Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 271 records · Page 15Linked to original sources

PubMed1996

Compound 48/80-induced conjunctivitis in the mouse: kinetics, susceptibility, and mechanism.

A mouse model of conjunctivitis has been developed by topical application of compound 48/80 (C48/80), an agent that triggers mast cell degranulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/J mouse strains to C48/80 stimulation, and of a mutant strain with mast cell depletion (WBB6F1/J and its sham control). Conjunctivae were collected and examined histopathologically at 15 min and 1,6,24,48 and 72 h after topical C48/80 administration. Conjunctival inflammation developed in all strains, although the severity varied. The conjunctivitis was characterized clinically by irritation, discharge, erythema, and chemosis. Pathology showed conjunctival infiltration with neutrophils, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulation of mast cells and evacuation of goblet cells were also observed. Late-phase inflammatory reactions peaked 6-24 h after C48/80 administration and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conjunctival inflammatory response similar to allergen-induced conjunctivitis. The depletion of mast cells significantly reduced the inflammation. This model which consistently mimics the clinical signs and histopathological processes of allergic conjunctivitis in humans, is practical and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the allergic inflammatory cascade.

Animals↗

PubMed1996

Diagnostic yield and therapeutic impact of flexible bronchoscopy in lung transplant recipients.

BACKGROUND: Bronchoalveolar lavage and transbronchial biopsy are often used for definitive diagnosis of lung rejection and infection in lung transplant recipients. Although protected specimen brushing is of value in nosocomial bacterial pneumonia, its role in lung transplant recipients had not been widely reported. The aim of the study is to review the diagnostic yield and therapeutic impact of flexible bronchoscopy with the use of a combination of bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy in lung transplant recipients. METHODS: We reviewed flexible bronchoscopy data in 83 transplant recipients between February 1990 and March 1995. Only those with bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy were included in the analysis. There were 282 bronchoscopies performed for clinically suspected lung rejection or infection (clinical bronchoscopy) and 38 bronchoscopies for follow-up of a previously detected histologic abnormality (follow-up bronchoscopy). RESULTS: The total yields for rejection and infection for clinical and follow-up bronchoscopies were 67.4% and 58.9%, respectively. Acute rejection was detected with transbronchial biopsy in 26.2% and 34.2% of clinical and follow-up bronchoscopies, respectively. Cytomegalovirus pneumonitis was detected with transbronchial biopsy in 4.0% and 11.4% of clinical and follow-up bronchoscopies, respectively. Overall, bacteria was the most common cause of lower respiratory tract infection. When used together, protected specimen brushing and bronchoalveolar lavage were complementary techniques for detection of bacterial lower respiratory tract infection with a significantly higher proportion detected with protected specimen brushing ( > or = 10(3) colony forming units/ml) compared with bronchoalveolar lavage ( > or = 10(5) colony forming units/ml) (p < 0.001). Complications were hemorrhage (1.9%), pneumothorax (2.5%) and transient hypoxemia (10.5%). The results had an impact on management of rejection and infection in 57.8% of clinical and 39.5% of follow-up bronchoscopies. CONCLUSIONS: We conclude that bronchoscopy, with the use of a combination of bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy, is safe with a high diagnostic yield and therapeutic impact for treating lung transplant recipients.

Biopsy↗

PubMed1996

Anti-tumor necrosis factor alpha therapy suppresses the induction of experimental autoimmune uveoretinitis in mice by inhibiting antigen priming.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) serves as a model for several immune-mediated diseases that affect the eye in humans. Previous studies indicated that tumor necrosis factor alpha (TNF-alpha) has an important proinflammatory role in EAU and possibly in human uveitis. In this study, the authors investigated the effect of anti-TNF-alpha therapy on EAU in mice. METHODS: Experimental autoimmune uveoretinitis was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). The mice were treated with 100 or 300 microliters rabbit antiserum or polyclonal antibodies to human TNF-alpha. The treatment spanned either the afferent or the efferent stage of EAU (days -1, 1, 3, 5, 7, or days 8, 10, 12, 14, 16, respectively). Control animals were injected with preimmune rabbit serum at the corresponding times or were not treated. Three weeks after immunization, EAU was assessed by clinical evaluation and by histopathology. Immunologic responses were assessed by delayed-type hypersensitivity (DTH), lymphocyte proliferation to IRBP, and relative abundance of IRBP-primed splenocytes. RESULTS: The treatment with rabbit anti-TNF-alpha serum significantly ameliorated disease when given during the afferent stage but had no effect when given during the efferent stage of EAU. The effect on DTH, lymphocyte proliferation, and abundance of antigen-reactive cells roughly paralleled the effect on disease. CONCLUSIONS: Neutralization of systemic TNF ameliorates EAU. The effectiveness of afferent treatment in comparison to the treatment during the efferent stage, together with the reduced proliferation and the reduced abundance of IRBP-responsive cells, suggest that interference with afferent-acting processes such as antigen priming is important to achieve protection from EAU by anti-TNF treatment.

Animals↗

PubMed1996

Topical cyclosporine inhibits mast cell-mediated conjunctivitis.

PURPOSE: Allergic conjunctivitis is a common condition caused by a mast cell-mediated hypersensitivity reaction to immunoglobulin E-bound allergens. The purpose of this study was to investigate the effect of topical cyclosporine A on the development of mast cell-mediated conjunctivitis in mice. METHODS: Allergic conjunctivitis was induced in C57BL/6 mice by topical applications of compound 48/80, a mast cell degranulating agent. In two separate experiments, mice were treated with topical cyclosporine A (0.05%, 0.2%, or 0.4%), prednisolone acetate 1%, or phosphate-buffered saline. Twenty-four hours after compound 48/80 instillation, the number of neutrophils, eosinophils, lymphocytes, macrophages, and the number of preserved goblet cells and undegranulated mast cells in the conjunctiva were counted by a masked observer. RESULTS: In both experiments, treatment with all three doses of cyclosporine A resulted in a statistically significant reduction in the number of infiltrating neutrophils and eosinophils compared to saline-treated controls. There was no significant difference in the treatment effect of cyclosporine and prednisolone acetate. In addition, there was increased preservation of goblet cells in the cyclosporine A-treated animals. Immunohistochemical staining showed a reduction in infiltrating lymphocytes and a smaller reduction in infiltrating macrophages in animals treated with cyclosporine compared to saline-treated controls. CONCLUSIONS: Topical cyclosporine A was effective in inhibiting the development of mast cell-mediated allergic conjunctivitis in mice. This study suggests that topical cyclosporine A may be effective in treating allergic conjunctivitis in humans.

Administration, Topical↗

PubMed1995

Cyclooxygenase-2 inhibitors. Synthesis and pharmacological activities of 5-methanesulfonamido-1-indanone derivatives.

The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing non-steroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)-thio]-5-methanesulfonamido-1-indanone++ + (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted 6-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t1/2 in squirrel monkeys, and seems less ulcergenic than 2 in rats.

Animals↗

PubMed1995

Periocular inflammation in mice with experimental systemic lupus erythematosus. A new experimental blepharitis and its modulation.

Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human monoclonal anti-DNA Ab, bearing a major Id 16/6Id. Immunized mice initially produce Abs to 16/6Id, DNA and nuclear Ags, and subsequently develop various clinical manifestations including leukopenia and renal immune complex disease. MHC class I Ags play a critical role in the induction and progression of experimental SLE. The present study reports that ocular changes also occur in mice with experimental SLE. The ocular disease is characterized by bilateral subacute and chronic inflammation of the eyelids (blepharitis) with immune complex IgG deposition and hypertrophic meibomian glands. The severity of ocular changes was strain dependent: most severe in 129 mice, less intense in BALB/c animals and only minimal in C3H.SW mice. No blepharitis developed in mice deficient in MHC class I expression. Further, the disease was strongly inhibited in BALB/c mice treated with methimazole, an agent that has been shown to repress transcription of MHC class I. In these cases, there was no IgG deposition and a decreased infiltration of inflammatory cells in the eyelids. These observations thus suggest that, similar to the observation with experimental SLE, MHC class I is critical in the onset of this experimental autoimmune blepharitis. The new experimental eye disease described here provides an animal model for chronic blepharitis in humans, a common condition for which such a model has been sought.

Animals↗

PubMed1995

Synergistic effect of rapamycin and cyclosporin A in the treatment of experimental autoimmune uveoretinitis.

Immunosuppressive drugs currently available for the treatment of autoimmune diseases display a narrow therapeutic window between efficacy and toxic side effects. The use of combinations of drugs that have a synergistic effect may expand this window and reduce the risk of toxicity. We evaluated the combination effect of rapamycin (Rapa) and cyclosporin A (CsA) in an autoimmune disease model of the eye. The dose-effect relationship of Rapa with CsA was measured in vitro on the inhibition of proliferation of retinal S-Ag-primed lymphocytes. A median effect analysis was performed and a combination index (CI) calculated for 50% inhibition of proliferation. Rapa and CsA were markedly synergistic over a wide dose range (lowest CI = 0.31). Calculated dose reduction factors indicated that Rapa could be reduced nine-fold and CsA reduced five-fold when these drugs were used in combination. These reduced doses were tested in vivo for the treatment of experimental autoimmune uveoretinitis (EAU). Twelve of 15 rats treated with CsA, 2 mg/kg/day, developed EAU with a median severity of 2.5. Fourteen of 15 rats treated with Rapa, 0.01 mg/kg/day, developed EAU with a median severity of 3.25. Complete inhibition of EAU was achieved in all 15 animals treated with the combination of Rapa and CsA (combined vs CsA alone, p < 0.0002; combined vs Rapa alone, p < 0.00001). The demonstrated synergistic relationship between Rapa and CsA will allow the use of reduced doses of each drug to achieve a therapeutic effect. The use of lower doses may reduce the toxicity of these drugs for the treatment of autoimmune uveitis.

Animals↗

PubMed1995

32 cases of sympathetic ophthalmia. A retrospective study at the National Eye Institute, Bethesda, Md., from 1982 to 1992.

OBJECTIVE: To examine the relationship between visual outcome and the clinical management of patients with sympathetic ophthalmia. METHODS: Thirty-two patients with sympathetic ophthalmia who were seen at the National Eye Institute, Bethesda, Md, between 1982 and 1992, were retrospectively reviewed. RESULTS: There were equal numbers of males and females. Sympathetic ophthalmia occurred after trauma in 23 patients and surgery in nine patients. Sixteen of the 32 patients had a final visual acuity of 20/40 or better; 10 patients had a visual acuity worse than 20/200. Good visual outcome was associated with early and aggressive treatment with corticosteroids, sometimes in combination with other immunosuppressive agents. Poor visual acuity was associated with glaucoma, chorioretinal scars in the macula, and persistent uncontrolled inflammation. CONCLUSION: Prompt and aggressive use of antiinflammatory therapy can improve the visual outcome of patients with sympathetic ophthalmia.

Adolescent↗

PubMed1995

Selective inhibitors of COX-2.

The main target of non-steroidal anti-inflammatory drugs (NSAIDs) is prostaglandin G/H synthase (PGHS), also known as cyclooxygenase (COX), which exists as two isoforms. In order to evaluate the contributions of PGHS isoforms to physiological and pathological conditions and their sensitivity to inhibition by non-steroidal anti-inflammatory drugs, we have established high level expression systems of recombinant human PGHS isoforms. The inducible form of PGHS, termed PGHS-2, has been purified and characterized with respect to substrate specificity, product formation, enzymatic activity, glycosylation, heme content, quaternary structure, and modification by aspirin. Pharmacological profiles of the recombinant PGHS isoforms indicate that conventional NSAIDs show little selectivity for either enzyme, however, the recently described NSAID, NS-398, exhibits a high degree of specificity for PGHS-2 through a time dependent mechanism.

Animals↗

PubMed1995

Interleukin-10 in the vitreous of patients with primary intraocular lymphoma.

PURPOSE: To find an accurate and simple method to diagnose primary intraocular lymphoma. METHODS: We prospectively analyzed concentrations of interleukin-10, interleukin-1, interleukin-2, interleukin-4, and interleukin-6 in vitrectomy specimens from three patients with primary intraocular lymphoma and five patients with uveitis by enzyme-linked immunosorbent assay. RESULTS: Interleukin-10 in the vitreous was detected in patients with primary intraocular lymphoma. Interleukin-10 levels correlated with clinical activity and the number of malignant cells. CONCLUSION: Concentrations of interleukin-10 in the vitreous may be a helpful clue to both clinicians and pathologists in diagnosing primary intraocular lymphoma.

Enzyme-Linked Immunosorbent Assay↗

PubMed1995

Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis.

We studied the effect of monoclonal antibodies (mAbs) against CD54 (intercellular adhesion molecule-1; ICAM-1) and CD11a (lymphocyte function-associated antigen-1; LFA-1) on the prevention and treatment of endotoxin-induced uveitis (EIU). When treated at the time of endotoxin injection the mean number of inflammatory cells infiltrating the eye +/- S.E.M. on histologic sections was 469.2 +/- 51.9 for controls, 13.8 +/- 2.6 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 195.8 +/- 48.8 for rats receiving anti-LFA-1 mAb (P = 0.0003). When treated after the start of inflammatory disease, the mean number of infiltrating inflammatory cells +/- S.E.M. was 273.0 +/- 30.7 for controls, 6.4 +/- 1.7 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 54.2 +/- 7.6 for rats receiving anti-LFA-1 mAb (P < 0.0001). The mean number of cells per milliliter of aqueous humor +/- S.E.M. was 1867.6 +/- 321.8 for controls, 21.7 +/- 5.3 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 295.1 +/- 71.2 for rats receiving anti-LFA-1 mAb (P < 0.0001). MAbs against ICAM-1 and LFA-1 significantly inhibited the development of EIU and were effective in treating clinically evident ocular inflammatory disease.

Animals↗

PubMed1995

Endotoxin induced uveitis in the mouse: susceptibility and genetic control.

Endotoxin induced uveitis in the mouse provides a useful animal model for acute anterior uveitis in humans. We have investigated the susceptibility of endotoxin-induced uveitis among various mouse strains, and have examined the relationship between genetic background and the resultant inflammatory response to endotoxin. We studied ten strains with differing major histocompatibility-2 genes, lipopolysaccharide response gene, and strains with mast cell depletion and its sham control. Anterior uveitis was induced by injecting 300 micrograms of Salmonella typhimurium endotoxin into one hind footpad. Mice were then killed 8, 12, 16, 20, 24, 48 and 72 hr after endotoxin injection, and vertical sections of the eyes through the pupil-optic nerve axis were evaluated for ocular inflammation. C3H/HeN mice developed severe uveitis. In contrast, C3H/HeJ mice (lipopolysaccharide response gene-) did not develop uveitis even though it has the same genetic background and shares the same major histocompatibility-2 haplotype with C3H/HeN mice (lipopolysaccharide response gene+). The strain that was mast-cell deficient (W/Wv) developed minimal uveitis; however, W/+ mice, with mast cells, developed more inflammation at 48 and 72 hr after endotoxin injection. C3H.SW and FVB/N mice also developed severe uveitis, and BALB/C, CBA/J, and B10.A developed mild uveitis. In conclusion, there is a wide variation in the magnitude and susceptibility to endotoxin among mouse strains. Multiple factors appear to influence this variability, including non-histocompatibility-2 genetic background, the lipopolysaccharide response gene, and the presence of mast cells.

Animals↗

PubMed1995

Side effects of rapamycin in the rat.

The side effects of Rapamycin was evaluated by histopathological examination of the heart, kidneys, and eyes of treated Lewis rats. Rapamycin was administered during 14 days by continuous intravenous infusions at doses of 0.5, 1.0, and 1.5 mg/kg/day. Focal myocardial infarction was observed in three of five rats with Rapamycin given at 1.5 mg/kg/day and two of 22 rats with 1.0 mg/kg/day. There were no sign of myocardial toxicity at a Rapamycin dose of 0.5 mg/kg/day. The retina of one eye of a rat treated at a dose of 1.5 mg/kg/day had a small area of focal ischemic necrosis. The kidneys were normal at all doses.

Animals↗

PubMed1995

Involvement of NK1 and NK2 receptors in pulmonary responses elicited by non-adrenergic, non-cholinergic vagal stimulation in guinea-pigs.

Previous studies from our laboratory using exogenously administered neurokinin (NK) agonists have shown that both NK1- and NK2-receptor subtypes are involved in plasma extravasation in the guinea-pig airways. In the present study, we have extended these observations using antidromic vagal stimulation to stimulate sensory c-fibres as a means of eliciting the release of endogenous tachykinins in propranolol- and atropine-treated guinea-pigs. Antidromic vagal stimulation (5 ms, 30 s) induced frequency-dependent (1-10 Hz) bronchoconstriction that was completely abolished by co-administration of the NK1-selective antagonist CP-99,994 ((2s-methoxy-benzyl)-(2-phenyl-piperidin-3s-yl)-amine), and the NK2-selective antagonist SR-48,968 ((S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl) butyl]benzamide), each at a dose sufficient to block NK1 and NK2 receptors, respectively (each at 0.3 mg kg-1, i.v.). In contrast, SR-48,968 when given alone only partially blocked the vagal stimulation-induced bronchospasm, whereas CP-99,994 had no effect. Significant increases (2-3-fold) in plasma extravasation of [125I]fibrinogen in the trachea, main bronchi, distal airways and oesophagus following vagal stimulation (5 Hz, 5 min, 10 V, 5 ms) were observed. Pretreatment with the neutral endopeptidase inhibitor, thiorphan (1 mg kg-1, i.v.), and the angiotensin-converting enzyme inhibitor, enalapril (1 mg kg-1, i.v.), potentiated both vagal stimulation-induced bronchoconstriction and plasma leakage in all tissues examined. This potentiation was due to reduced metabolism of endogenously released tachykinins since enhanced plasma overflow of immunoreactive substance P was observed following vagal stimulation in thiorphan- and enalapril-treated guinea-pigs. CP-99,994 substantially blocked plasma leakage in all parts of the airways and in the oesophagus. In comparison, SR-48,968 had no significant effect in the trachea and the oesophagus but partially inhibited plasma leakage in the main bronchi and distal airways. Co-administration of both CP-99,994 and SR-48,968 abolished the residual plasma leakage in these two regions. These results support the hypothesis that both NK1 and NK2 receptors are involved in tachykinin-induced pulmonary responses in the airways.

Animals↗

PubMed1995

Neurokinin receptors subserving plasma extravasation in guinea pig airways.

In the respiratory system the tachykinins substance P and neurokinin A exhibit a variety of effects on airway function that include bronchoconstriction, vasodilatation, and plasma extravasation. Increased microvascular permeability with accompanying plasma extravasation is a principal cause of tissue edema observed in asthma. In guinea pig airways it has been suggested that neurogenic plasma extravasation is mediated by tachykinins, released from sensory nerve terminals, acting via neurokinin (NK) receptors. We have characterized NK receptor mediated plasma extravasation in guinea pig airways, using 125I-labelled human fibrinogen as a marker for leakage. Extravasation was induced using selective NK1 and NK2 receptor agonists, capsaicin, or nonadrenergic, noncholinergic nerve stimulation. The inhibitory effects of the selective nonpeptide NK receptor antagonists (CP 99,994 for NI1 and SR 48,968 for NK2) were also examined. Results from our studies demonstrate conclusively that only NK1 receptors subserve plasma extravasation in the trachea and large airways of the guinea pig. In start contrast, extravasation in the lower airways (secondary bronchi and intraparenchymal airways) of the guinea pig is mediated by both NK1 and NK2 receptors.

Animals↗

PubMed1995

Effect of dexamethasone on antigen-induced high molecular weight glycoconjugate secretion in allergic guinea pigs.

The ovalbumin-sensitized guinea pig is commonly used as a small animal model of allergic asthma. This animal model exhibits many of the hallmark characteristics observed in patients afflicted with asthma including nonspecific airway hyperreactivity, airway eosinophilia, early and late phase bronchoconstriction, and plasma extravasation into the airways. In addition, mucous hypersecretion in the airways of asthmatic patients is thought to be responsible for the plugging of distal airways and to contribute to the morbidity and mortality associated with the disease process. In this study we examined whether the allergic guinea pig model exhibits an increase in airway high molecular weight glycoconjugate (HMWG) secretion in response to an antigen challenge and whether dexamethasone exerts any modulatory effects upon the response. Ovalbumin (OVA) -sensitized guinea pigs were challenged with OVA 2 wk following the initial exposure. Trachobronchoalveolar lavages (TBAL) were performed, and the samples were assayed for total eosinophil cell number, eosinophil peroxidase activity (EPO), and both acidic and neutral HMWG content. Morphometric analysis of mucous-containing cells was also performed on tissue sections prepared from the trachea, mainstem bronchus, and three lobes of the left lung. Within 24 h of an antigen challenge, TBAL samples obtained from the allergic guinea pigs exhibited increases in eosinophil cell number, measured EPO enzyme activity, and acidic HMWG content compared to TBAL samples prepared from vehicle-exposed animals. These antigen-induced changes were dependent on the concentration of aerosolized OVA administered. Exposing the animals to 0.3% OVA provoked a 6.23-fold increase in airway eosinophils, 15-fold elevation in TBAL EPO enzyme activity, and 175% increase in TBAL acidic HMWG. No significant changes in TBAL neutral HMWG were measured. The changes in measured EPO activity correlated with the levels of acidic HMWG found in the TBAL samples (r = 0.73, P < or = 0.001). The measured increase in TBAL acidic HMWG was time dependent and was found to be maximal at 2 h post-antigen challenge. Morphometric analysis of Alcian blue (pH 2.5) -stained airway sections showed a decline in stored mucosubstances following the antigen exposure, supporting the notion that the allergic guinea pig model exhibits a mucosecretory component. Pretreating the animals with dexamethasone attenuated the antigen-induced release of HMWG and changes in measured EPO activity. In conclusion, these data indicate that the allergic guinea pig may be a useful model for examining the neural and cellular mechanisms underlying mucus hypersecretion in individuals afflicted with bronchial asthma.

Animals↗

PubMed1995

Lung elastic recoil in normal young adult Chinese compared with Caucasians.

Chinese people have smaller total lung capacity (TLC) compared with Caucasians of similar age, sex and height. One possible reason would be a higher lung elastic recoil in Chinese. Most published values for lung elastic recoil viz static lung compliance (CLst), shape constant K, and maximal static transpulmonary pressure (PLmax) have been from Caucasian subjects. The aim of our study was to obtain values for lung elastic recoil in normal young adult Chinese subjects. Static expiratory pressure-volume (P-V) curves were studied in 22 healthy Chinese subjects (12 males and 10 females). The P-V curve was fitted using an iterative least mean squares regression on a computer, according to an exponential equation: V = A-Be-KP, where V is lung volume, P is transpulmonary pressure, and A, B and K are constants. Mean values +/- SD for K, CLst and PLmax were 0.12 +/- 0.04, 230 +/- 103 ml.cmH2O-1 and 27.5 +/- 7.5 cmH2O, respectively. The values of CLst and K were similar to that of normal Caucasian subjects, whereas values of PLmax were lower. We attributed the lower PLmax partly to weaker inspiratory muscles in Chinese compared with Caucasians. We conclude that lung elastic recoil in normal young adult Chinese is similar to that of healthy young adult Caucasians. Hence, lung elasticity is unlikely to explain the racial differences in static lung volumes.

Adult↗

PubMed1995

Immune corticotropin-releasing hormone is present in the eyes of and promotes experimental autoimmune uveoretinitis in rodents.

We examined the presence and potential role of local corticotropin-releasing hormone (CRH) in experimental uveitis in rodents. This 41-amino acid peptide, originally isolated from the hypothalamus, is also secreted locally in experimentally induced and natural inflammatory sites, where it exerts autocrine or paracrine proinflammatory effects. Female Lewis rats were immunized with the major pathogenic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein in complete Freund's adjuvant, monitored daily, and killed 8, 9, 10, 12, 14, or 18 days later, after having developed uveoretinitis. Immunoreactive CRH (IrCRH) was detected by immunohistochemistry in the uveitic eyes in the cytoplasm of inflammatory cells (macrophages, lymphocytes, and polymorphonuclear cells) infiltrating the iris, ciliary body, vitreous, retina, and choroid depending on the stage of the disease. The intensity of the IrCRH staining was positively correlated with the severity of the disease based on morphological criteria. The amount of IrCRH measured by RIA varied between 0.18 +/- 0.03 (mean +/- SE) and 0.79 +/- 0.07 pmol/g wet tissue (8th and 14th day of the disease, respectively). Ophthalmic IrCRH in uveitic rat eyes had similar chromatographic mobility as rat/human CRH-(1-41) by HPLC. Furthermore, female B10.A mice were immunized with interphotoreceptor retinoid-binding protein and treated during the induction (0-7 days) or expression (8-16 days) stages of the disease with ip injections of the anti-CRH antibody TS-2 or placebo nonimmune rabbit serum. The early anti-CRH treatment significantly decreased the disease intensity compared to that in placebo- or late-treated animals (P < 0.05, by analysis of variance). We conclude that IrCRH is present at the site of inflammation in rodent experimental uveitis and that its expression correlates with the natural history and intensity of the disease. Immune CRH appears to play an early pathogenetic role in the induction of experimental uveitis.

Animals↗