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Biomedical subjects

T J Lin

Publications and source records attributed to T J Lin.

At least 19 recordsLinked to original sources
PubMed2000

Human mast cells transmigrate through human umbilical vein endothelial monolayers and selectively produce IL-8 in response to stromal cell-derived factor-1 alpha.

Mature mast cells are generally considered to be less mobile cells residing within tissue sites. However, mast cell numbers are known to increase in the context of inflammation, and mast cells are recognized to be important in regulating local neutrophil infiltration. CXC chemokines may play a critical role in this process. In this study two human mast cell-like lines, HMC-1 and KU812, and human cord blood-derived primary cultured mast cells were employed to examine role of stromal cell-derived factor-1 (SDF-1) in regulating mast cell migration and mediator production. It was demonstrated that human mast cells constitutively express mRNA and protein for CXCR4. Stimulation of human mast cells with SDF-1, the only known ligand for CXCR4, induced a significant increase in intracellular calcium levels. In vitro, SDF-1 alpha mediated dose-dependent migration of human cord blood-derived mast cells and HMC-1 cells across HUVEC monolayers. Although SDF-1 alpha did not induce mast cell degranulation, it selectively stimulated production of the neutrophil chemoattractant IL-8 without affecting TNF-alpha, IL-1beta, IL-6, GM-CSF, IFN-gamma, or RANTES production, providing further evidence of the selective modulation of mast cell function by this chemokine. These findings provide a novel, SDF-1-dependent mechanism for mast cell transendothelial migration and functional regulation, which may have important implications for the local regulation of mast cells in disease.

Animals↗
PubMed2000

Activation of macrophage CD8: pharmacological studies of TNF and IL-1 beta production.

Previously, we demonstrated that rat macrophages express CD8 and that Ab to CD8 stimulates NO production. We confirm that CD8 is expressed by rat macrophages and extend understanding of its functional significance. Activation of CD8 alpha (OX8 Ab) on alveolar macrophages stimulated mRNA expression for TNF and IL-1 beta and promoted TNF and IL-1 beta secretion. Similarly, OX8 Ab (CD8 alpha) stimulated NR8383 cells to secrete TNF, IL-1 beta, and NO. Activation of CD8 beta (Ab 341) on alveolar macrophages increased mRNA expression for TNF and IL-1 beta and stimulated secretion of TNF, but not IL-1 beta. Interestingly, anti-CD8 Abs did not stimulate IFN-gamma or PGE2 production, or phagocytosis by macrophages. OX8 (CD8 alpha)-induced TNF and IL-1 beta production by macrophages was blocked by inhibitors of protein tyrosine kinase(s), PP1, and genistein, but not by phosphatidylinositol-3 kinase inhibitor, wortmannin. Moreover, OX8 stimulated protein tyrosine kinase activity in NR8383 cells. Further analysis of kinase dependence using antisense to Syk kinase demonstrated that TNF, but not IL-1 beta, stimulation by CD8 alpha is Syk dependent. By contrast, protein kinase C inhibitor Ro 31-8220 had no effect on OX8-induced TNF production, whereas OX8-induced IL-1 beta production was blocked by Ro 31-8220. Thus, there are distinct signaling mechanisms involved in CD8 alpha (OX8)-induced TNF and IL-1 beta production. In summary, macrophages express CD8 molecules that, when activated, stimulate TNF and IL-1 beta expression, probably through mechanisms that include activation of Src and Syk kinases and protein kinase C. These findings identify a previously unknown pathway of macrophage activation likely to be involved in host defense and inflammation.

Androstadienes↗
PubMed2000

Redundancy or cell-type-specific regulation? Tumour necrosis factor in alveolar macrophages and mast cells.

Tumour necrosis factor (TNF) is an important inflammatory cytokine produced by several cell types. To test the hypothesis that there is cell-type-specific regulation and not redundancy of TNF production, we investigated its production by alveolar macrophages (AM) and peritoneal mast cells (PMC). Cell lysates of freshly isolated AM and PMC contained 9 +/- 3 pg and 57 +/- 17 pg of TNF/10(6) cells, respectively. Furthermore, unstimulated PMC expressed 4 x 10(3)-fold more attomols of TNF mRNA/microg total RNA compared with AM. These data may explain in part the greater TNF-dependent cytotoxicity of PMC. Furthermore, fixed PMC showed significantly higher TNF-dependent cytotoxic activity than AM (sevenfold), suggesting that PMC express more membrane TNF than AM. Although AM and PMC contain different amounts of TNF, antigen stimulation caused a similar release of TNF from sensitized rats. Interferon (IFN)-gamma, respectively, stimulated and inhibited AM and PMC TNF-dependent cytotoxicity whereas lipopolysaccharide (LPS) significantly stimulated TNF-dependent cytotoxicity in both cell types. However, TNF released (AM 400-fold and PMC threefold) and TNF mRNA expression, as measured by competitive reverse transcription-polymerase chain reaction (AM 7 x 10(3)-fold and PMC twofold), were considerably greater in LPS-stimulated AM than PMC. Our data indicate that TNF is differentially expressed in these two cell types and that its production is dependent on the nature of the stimulus. These data provide vital basis in experimental approaches aimed at modulating the effect of TNF in airway disease conditions involving both AM and mast cells.

Animals↗
PubMed1999

Internalization of FimH+ Escherichia coli by the human mast cell line (HMC-1 5C6) involves protein kinase C.

Rodent mast cells (MC) play critical roles in host defense against bacterial infection. However, bacteria-mediated signaling mechanisms in MC have not been studied. In addition, the response of human MC to bacteria is not fully investigated. This study examined the interaction between human MC and type 1 fimbriated Escherichia coli and the mechanisms involved using the human MC line HMC-1 5C6 and human cord blood-derived MC. These MC internalized significant numbers of FimH+ E. coli, but not its isogenic FimH- mutant. In HMC-1 cells, bacterial internalization was stimulated by protein kinase C (PKC) activation [short-term phorbol myristate acetate (PMA) treatment] and dramatically decreased by PKC inhibitors or PKC depletion (long-term PMA treatment). Moreover, bacterial internalization was accompanied by significant expression of PKCbeta1 and delta. Fluorescence microscopy demonstrated accumulation of PKCbeta1 on internalized bacteria. These data indicate that human MC has the capacity to internalize bacteria and PKC may be a critical intracellular mediator of this function.

Adhesins, Bacterial↗
PubMed1999

Acute basagran poisoning mimicking neuroleptic malignant syndrome.

A 27-year-old robust man, without any medical and surgical history, attempted to commit suicide by consumption of 300 cc (44.1%, 132.3 g) basagran, a readily available herbicide. This poisoning resulted in vomiting, fever, sweating, pipe-like muscle rigidity, sinus tachycardia, drowsiness, leukocytosis, rhabdomyolysis and hepatorenal damage. Emperical treatment with bromocriptine was temporally associated with resolution of above signs and symptoms. His clinical presentations and the effect of bromocriptine may be indicative that basagran poisoning mimicks neuroleptic malignant syndrome.

Adult↗
PubMed1999

Clinical impact of upper gastrointestinal tract injuries in glyphosate-surfactant oral intoxication.

Fifty patients with glyphosate-surfactant oral ingestion were studied with upper gastrointestinal (UGI) endoscopic grading using Zargar's modified grading system for mucosal corrosive injury. Esophageal injury was seen in 68% of the patients, gastric injury in 72%, and duodenal injury in 16%. There were no grade 3 injuries. The upper gastrointestinal tract injuries caused by glyphosate-surfactant were minor in comparison with those by other strong acids. The WBC count, amount of glyphosate-surfactant ingested, length of hospital stay and the occurrence of serious complications increased markedly in the group which had grade 2 esophageal injuries. Thus, the severity of the esophageal injuries may be a prognostic factor for the patient with glyphosate-surfactant ingestion. The UGI endoscopy may be indicated for grading esophageal injury in patients who have ingested glyphosate-surfactant in amounts greater than 100 ml. Physicians should pay more attention to the patients with grade 2 or 3 esophageal injuries to prevent serious complications and to provide aggressive supportive care.

Administration, Oral↗
PubMed1999

Acute paraquat intoxication: using nuclear pulmonary studies to predict patient outcome.

STUDY OBJECTIVES: Paraquat, a widely used herbicide, has been shown to cause severe and often fatal pulmonary fibrosis in humans and laboratory animals. Although paraquat is known to be directly cytotoxic to lung parenchyma, changes in routine lung scintigraphy results after acute paraquat intoxication have not been reported. The objective of this project was to investigate changes in lung ventilation (LV) and alveolar permeability (AP) in patients with paraquat intoxication, using 99mTc diethylenetriamine pentaacetate (DTPA) radioaerosol lung scintigraphy. DESIGN: Prospective, blinded study. SETTING: Nuclear medicine and toxicology departments in two university-affiliated teaching hospitals. PATIENTS OR PARTICIPANTS: Thirteen patients with acute paraquat intoxication were included in this study. Ten volunteers without acute paraquat intoxication were studied for comparison. MEASUREMENTS AND RESULTS: 99mTc DTPA aerosol inhalation and 99mTc macroaggregated albumin (MAA) perfusion lung scintigraphies were performed to determine LV, AP, and lung perfusion (LP). Five of the 13 patients (38%) had significant LV abnormalities; 3 of these 5 patients also showed abnormal LP. Of the 13 patients, 4 patients (31%) showed normal AP and survived. The remaining 9 patients (69%) showed abnormal AP and died. The mean values for AP were statistically different (p < 0.01) between survivor (0.72 +/- 0.16%) and nonsurvivor (1.52 +/- 0.40%) groups. Data from the normal volunteers and survival patients showed a 99mTc clearance slope < 1.00%. Data from patients who died showed a clearance slope > 1.00%. CONCLUSION: These results indicate that AP, measured by 99mTc DTPA aerosol inhalation lung scintigraphy, may help predict outcome in patients with paraquat intoxication.

Acute Disease↗
PubMed1998

Mast cells express novel CD8 molecules that selectively modulate mediator secretion.

CD8, a marker largely restricted to subsets of T lymphocytes and NK cells, was detected on freshly isolated rat peritoneal mast cells (PMC). Using flow cytometry, Percoll-enriched rat PMC (> or = 98% purity) were positive for the hinge region of CD8alpha (67.5 +/- 9.5%; Ab OX8) and CD8beta (27.8 +/- 2.3%; Ab 341). CD8+ PMC consisted of two populations, CD8alpha+ (22.5%) and CD8alpha+ beta+ (15.9%). Interestingly, G28, an Ab that identifies the IgV-like region of CD8alpha on T lymphocytes, did not bind PMC, suggesting that PMC CD8alpha is distinct from that on T lymphocytes. Moreover, a similar pattern of Ab positivity for CD8 was observed on a rat mast cell line, RBL 2H3. The presence of CD8alpha immunoreactivity on rat PMC was further confirmed by confocal microscopy. In situ reverse-transcription PCR and reverse-transcription PCR analysis demonstrated that PMC contained mRNA transcripts encoding CD8alpha. In functional studies of CD8 on PMC, both TNF-alpha and nitric oxide production were induced by OX8 (CD8alpha) and 341 Ab (CD8beta) in a dose-dependent manner. However, neither OX8 nor 341 induced histamine secretion from PMC. Ag-induced secretion of TNF-alpha, nitric oxide, and histamine was not affected by OX8 or 341 Abs, suggesting that there are distinct signaling mechanisms mediated by CD8 and Fc epsilonRI. These results indicate that rat PMC express functional CD8 molecules that may be distinct from those of T lymphocytes. The difference suggests there is a ligand other than MHC class I for mast cell CD8.

Animals↗
PubMed1998

Mechanisms of macrophage stimulation through CD8: macrophage CD8alpha and CD8beta induce nitric oxide production and associated killing of the parasite Leishmania major.

Prior studies demonstrated that rat macrophages express CD8, which differs from T lymphocyte CD8 within the ligand binding domain. We investigated whether stimulation of macrophage CD8 could induce mediator release and regulate host defense. Cross-linking either CD8alpha (OX8, 5 microg/ml) or CD8beta (341, 10 microg/ml) stimulated nitric oxide (NO) production, which correlated with an up-regulation of inducible NO synthase protein. Cell signaling inhibitors were used to elucidate the pathways of CD8alpha and CD8beta stimulation. Genistein (broad spectrum protein tyrosine kinase inhibitor, 10 microg/ml), PP1 (src family kinase inhibitor, 5 microg/ml), polymyxin B (protein kinase C (PKC) inhibitor, 100 microg/ml), and Ro 31-8220 (PKC inhibitor, 1 microM) significantly inhibited anti-CD8alpha- and anti-CD8beta-stimulated NO production and inducible NO synthase up-regulation, suggesting that tyrosine kinase(s) (src family) and PKC are involved in CD8 signaling. In addition, cross-linking CD8alpha stimulated NO-dependent macrophage killing of the parasite Leishmania major. For the first time, this work demonstrates that the beta-chain of macrophage CD8, in addition to the alpha-chain, can regulate mediator release. These results further illustrate the importance of this molecule and support our previous data demonstrating differences between macrophage and T lymphocyte CD8. Additional studies on the signaling mechanisms and possible ligand(s) for macrophage CD8 will lead to a greater understanding of inflammation and host defense.

Animals↗
PubMed1998

Effects of toxin A from Clostridium difficile on mast cell activation and survival.

Toxins A and B from Clostridium difficile are the main cause of antibiotic-associated diarrhea and pseudomembranous colitis. They cause fluid accumulation, necrosis, and a strong inflammatory response when inoculated in intestinal loops. Since mast cells are a rich source of inflammatory mediators, abundant in the gut, and known to be involved in C. difficile-induced enteritis, we studied the in vitro effect of toxin A on isolated mast cells. Normal rats sensitized by infection with Nippostrongilus brasiliensis were used to isolate peritoneal mast cells (PMC). PMC from naive rats were stimulated with calcium ionophore A23187 as a model of antigen-independent activation, and PMC from sensitized rats were stimulated with N. brasiliensis antigens to study immunoglobulin E-dependent mast cell activation. After 4 h, toxin A did not induce release of nitric oxide or histamine in naive PMC. However, 10 ng of toxin per ml caused a significant release of tumor necrosis factor alpha (TNF-alpha). In contrast, 1 microg of toxin per ml inhibited antigen or A23187-induced histamine release by PMC. Toxin A at 1 microg/ml for 4 h caused disruption of actin which aggregated in the cytoplasm and around the nucleus. After 24 h, chromatin condensation, cytoplasmic blebbing, and apoptotic-like vesicles were observed; DNA fragmentation was documented also. These results suggest that mast cells may participate in the initial inflammatory response to C. difficile infection by releasing TNF-alpha upon interaction with toxin A. However, longer exposure to toxin A affects the release of inflammatory mediators, perhaps because of the alteration of the cytoskeleton and induction of apoptosis. The impaired functions and survival of mast cells by C. difficile toxin A could hamper the capacity of these cells to counteract the infection, thus prolonging the pathogenic effects of C. difficile toxins.

Animals↗
PubMed1998

Unique cerebral dysfunction following triphenyltin acetate poisoning.

1. In animal studies, TPTA was found to be neurotoxic. In humans, variable CNS pictures have been described with or without significant EEG findings. Brain CT does not usually reveal any abnormalities. 2. Our patient presented with intermittent unique spontaneous involuntary movement of hands, facial twitching, silly smile and crying. Diplopia, drowsiness, giddiness, vertigo, bidirectional nystagmus, impairment of calculation ability, as well as disorientation to time, people and place also developed. EEG showed mild cortical dysfunction without seizures. MRI and Tc-99m HMPAO brain SPECT revealed no significant findings. TPTA may cause cellular dysfunction of brain without structural damage, which results in variable CNS clinical presentations. 3. Nadir of leucopenia was noted on the sixth day after consumption of TPTA. Liver impairment occurred on the ninth day. Borderline demyelinated neuropathy developed on the fifty-third day. CNS abnormalities, delayed peripheral neuropathy, hepatitis and leucopenia deserve monitoring for a prolonged period, even when the victim initially presents with GI upset only after consumption of TPTA.

Adult↗
PubMed1998

Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings.

Alocasia macrorrhiza (L) Schott and Endl is called Hai Yu, Tien Ho, Shan Yu, Kuan Yin Lien, Tu Chiao lien, Lao Hu Yu and Lang Du in Chinese. Its common English name is Giant Elephant's Ear. The toxic effects of A macrorrhiza arise from sapotoxin and include gastroenteritis and paralysis of the nerve centers. From 1985 to 1993 all individuals who called the Poison Control Center asking for information regarding macrorrhiza were included in this retrospective study. A questionnaire filled out by the Poison Control Center staff collected the demographic data of the victim, the reason for consumption, the prescribed part, clinical symptoms and signs of the victim, and medical outcome of poisonings. Among 27 cases of A macrorrhiza poisoning, the age was 1.5 to 68 y with 12 females and 15 males. One had skin contact and 1 had eye contact. In the 25 cases that consumed the plant leaf or tuber either raw or cooked, the primary symptom was in injected sore throat and the secondary symptom was numbness of the oral cavity. Some patients had salivation, dysphonia, abdominal pain, ulcers of the oral cavity, difficulty in swallowing, thoracodynia, chest tightness and swollen lips. We believe the presence of sapotoxin alone is not sufficient to explain the injected swollen and ulcerative lesions. Calcium oxalate is reported distributed in the entire plant and results in inflammation of the oral cavity and mucous membranes just as our patients had.

Adolescent↗
PubMed1997

Differential regulation of mast cell function by IL-10 and stem cell factor.

In the development of rodent mast cells (MC), IL-10 significantly enhances the growth factor activity of stem cell factor (SCF). The differential effects of IL-10 and SCF on function of rat peritoneal MC (PMC) are investigated in this study. IL-10 inhibits both constitutive and Ag-induced nitric oxide production by PMC in a dose-dependent manner, whereas SCF does not affect nitric oxide production by PMC. Short term (20-min) incubation with IL-10 does not affect Ag-induced histamine secretion, whereas long term (24-h) incubation with IL-10 significantly potentiates Ag-induced histamine secretion, an effect similar to those reported for IL-3 and IL-4 in mouse MC. By contrast, SCF significantly potentiates Ag-induced histamine secretion in both short term (20-min) and long term (24-h) experiments. Both constitutive and Ag-induced TNF-alpha production by PMC are dose-dependently inhibited by IL-10, whereas they are not affected by SCF at all doses tested (2-500 ng/ml) and incubation times observed (3-24 h). Interestingly, rat PMC constitutively express IL-10 mRNA and proteins, as tested by reverse transcription-PCR and immunocytochemistry. In addition, it was found by flow cytometry that 23.5% PMC express surface IL-10. Moreover, treatment of PMC with anti-IL-10 Ab for 6 h significantly potentiates constitutive and Ag-induced TNF-alpha production by rat PMC. Thus, IL-10 and SCF exert different regulatory effects on MC secretory function. IL-10 produced by MC has the potential to regulate MC function in an autocrine manner, an effect that may be highly relevant to responses involving MC activation.

Animals↗
PubMed1997

A novel CD8 molecule expressed by alveolar and peritoneal macrophages stimulates nitric oxide production.

Macrophages play an essential role in host defense, and we have identified a novel CD8 molecule, on alveolar and peritoneal macrophages, that may be involved in regulating this function. Flow cytometric analysis of bronchoalveolar lavage from normal rats identified a large number of CD8-positive cells that could not be accounted for by T lymphocytes. Within the scatter profile region in which the majority of cells were alveolar macrophages (OX41; 89 +/- 1%), 63 +/- 5% of the cells stained positively for CD8alpha (OX8) and 52 +/- 3% for CD8beta (341). Double-staining of lavage cells confirmed the presence of CD8 on alveolar macrophages. Interestingly, flow cytometry showed differences between CD8 on alveolar macrophages and on T lymphocytes within the ligand binding domain for MHC class I. Reverse transcription-PCR analysis on FACS-enriched alveolar macrophages showed the presence of CD8alpha mRNA, determining that macrophages synthesize CD8. Further studies identified both the alpha (49 +/- 8%)- and beta (37 +/- 4%)-chains of CD8 on peritoneal lavage cells (86 +/- 3% macrophages (OX42, CD11b)). As with alveolar macrophages, there were differences within the ligand-binding domain of CD8 on peritoneal macrophages compared with T lymphocytes. Functional studies determined that anti-CD8alpha (OX8) stimulated a dose-dependent release of nitric oxide, indicating that CD8 can directly regulate macrophage function. Thus, macrophages express an unusual CD8 molecule that differs within its ligand-binding domain, compared with T lymphocytes, and these findings suggest hitherto unknown ligand(s) for CD8. These findings will lead to a greater understanding of macrophage function and regulation.

Animals↗
PubMed1997

Traumatic brainstem deafness with normal brainstem auditory evoked potentials.

A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.

Auditory Pathways↗
PubMed1997

The difficulty in handling poisonings associated with Chinese traditional medicine: a poison control center experience for 1991-1993.

The purpose of this prospective case series was to outline the characteristics of Chinese traditional medicine poisonings and develop essential information for poison prevention and management. All phone inquiries made to the Poison Center related to Chinese traditional medicines from January 1, 1991 to December 31, 1993 were included. Standardized questionnaires were used to capture relevant information. Among the 318 phone inquiries about Chinese traditional medicines, 273 cases were classified as poisonings; and 22 mortalities occurred (6.9%). All of the poisonings occurred because of suicide attempts, accidents, or erroneous or improper use or processing. In our study, 47% of the potential toxic effects of Chinese traditional medicines were either unknown or could not be found in the literature. There existed undefinable uncertainty in attributing the clinical effects to the exposures to Chinese traditional medicines. We recommend that the strategy in handling Chinese traditional medicine poisonings to decrease mortality should be comprised of confirmation of the generic name of the substances and the specific part of the plant used, awareness of improper processing methods, maintenance of records on a broad review of systems and laboratory data, identification of active principles and potential interactions among the individual active agents; verification of histopathologic effects of the toxins; development of information on toxicodynamics and toxicokinetics; intensive supportive care for poisoned patients, and investigation of potential antidotes. There are several regulatory options available to health authorities to control the unrestricted use of these potentially toxic medicines and to help safeguard the public.

Adult↗
PubMed1996

Effects of salvianolic acid A on oxygen radicals released by rat neutrophils and on neutrophil function.

Salvianolic acid A (Sai A) has demonstrated potent antioxidant activity in previous studies. In the present study, the effects of Sai A on oxygen radicals released by rat neutrophils and on neutrophil function were investigated. Superoxide anion assayed by the nitroblue tetrazolium test and hydrogen peroxide detected with redox of scopoletin were scavenged concentration dependently by Sai A in n-formyl-methionyl-leucylphenylalanine (fMLP)- and phorbol myristate acetate (PMA)-stimulated rat neutrophils. Hydroxyl radicals generated in PMA-stimulated neutrophils, measured by HPLC, also were scavenged significantly by Sai A, whereas Sai A showed no significant effects on chemotaxis toward fMLP and phagocytosis of latex beads by rat neutrophils. In addition, the intracellular free calcium and cyclic nucleotide levels of neutrophils, when stimulated by fMLP, were not affected by Sai A. These results suggest that Sai A could significantly scavenge oxygen radicals released by activated neutrophils without affecting their functional ability.

Animals↗