Biomedical subjects

Y Chang

Publications and source records attributed to Y Chang.

At least 91 records · Page 5Linked to original sources

PubMed2000

Borderline tumors of the ovary: correlation of frozen and permanent histopathologic diagnosis.

OBJECTIVE: To evaluate the correlation between the diagnosis of borderline tumor of the ovary by frozen and permanent pathology. METHODS: All pathology reports with diagnoses of borderline tumor of the ovary between 1980 and 1998 at Massachusetts General Hospital were reviewed. Univariate and multivariable logistic regression models were constructed for patient age, tumor size, histology, presence of bilateral or extraovarian disease, and concurrent diagnosis of endometriosis or endosalpingiosis. RESULTS: We reviewed 140 cases. The average age of patients was 52.3 years. Eighty tumors were serous, 47 mucinous, 11 mixed, and two endometrioid. The mean diameter overall was 13.7 cm (range 1-70 cm), 10.2 cm for serous, and 20.1 cm for mucinous. Diagnoses of borderline tumors by frozen and permanent pathology were consistent in 60% of cases. Frozen section interpreted a benign lesion as malignant (overdiagnosed) in 10.7% of cases, and interpreted a malignant lesion as benign (underdiagnosed) in 29.3%. No variable was a significant predicator of overdiagnosis. In univariate analysis, underdiagnosis was more likely for other types of tumors than serous (P <.001), tumors larger than 20 cm (P =.039), and tumors confined to the ovaries (P =. 009). When all variables were included in a multiple regression model, only histology was a significant predictor of underdiagnosis (P =.039). CONCLUSION: Frozen or permanent pathology reports of diagnoses of borderline tumor were consistent 60% of the time, whereas the positive predictive value of borderline by frozen section was 89.3%. Tumors other than serous are more likely to be misinterpreted.

Adenocarcinoma↗

PubMed2000

Health status in allergic rhinitis.

Although valid and reliable instruments exist to measure the quality of life of allergic rhinitis patients, a statistically sensitive and clinically meaningful way to evaluate patients undergoing immunotherapy has not been reported. A 21-site prospective, observational study was performed in a population of consecutive patients with allergic rhinitis. Baseline general health measures revealed significant (P < 0.05) decrements from reported normative levels in 8 domains for patients choosing to undergo immunotherapy and 5 domains for patients choosing not to undergo immunotherapy. The General Health Survey was less sensitive in detecting change than the Nasal Health Survey (Chronic Sinusitis Survey) and allergy-specific (Rhinoconjunctivitis Quality of Life Questionnaire and Allergy Outcome Survey) surveys. Severity of symptoms was associated with both the likelihood to choose immunotherapy and the likelihood for early improvement. We conclude that general and condition-specific measures can be used to observe patients after immunotherapy; however, obtaining baseline data and controlling for seasonality are important considerations.

Adolescent↗

PubMed2000

Outcomes of septoplasty.

A prospective nonrandomized study of consecutive patients presenting to the Massachusetts Eye and Ear Infirmary for septoplasty was conducted to evaluate patient-based outcome. Patients received statistically validated measures of general health status (Short Form-12) and nasal specific health (Nasal Health Survey) before and 6 and 12 months after surgery. Multiple perioperative patient- and surgeon-dependent treatment variables were also evaluated to determine the impact on outcome. A total of 161 patients were entered into the study, and 93 were available for statistical analysis. At 9 months the mean follow-up (range 6-12 months), both symptom and medication subscores of the Nasal Health Survey, and the total score demonstrated significant improvement (P < 0.05); 71% of patients had clinically significant improvement as determined by at least a 50% decrease in duration of nasal symptoms. Measures of general health did not differ significantly from normative values at baseline and did not change after surgical intervention. Predictor analysis revealed that female gender and a history of previous nasal surgery predicted worse outcome.

Adult↗

PubMed2000

Regulation of T-helper-1 versus T-helper-2 activity and enhancement of tumor immunity by combined DNA-based vaccination and nonviral cytokine gene transfer.

Intramuscular (i.m.) injections of a plasmid encoding human carcinoembryonic antigen (CEA) elicited both humoral and cellular immune responses in mice, but only partial inhibition of the growth of transplanted syngeneic CEA-positive P815 tumor cells (CEA/P815). Coinjection of the CEA vector with a vector encoding either interferon-gamma (IFN gamma) or IL-12 promoted IgG2a isotype anti-CEA antibody production, anti-CEA/P815 CTL activity and greater resistance to CEA/P815 tumor challenge. As well, CEA/P815-stimulated IFN gamma secretion in vitro was increased, but IL-4 diminished, consistent with a T-helper type 1 (Th1) response. In contrast, coinjection of the CEA vector with an IL-4 vector increased IgG1 production, but reduced CTL activity and resistance to tumor challenge. The latter treatment inhibited CEA/P815-dependent IFN gamma production but enhanced IL-4 secretion, consistent with a Th type 2 (Th2) response. Antitumor immunity was enhanced when the CEA and IL-12 plasmids were coinjected at the same muscle site, but not at separate sites despite increased serum IL-12 levels. Though the tumor cells expressed neomycin phosphotransferase, mice immunized with vectors encoding that protein (without CEA) were not protected against tumor growth, and produced no CTLs except for low levels when coinjected with an IL-12 vector. Thus, we show that immunity elicited by DNA vaccination against CEA can be biased to a protective type (high Th1 and CTL activity) or nonprotective type (high Th2 and low CTL activity) by i.m. coinjection of cytokine-expressing plasmids. IL-12 appears to act locally, but not systemically, through an adjuvant effect.

Analysis of Variance↗

PubMed2000

IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice.

Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA humoral, T-helper-1 and cytotoxic T lymphocyte (CTL) responses, and resistance to a CEA/LLC tumor challenge such that 80% of mice remained tumor free. Injection of the IL- 12 plasmid alone was not protective. To analyze immune requirements, we immunized gene knockout (KO) mice of C57BL/6 background, deficient in either CD3, CD4, CD8, interferon gamma (IFNgamma), perforin or Fas ligand (FasL). Only CD3+ mice expressing both CD4 and CD8, which appear equally important, as well as IFNgamma and perforin, could fully resist a tumor challenge. IL-12 stimulated CTL activity, which was strictly CD3/CD8/perforin-dependent. FasL-KO mice had normal CTL activity and tumor resistance, indicating that only the perforin lytic pathway was involved. CD4-KO and IFNgamma-KO mice still generated CTLs. CEA-stimulated IFNgamma production occurred in both CD4- or CD8-KO mice and in both cases was augmented by IL-12. In IFNgamma-KO mice, IL-12 still enhanced anti-CEA antibody production but only moderately restored impaired DTH and tumor resistance. We conclude that the immune requirements for tumor rejection are stringent, involving multiple mechanisms which are all enhanced by IL-12.

Animals↗

PubMed2000

Topical ALA-photodynamic therapy for the treatment of acne vulgaris.

Topical aminolevulinic acid is converted into a potent photosensitizer, protoporphyrin, in human hair follicles and sebaceous glands. Photodynamic therapy with topical aminolevulinic acid was tested for the treatment of acne vulgaris, in an open-label prospective human study. Each of 22 subjects with acne on the back was treated in four sites with aminolevulinic acid plus red light, aminolevulinic acid alone, light alone, and untreated control. Half of the subjects were treated once; half were treated four times. Twenty percent topical aminolevulinic acid was applied with 3 h occlusion, and 150 J per cm2 broad-band light (550-700 nm) was given. Sebum excretion rate and auto-fluorescence from follicular bacteria were measured before, and 2, 3, 10, and 20 wk after, treatment. Histologic changes and protoporphyrin synthesis in pilosebaceous units were observed from skin biopsies. Aminolevulinic acid plus red light caused a transient acne-like folliculitis. Sebum excretion was eliminated for several weeks, and decreased for 20 wk after photodynamic therapy; multiple treatments caused greater suppression of sebum. Bacterial porphyrin fluorescence was also suppressed by photodynamic therapy. On histology, sebaceous glands showed acute damage and were smaller 20 wk after photodynamic therapy. There was clinical and statistically significant clearance of inflammatory acne by aminolevulinic acid plus red light, for at least 20 wk after multiple treatments and 10 wk after a single treatment. Transient hyperpigmentation, superficial exfoliation, and crusting were observed, which cleared without scarring. Topical aminolevulinic acid plus red light is an effective treatment of acne vulgaris, associated with significant side-effects. Aminolevulinic acid plus red light causes phototoxicity to sebaceous follicles, prolonged suppression of sebaceous gland function, and apparent decrease in follicular bacteria after photodynamic therapy. Potentially, aminolevulinic acid plus red light may be useful for some patients with acne.

Acne Vulgaris↗

PubMed2000

Factors influencing the long-term outcome of mandibular reconstruction.

PURPOSE: The aim of this study was to understand the association of 30 candidate variables with the outcome of mandibular reconstruction. PATIENTS AND METHODS: Seventy cases of mandibular reconstruction performed between 1976 and 1991 were identified. Medical records were reviewed for all patients. Thirty variables, including patient factors, preoperative preparation, and intraoperative and postoperative findings were determined for each patient. Bone graft outcome was evaluated in 2 ways: 1) Fisher's exact tests and logistic regression models were used to determine the association between the clinical parameters and the success of the bone graft at 1 year and 2) proportional hazard regression models were then used to identify the predictors of bone graft survival time from the 30 chosen variables. RESULTS: Multivariate analysis determined that greater blood loss during the procedure (P = .018) and the presence of postoperative recipient site complications (P = .010) were significantly associated with bone graft failure during the first year. The diagnosis of malignant disease (P = .006), the use of sternocleidomastoid muscle (SCM) flaps for soft tissue augmentation (P < .001), longer duration of suction drainage (P = .001), and the presence of postoperative recipient site complications (P = .013) were found to be significant predictors of graft survival time in the proportional hazard regression model. CONCLUSIONS: The analysis of parameters associated with bone graft outcome may aid in surgical decision making and help improve the likelihood of a successful result in the future.

Adolescent↗

PubMed2000

Epidural cooling for spinal cord protection during thoracoabdominal aneurysm repair: A five-year experience.

PURPOSE: We developed and applied a method for providing regional spinal cord hypothermia with epidural cooling (EC) during thoracoabdominal aneurysm (TAA) repair. Preliminary results indicated significant reduction in spinal cord ischemic complications (SCI), compared with historical controls, and a 5-year experience with EC was reviewed. METHODS: From July 1993 to September 1998, 170 patients with thoracic aneurysms (n = 14; 8.2%) or TAAs (types I and II, n = 83 [49%]; type III, n = 66 [39%]; type IV, n = 7 [4.1%]) were treated with EC. An earlier aneurysm resection was noted in 44% of patients, an emergent operation was noted in 20% of patients, and an aortic dissection was noted in 16% of patients. The EC was successful (mean cerebrospinal fluid [CSF] temperature at cross-clamp, 26.4 +/- 3 degrees C) in 97% of cases, with all 170 patients included in an intention-to-treat analysis. The operation was performed with a clamp/sew technique (98% patients) and selective (T(9) to L(1) region) reimplantation of intercostal vessels. Clinical and EC variables were examined for association with operative mortality and SCI by means of the Fischer exact test, and those variables with a P value less than.1 were included in multivariate logistic regression analysis. RESULTS: The operative mortality rate was 9.5% and was weakly associated (P =.07) with SCI; postoperative cardiac complications (odds ratio [OR], 35. 3; 95% CI, 5.3 to 233; P <.001) and renal failure (OR, 32.2; 95% CI, 6.6 to 157; P <.001) were the only independent predictors of postoperative death. SCI of any severity occurred in 7% of cases (type I/II, 10 of 83 [12%]; all other types, 2 of 87 [2.3%]), versus a predicted (Acher model) incidence of 18.5% for this cohort (P =. 003). Half the deficits were minor, with good functional recovery, and devastating paraplegia occurred in three patients (2.0%). Independent correlates of SCI included types I and II TAA (OR, 8.0; 95% CI, 1.4 to 46.3; P =.021), nonelective operation (OR, 8.3, 95% CI, 1.8 to 37.7; P =.006), oversewn T(9) to L(2) intercostal vessels (OR, 6.1; 95% CI, 1.3 to 28.8; P =.023), and postoperative renal failure (OR, 23.6; 95% CI, 4.4 to 126; P <.001). These same clinical variables of nonelective operations (OR, 7.7; 95% CI, 1.4 to 41.4; P =.017), oversewn T(9) to L(2) intercostal arteries (OR, 9.7; 95% CI, 1.5 to 61.2; P =.016), and postoperative renal failure (OR, 20.8; 95% CI, 3.0 to 142.1; P =.002) were independent predictors of SCI in the subgroup analysis of high-risk patients, ie, patients with type I/II TAA. CONCLUSION: EC has been effective in reducing immediate, devastating, total paraplegia after TAA repair. A strategy that combines the neuroprotective effect of regional cord hypothermia, avoiding the sacrifice of potential spinal cord blood supply, and postoperative adjuncts (eg, avoidance of hypotension, CSF drainage) appears necessary to minimize SCI after TAA repair.

Adolescent↗

PubMed2000

Neuromuscular effects of mivacurium in 2- to 12-yr-old children with burn injury.

BACKGROUND: Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium. METHODS: Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at < or = 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion. RESULTS: The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn. CONCLUSIONS: A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. diatrics; plasma cholinesterase; relaxant resistance; succinylcholine, alternative to.)

Body Weight↗

PubMed2000

Outcome of pancreaticoduodenectomy with pylorus preservation or with antrectomy in the treatment of chronic pancreatitis.

OBJECTIVE: To compare the short- and long-term results of pancreaticoduodenectomy with pylorus preservation (PPPD) or with antrectomy (Whipple procedure) in the treatment of selected patients with chronic pancreatitis. BACKGROUND: PPPD may be preferred over Whipple because of its purported nutritional advantages and the reduced likelihood of postgastrectomy syndromes. METHODS: A retrospective review was performed of 72 consecutive patients undergoing pancreaticoduodenectomy for chronic pancreatitis between 1991 and 1997. RESULTS: PPPD was performed in 39 patients and Whipple in 33. The two patient populations had similar characteristics. Short-term complications included (PPPD vs. Whipple): pancreatic or biliary fistulas (5.1% vs. 15%), delayed gastric emptying (33% vs. 12%), cholangitis (2.6% vs. 6.1%), and death (0 vs. 3%). Delayed gastric emptying was not associated with other complications and resulted in longer hospital stays for PPPD than for Whipple patients (15 vs. 12 days). The duration of follow-up averaged 41 +/- 24 months. Long-term weight status was similar, with body-mass indices of 22.1 and 22.9 after PPPD and Whipple, respectively. Postoperative enzyme supplementation (63% vs. 77%) and new-onset diabetes (10% vs. 12%) did not differ significantly between the PPPD and Whipple groups. Dumping, bile gastritis, or peptic ulcer disease occurred in three patients after PPPD and in three after Whipple. Complete or partial pain relief was attained in 60% and 70% of patients after PPPD and Whipple, respectively. Multivariate analysis of preoperative variables revealed that site-specific pathology in the head of the pancreas was the only independent factor associated with successful pain relief after pancreatic resection. CONCLUSION: PPPD results in higher frequencies of postoperative delayed gastric emptying compared with the Whipple procedure. Both operations achieve comparable long-term nutritional results, cause new insulin dependence in surprisingly few patients, and provide equivalent pain relief to 65% of selected patients. Patients with disproportionate pathology in the head of the pancreas have a higher likelihood of successful pain relief.

Adult↗

PubMed2000

Velocity space scattering coefficients with applications in antihydrogen recombination studies

An approach for calculating velocity space friction and diffusion coefficients with Maxwellian field particles is developed based on a kernel function derived in a previous paper [Y. Chang and C. A. Ordonez, Phys. Plasmas 6, 2947 (1999)]. The original fivefold integral expressions for the coefficients are reduced to onefold integrals, which can be used for any value of the Coulomb logarithm. The onefold integrals can be further reduced to standard analytical expressions by using a weak coupling approximation. The integral expression for the friction coefficient is used to predict a time scale that describes the rate at which a reflecting antiproton beam slows down within a positron plasma, while both species are simultaneously confined by a nested Penning trap. The time scale is used to consider the possibility of achieving antihydrogen recombination within the trap. The friction and diffusion coefficients are then used to derive an expression for calculating the energy transfer rate between antiprotons and positrons. The expression is employed to illustrate achieving antihydrogen recombination while taking into account positron heating by the antiprotons. The effect of the presence of an electric field on recombination is discussed.

Journal Article↗

PubMed2000

A unique 33-kD cysteine proteinase accumulates in response to larval feeding in maize genotypes resistant to fall armyworm and other Lepidoptera.

Plants respond to insect feeding with a number of defense mechanisms. Using maize genotypes derived from Antiquan germ plasm that are resistant to Lepidoptera, we have demonstrated that a unique 33-kD cysteine proteinase accumulates in the whorl in response to larval feeding. The abundance of the proteinase increased dramatically at the site of larval feeding after 1 hr of infestation and continued to accumulate for as long as 7 days. The 33-kD cysteine proteinase was most abundant in the yellow-green portion of the whorl-the normal site of larval feeding and the tissue that has the greatest inhibitory effect on larval growth in bioassays. The proteinase was expressed in response to wounding and was found in senescent leaves. It may be a marker of programmed cell death. The gene coding for the proteinase, mir1, has been transformed into Black Mexican Sweet callus. When larvae were reared on callus expressing the proteinase, their growth was inhibited approximately 60 to 80%. The expression of a cysteine proteinase, instead of a cysteine proteinase inhibitor, may be a novel insect defense mechanism in plants.

Animals↗

PubMed2000

Correlation of the apparent affinities and efficacies of gamma-aminobutyric acid(C) receptor agonists.

gamma-Aminobutyric acid (GABA), trans-4-aminocrotonic acid (TACA), muscimol, imidazole-4-acetic acid (I4AA), cis-4-aminocrotonic acid (CACA), and isoguvacine are all GABA(C) receptor agonists. These compounds have different apparent sensitivities (EC(50)) and efficacies (I(max)) on exogenously expressed human rho1 homomeric GABA(C) receptors. It is not clear if these differences are due to distinct binding affinities and/or distinct gating kinetics. In this study, using a recently developed single oocyte binding technique, we determined the apparent dissociation constants (K(i) values) of these compounds from their IC(50) values for [(3)H]GABA displacement. The apparent K(i) values fell into two distinct groups. The high affinity group was comprised of agonists with longer distances between the nitrogen atom of the amino or imidazole group and the carbon atom of the carboxyl or isoxazole group. The single oocyte binding technique, in conjunction with two-electrode voltage clamp, has allowed a direct correlation of the apparent affinity, efficacy, and potency of agonists on intact functional GABA(C) receptors. The correlation and coupling of these parameters are discussed in terms of a simple proposed activation mechanism.

Animals↗

PubMed2000

Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta.

The Zta protein is a key transactivator involved in initiating the Epstein-Barr virus (EBV) lytic cascade. In addition to transactivating many viral genes, Zta has the capacity to influence host cellular signals by binding to promoter regions or by interacting with several important cellular factors. Based on the observation that tyrosine kinases play central roles in determining the fate of cells, a kinase display assay was used to investigate whether cells expressing Zta have an altered pattern of kinase expression. The assay revealed that TRK-related tyrosine kinase (TKT) is expressed at significant levels in Zta transfectants but not in control cells. Additional evidence was obtained from Northern and Western blotting. Importantly, the upregulation of phosphorylated TKT and TKT downstream effector matrix metalloproteinase 1 in Zta transfectants hinted that TKT might initiate a signaling cascade in Zta-expressing cells. In addition, deletion analysis of the Zta protein revealed that the transactivation and dimerization domains were both essential for the upregulation of TKT transcription. Moreover, correlation of expression levels of Zta and TKT transcripts in nasopharyngeal carcinoma biopsy specimens was clearly demonstrated by quantitative PCR (Q-PCR), which provides the first evidence for an effect of Zta on cellular gene expression in vivo. These findings offer insight into the virus-cell interactions and may help us elucidate the role of EBV in tumorigenesis.

Cell Line, Transformed↗

PubMed2000

Activation of V(D)J recombination induces the formation of interlocus joints and hybrid joints in scid pre-B-cell lines.

V(D)J recombination is the mechanism by which antigen receptor genes are assembled. The site-specific cleavage mediated by RAG1 and RAG2 proteins generates two types of double-strand DNA breaks: blunt signal ends and covalently sealed hairpin coding ends. Although these DNA breaks are mainly resolved into coding joints and signal joints, they can participate in a nonstandard joining process, forming hybrid and open/shut joints that link coding ends to signal ends. In addition, the broken DNA molecules excised from different receptor gene loci could potentially be joined to generate interlocus joints. The interlocus recombination process may contribute to the translocation between antigen receptor genes and oncogenes, leading to malignant transformation of lymphocytes. To investigate the underlying mechanisms of these nonstandard recombination events, we took advantage of recombination-inducible cell lines derived from scid homozygous (s/s) and scid heterozygous (s/+) mice by transforming B-cell precursors with a temperature-sensitive Abelson murine leukemia virus mutant (ts-Ab-MLV). We can manipulate the level of recombination cleavage and end resolution by altering the cell culture temperature. By analyzing various recombination products in scid and s/+ ts-Ab-MLV transformants, we report in this study that scid cells make higher levels of interlocus and hybrid joints than their normal counterparts. These joints arise concurrently with the formation of intralocus joints, as well as with the appearance of opened coding ends. The junctions of these joining products exhibit excessive nucleotide deletions, a characteristic of scid coding joints. These data suggest that an inability of scid cells to promptly resolve their recombination ends exposes the ends to a random joining process, which can conceivably lead to chromosomal translocations.

Abelson murine leukemia virus↗

PubMed2000

Endogenous tachykinins cause bradycardia by stimulating cholinergic neurons in the isolated guinea pig heart.

The purpose of this study was to determine if endogenous tachykinins can cause bradycardia in the isolated perfused guinea pig heart through stimulation of cholinergic neurons. Capsaicin was used to stimulate release of tachykinins and calcitonin gene-related peptide (CGRP) from cardiac afferents. A bolus injection of 100 nmol capsaicin increased heart rate by 26 +/- 7% from a baseline of 257 +/- 14 beats/min (n = 6, P < 0.01). This positive chronotropic response was converted to a minor bradycardic effect in hearts with 1 microM CGRP-(8-37) present to block CGRP receptors. The negative chronotropic response to capsaicin was markedly potentiated in another group of hearts with the further addition of 0.5 microM neostigmine to inhibit cholinesterases. In this group, capsaicin decreased heart rate by 30 +/- 10% from a baseline of 214 +/- 6 beats/min (n = 8, P < 0.05). This large bradycardic response to capsaicin was inhibited by 1) infusion of neurokinin A to desensitize tachykinin receptors or 2) treatment with 1 microM atropine to block muscarinic receptors. The latter observations implicate tachykinins and acetylcholine, respectively, as mediators of the bradycardia. These findings support the hypothesis that endogenous tachykinins could mediate axon reflexes to stimulate cholinergic neurons of the intrinsic cardiac ganglia.

Acetylcholine↗

PubMed2000

Effects of combined superoxide dismutase and catalase on somatosensory evoked potentials and neuropathologic changes in asphyxiated newborn lambs.

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb. In addition, the hypothesis that treatment with the oxygen free radical scavenging enzymes superoxide dismutase and catalase would enhance postasphyxia recovery of evoked potentials and ameliorate pathologic injury was tested. Electrophysiologic and pathologic abnormalities after asphyxia were demonstrated, but treatment with oxygen radical scavengers had no effect on these abnormalities.

Animals↗

PubMed2000

Treatment of murine lupus with cDNA encoding IFN-gammaR/Fc.

IFN-gamma, a pleiotropic cytokine, is a key effector molecule in the pathogenesis of several autoimmune diseases, including lupus. Importantly, deletion of IFN-gamma or IFN-gammaR in several lupus-predisposed mouse strains resulted in significant disease reduction, suggesting the potential for therapeutic intervention. We evaluated whether intramuscular injections of plasmids with cDNA encoding IFN-gammaR/Fc can retard lupus development and progression in MRL-Fas(lpr) mice. Therapy significantly reduced serum levels of IFN-gamma, as well as disease manifestations (autoantibodies, lymphoid hyperplasia, glomerulonephritis, mortality), when treatment was initiated at the predisease stage, particularly when IFN-gammaR/Fc expression was enhanced by electroporation at the injection site. Remarkably, disease was arrested and even ameliorated when this treatment was initiated at an advanced stage. This therapy represents a rare example of disease reversal and makes application of this nonviral gene therapy in humans with lupus (and perhaps other autoimmune/inflammatory conditions) highly promising.

Animals↗