. In an effort to identify processes that regulate E47, and potentially B-cell development, we found that activated Notch1 and Notch2 effectively inhibit E47 activity. Only the intact E47 protein was inhibited by Notch-fusion proteins containing isolated DNA binding and activation domains were unaffected-suggesting that Notch targets an atypical E47 cofactor. Although overexpression of the coactivator p300 partially reversed E47 inhibition, results of several assays indicated that p300/CBP is not a general target of Notch. Notch inhibition of E47 did not correlate with its ability to activate CBF1/RBP-Jkappa, the mammalian homolog of Suppressor of Hairless, a protein that associates physically with Notch and defines the only known Notch signaling pathway in drosophila. Importantly, E47 was inhibited independently of CBF1/RPB-Jkappa by Deltex, a second Notch-interacting protein. We provide evidence that Notch and Deltex may act on E47 by inhibiting signaling through Ras because (i) full E47 activity was found to be dependent on Ras and (ii) both Notch and Deltex inhibited GAL4-Jun, a hybrid transcription factor whose activity is dependent on signaling from Ras to SAPK/JNK.

3T3 Cells↗

PubMed1998

Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy.

c-Jun N-terminal protein kinase (JNK) and p38, two distinct members of the mitogen-activated protein (MAP) kinase family, regulate gene expression in response to various extracellular stimuli, yet their physiological functions are not completely understood. In this report we show that JNK and p38 exerted opposing effects on the development of myocyte hypertrophy, which is an adaptive physiological process characterized by expression of embryonic genes and unique morphological changes. In rat neonatal ventricular myocytes, both JNK and p38 were stimulated by hypertrophic agonists like endothelin-1, phenylephrine, and leukemia inhibitory factor. Expression of MAP kinase kinase 6b (EE), a constitutive activator of p38, stimulated the expression of atrial natriuretic factor (ANF), which is a genetic marker of in vivo cardiac hypertrophy. Activation of p38 was required for ANF expression induced by the hypertrophic agonists. Furthermore, a specific p38 inhibitor, SB202190, significantly changed hypertrophic morphology induced by the agonists. Surprisingly, activation of JNK led to inhibition of ANF expression induced by MEK kinase 1 (MEKK1) and the hypertrophic agonists. MEKK1-induced ANF expression was also negatively regulated by expression of c-Jun. Our results demonstrate that p38 mediates, but JNK suppresses, the development of myocyte hypertrophy.

Animals↗

PubMed1998

Novel aspects of the regulation of glycogen storage.

The storage polysaccharide glycogen is widely distributed in nature, from bacteria to mammals. Study of its regulated accumulation has resulted in the discovery or elaboration of several important biochemical principles. Many aspects of the control of glycogen storage still remain poorly understood and glycogen metabolism continues to provide interesting models of more general relevance.

Animals↗

PubMed1998

[Treating portal hypertension by subtotal splenectomy with retroperitoneal splenic transposition and devascularization: clinical study].

OBJECTIVE: To devise a new surgical procedure for improving the operative effect of portal hypertension caused by hepatic cirrhosis. METHOD: In treatment group, subtotal splenectomy with retroperitoneal transposition was performed in 36 patients of cirrhotic hypertensives. In control group, 36 patients were treated by devascularization. The follow-up period ranged from 3 months to 5.5 years (average 26 months). RESULT: In the treatment group, the rates of disappearance, improvement and absence of changes of esophageal varices were 11.5%, 61.5% and 26.9%, respectively, and in the control group those of improvement were 50.0%, absence of change 45.8% and aggravation 4.2%. There was a significant difference between them (P < 0.05). In the treatment group, hypersplenism disappeared in all. There was also significant difference between the two groups in immunological indexes (P < 0.05). DSA showed abundant collateral circulation in the residual spleen and retroperitoneal wall, which enabled the portal blood flow diverting to retroperitoneal tissues. CONCLUSION: This method possesses the advantages of devascularization and decompression shunt. It is of value in retaining part of spleen in surgical treatment of portal hypertension.

Female↗

PubMed1998

Alcaligenes xylosoxidans keratitis post penetrating keratoplasty in a rigid gas permeable lens wearer.

PURPOSE: We report a case of Alcaligenes xylosoxidans keratitis following penetrating keratoplasty in a rigid gas permeable (RGP) lens wearer. METHODS: A 61 year old RGP lens wearer with a history of nonresponsive keratitis of the right eye which involved the graft margin was referred to us for treatment. Corneal cultures revealed growth of a gram-negative rod on the fifth day and the organism was subsequently identified as Alcaligenes xylosoxidans, which was resistant to most antibiotics and sensitive only to Bactrim, Timentin, and imipenem. RESULTS: Clinical improvement was observed within 24 hours after treatment with the use of topical i.v. Bactrim and topical i.v. Timentin 2% alternating every 30 minutes. Complete resolution of the infection with mild scarring was observed 6 weeks after treatment. CONCLUSIONS: Alcaligenes xylosoxidans is a potential cause of bacterial keratitis which should be considered in cases of nonresponsive gram-negative keratitis. The addition of topical Bactrim or Timentin may need to be considered in such cases.

Administration, Topical↗

PubMed1997

An HIV type 2 DNA vaccine induces cross-reactive immune responses against HIV type 2 and SIV.

We have previously reported on the generation of specific functional immune responses after inoculation of animals with expression vectors encoding HIV-1 genes. This article provides the details of the first application of this new technology to induce immune responses against HIV-2. This virus is molecularly and serologically distinct from HIV-1 and is in fact more closely related to the simian immunodeficiency virus (SIV). Anti-HIV-2 and SIV antibodies were induced in mice of three different haplotypes following a single intramuscular inoculation with an HIV-2/ROD envelope glycoprotein expression vector (pcEnv-2). Boosting of animals with pcEnv-2 induced both anti-HIV-2 neutralizing antibodies and T cell-proliferative responses against HIV-2 and SIVmac proteins. We compared the humoral and cellular immune responses of mice injected with pcEnv-2 and then boosted with either the homologous DNA construct or a recombinant Env protein. Animals boosted with pcEnv-2 generated B and T cell immune responses as strong as those of mice boosted with recombinant gp140 protein in adjuvant. Finally, cellular immune responses were significantly increased with the coadministration of pcEnv-2 and a plasmid expressing interleukin 12. We therefore conclude that DNA plasmid inoculation induces cross-reactive anti-HIV-2 and anti-SIVmac immune responses in mice. This technology should be further investigated as a potential vaccine component for this human pathogen.

AIDS Vaccines↗