Low frequencies of mitochondrial DNA mutations cause cardiac disease in the mouse.
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Alanine↗
Biomedical subjects
S W Chang
Publications and source records attributed to S W Chang.
Corneal light scattering with stromal reformation after laser in situ keratomileusis and photorefractive keratectomy.
OBJECTIVE: To correlate corneal light scattering with keratocyte and extracellular matrix reformation after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). SETTING: Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA. METHODS: Sixteen pigmented rabbit eyes were randomly divided into 2 groups. Group 1 (n = 8) had a 5.0 mm, -10.0 diopter (D) LASIK treatment and Group 2 (n = 8), a 5.0 mm, -10.0 D surface PRK treatment after mechanical epithelial debridement. The stromal surface exposed at surgery was stained with dichlorotriazinylaminofluorescein (DTAF) solution. Slitlamp biomicroscopic and objective measurement of corneal light scattering using a scatterometer were performed 1 and 2 days and 1, 2, 3, 4, 8, and 12 weeks after surgery. In each group, 2 corneas were harvested at 1 week and 1 month and 4 corneas were harvested at 12 weeks. Tissue sections were examined by light and fluorescence microscopy. The percentage of newly formed stromal tissue was calculated and correlated with the scatterometry index. RESULTS: In Group 1, corneas remained clear and healed without significant scarring throughout the study. In Group 2, subepithelial scarring was noted. Extracellular matrix reformation peaked at 1 month and showed a slight regression thereafter. The percentage of extracellular matrix reformation was strongly correlated with the scatterometry index (r = .86, P < .001). CONCLUSIONS: In this study, significant subepithelial stromal tissue reformation followed PRK. The percentage of extracellular matrix reformation correlated well with the objective corneal light scattering measurements.
Animals↗
Reducing financial barriers to HIV-related medical care: does the Ryan White CARE Act make a difference?
We evaluated whether the Ryan White CARE Act, which funds medical care and supportive services for low-income HIV-infected persons, equalizes health service use in San Francisco. Clients at nine CARE (n = 300) and four non-CARE (n = 172) funded sites completed self-administered questionnaires. There were no significant differences between CARE and non-CARE clients with respect to physician visits, hospitalization or emergency room use in the previous year after adjusting for sociodemographic characteristics and health status. Unemployment and poor health independently predicted higher medical service use. CARE appears to reduce financial barriers to medical services.
Adult↗
A vector DNA vaccine encoding pseudorabies virus immediate early protein demonstrates partial protection in mice against lethal virus challenge.
An earlier study in our laboratory provided evidence that pseudorabies virus (PrV) immediate early protein (IE180) may contribute to the overall immune response against PrV. To examine the response by IE180 more closely, we initiated a vaccine trial in mice with a vector DNA construct that contains the gene encoding for IE180, designated pcDNAIE180. The DNA vaccine was delivered in gold microcarriers using a Helios Gene Gun, and 70% of BALB/c mice given the DNA vaccine (2 microg/mouse) seroconverted within 2 weeks. The remaining negative mice seroconverted after a single vaccine booster. Essentially similar results were obtained on vaccination of C57BL/6 mice, whereas C3H/HeJ mice remained negative after the first vaccination, but responded after a booster. Seven months after immunization with pcDNAIE180, an overall 25% of BALB/c, C3H/HeJ, and C57BL/6 mice receiving a lethal PrV challenge were protected. In addition, a significant passive transfer of IE180-specific antibodies to the offspring from pregnant mice vaccinated with pcDNAIE180 was observed. Interestingly, a moderate level of protection (27.6%) was also observed when these offspring received a lethal PrV challenge. Moreover, an enhancement of immune responses and a twofold increase in the level of protection were observed in mice that received a second vaccine booster by gene gun 8 months after the first vaccination. Together, these data support the theory that IE180 may indeed play a role in the overall protective immunity against PrV.
Animals↗
Analysis of corneal topography after excimer laser photorefractive keratectomy.
Excimer laser photorefractive keratectomy (PRK) is an effective treatment for myopia. We investigated the magnitude of optical zone decentration and qualitative patterns of corneal topography after this treatment. We performed computer-assisted videokeratography on 44 myopic eyes (29 patients) that had undergone PRK before and 1, 6, and 12 months after the procedure. Associations of clinical outcomes with decentration and topographic patterns were assessed. The normalized scale of the topography 1 month postoperatively showed a mean decentration of 0.33 +/- 0.23 mm (range 0-0.9). Thirty-four eyes had decentration of less than 0.50 mm; 10 had an ablation zone decentered from 0.5 to 0.9 mm. Analysis of geometric mean visual acuities between eyes with less than 0.5 mm decentration and those with 0.5 to 0.9 mm decentration demonstrated minimal differences. No eye was decentered more than 1 mm. Four main ablation patterns were noted on subtraction analysis: homogeneous, semicircular, keyhole, and central island. Over time, the number of eyes with a homogeneous pattern increased. Eyes with a homogeneous ablation pattern had significantly better uncorrected visual acuity than those with other patterns. The mean visual acuity was 20/29.1 in the homogeneous group and 20/38.5 in the pooled irregular group 1 month postoperatively (p < 0.05). There was no significant difference among the four ablation patterns at 6 or 12 months after PRK. Topographic patterns were not significantly associated with best-corrected vision.
Cornea↗
Factors associated with women's adherence to mammography screening guidelines.
OBJECTIVE: To examine individual and environmental factors associated with adherence to mammography screening guidelines. DATA SOURCES: A unique data set that combines a national probability sample (1992 National Health Interview Survey); a national probability sample of mammography facility characteristics (1992 National Survey of Mammography Facilities); county-level data on 1990 HMO market share; and county-level data on the supply of primary care providers (1991 Area Resource File). STUDY DESIGN: The design was cross-sectional. DATA EXTRACTION/ANALYSIS: Data sets were linked to create an individual-level sample of women ages 50-74 (weighted n = 2,026). We used multipart, sequential logistic regression models to examine the predictors of having ever had mammography, having had recent mammography, and adherence to guidelines. We categorized women as adherent if they reported a lifetime number of exams appropriate for their age (based on screening every two years) and they reported having had an exam in the past two years. PRINCIPAL FINDINGS: Only 27 percent of women had the age-appropriate number of screening exams (range 16 percent-37 percent), while 59 percent of women had been screened within two years. Women were significantly more likely to adhere to screening guidelines if they reported participating with their doctor in the decision to be screened; were younger; had smaller families, higher education and income, and a recent Pap smear; reported breast problems; and lived in an area with a higher percentage of mammography facilities with reminder systems, no shortage of primary care providers, higher HMO market share, and higher screening charges. CONCLUSIONS: A small percentage of women adhere to screening guidelines, suggesting that adherence needs to become a focus of clinical, programmatic, and policy efforts.
Aged↗
Lung capillary changes in hepatic cirrhosis in rats.
The hypoxemia of the hepatopulmonary syndrome may result from dilated intrapulmonary vascular segments. Knowledge of the size, density, and branching frequency of the lung capillaries might confirm this hypothesis and suggest that the pathogenesis may involve vascular dilatation or angiogenesis. To investigate these changes, the common bile duct of rats was tied off to cause biliary cirrhosis. Later (4 wk), the pulmonary vasculature of these animals was cast, and the casts were studied with scanning electron microscopy. In the ligated animals, evidence for enhancement of the bronchial to pulmonary circulation was found: cast vasa vasorum of the pulmonary arteries and cast bronchial veins emptying into pulmonary veins. Ligated animals had more adherent intracapillary cells per alveolus than the sham-operated animals. The diameters of all capillary beds were larger in the ligated animals. The alveolar capillary density was increased, but the branching frequency was not. A few areas suggesting angiogenesis were found. Induction of biliary cirrhosis enhances the pulmonary-systemic circulation, increases intracapillary adherent cells, capillary diameter, and density, and may be associated with angiogenesis.
Animals↗
Nitrous oxide synthase expression in placenta of preeclampsia.
To compare the expression of endothelial nitrous oxide synthase (e-NOS), which plays a major role in vasoconstriction, in preeclampsia with that in the normotensive placenta and to identify whether or not e-NOS actually influences the pathogenesis of preeclampsia, we have studied the distribution and intensity of the endothelial isoform of NOS expression in preeclampsia (n = 121) and normal (n = 14) pregnancies. Archival paraffin-embedded tissues were immunostained with a polyclonal e-NOS antibody. E-NOS was stained predominantly in the endothelial cells of the umbilical cord and along the surface of the villi, especially within the cytoplasms of the syncytiotrophoblasts with a granular and punctuated pattern, but not in the trophoblastic island or in the intravillous capillaries. The degree of e-NOS expression in pregnancy-induced hypertension (PIH) was significantly lower than in normotensive placenta, and moreover in the patients lacking abruptio. The expression of e-NOS in preeclampsia has some correlation with patient age. In conclusion, the degree of e-NOS expression in cotyledon from PIH is far less than from control, it means a kind of hemodynamic alteration of the fetoplacental circulation in preeclampsia.
Adult↗
Racial differences in timeliness of follow-up after abnormal screening mammography.
BACKGROUND: To determine whether patient race was associated with timeliness of follow-up after abnormal screening mammography, a retrospective record review of diagnostic tests for women with abnormal screening mammography from a Northern California mobile van program was conducted. METHODS: The study included 317 women between the ages of 33 and 85 who were reported to have abnormal screening mammography between July 1993 and May 1994. Measurements included patient demographics, screening mammography interpretation, follow-up diagnostic tests, and dates of diagnostic evaluation. RESULTS: Women with abnormal screening mammography underwent a wide variety of diagnostic evaluations. Nonwhite women had significantly longer time (median time, 19 days) from date of index abnormal screening mammography to final disposition compared with white women (median time, 12 days). This racial difference was primarily due to the longer interval between index abnormal screening mammography and first diagnostic test (median time, 15 days for nonwhite women versus 7 days for white women, P < 0.001). The difference persisted when adjusting for patient age, family history of breast cancer, report of palpable mass, and income. The racial difference was similarly significant for each nonwhite subgroup (African American, Latina, and Asian) when compared with white women (P < 0.01). CONCLUSIONS: Reasons for less timely follow-up of abnormal mammography among nonwhite women need to be identified. Delays that may be instigated by the patient or be due to her physician or system of care need to be explored further.
Adult↗
Pulmonary intravascular phagocytosis in liver disease.
Pulmonary intravascular phagocytosis, the uptake of circulating particles by lung cells, has been detected in rats with chronic biliary cirrhosis and in humans with malignancy and liver diseases. Clinical and experimental evidence supporting the association of pulmonary intravascular phagocytosis with liver cirrhosis is reviewed, and its relationship to pulmonary intravascular macrophage is discussed. A hypothesis is asserted that the induction of pulmonary intravascular macrophage in liver cirrhosis leads to increased susceptibility to adult respiratory distress syndrome in these patients.
Animals↗
Corneal epithelial recovery following photorefractive keratectomy.
AIMS: To further understand the morphological and functional recovery of corneal epithelium following excimer laser photorefractive keratectomy (PRK). METHODS: The right eyes (group 1) of 15 male, New Zealand white rabbits weighing 2-3 kg underwent PRK. The left eye of each rabbit (group 2) underwent simple mechanical de-epithelialisation and were examined as treated controls. Both eyes of another eight rabbits (group 3) served as untreated controls. All eyes underwent a corneal epithelial permeability study by fluorophotometry at 2, 4, and 8 weeks after surgery. Five animals in groups 1 and 2 were sacrificed at 9, 10, and 12 weeks after surgery. The animals in group 3 were sacrificed at the end of the 12 week experimental period. Both eyes of each sacrificed animal were enucleated immediately and processed for both haematoxylin and eosin stain and electron microscopic study. The electron micrograph was magnified to 14,000x and the extent of hemidesmosome formation was quantified and analysed. RESULTS: The corneal epithelial barrier to sodium fluorescein was subnormal and returned to a normal barrier state 4 weeks after PRK in group 1 whereas it was normal in group 2 throughout the examination period. The extent of hemidesmosome formation was abundant yet subnormal in both groups 1 and 2 up to 12 weeks, when compared with that in group 3. CONCLUSION: The corneal epithelium regained its functional barrier 4 weeks after PRK in rabbits while the extent of hemidesmosome formation was still subnormal 12 weeks after mechanical de-epithelialisation, with or without PRK.
Animals↗
Excimer laser photorefractive keratectomy for myopia.
To evaluate the safety, effectiveness and stability of excimer laser photorefractive keratectomy (PRK) treatment, we studied its posttreatment results in 44 normal-sighted myopic eyes where a 193-nm emission wavelength excimer laser was used to correct myopia. The eyes were divided into three groups according to the preoperative refractive error and attempted correction: group I, preoperative myopia < or = 6.00 diopters (D), full correction; group II, preoperative myopia between 6.00 and 8.00 D, full correction; group III, preoperative myopia > 8.00 D, attempted correction of 8.00 D. Percentages of relative spherical equivalents (ie, observed spherical equivalent -- expected spherical equivalent) within +/- 1.0 D 3 months after treatment were 95% in group I, 64% in group II and 67% in group III. Uncorrected visual acuity of 20/40, or better, was achieved in 100% of eyes in group I, and 92% in group II at 6 months. Initial overcorrection followed by myopic regression was observed in all groups. The refractive outcome in our study was stable 3 months after surgery. Anterior stromal haze was mild and disappeared gradually 3 months postoperatively. The greater the diopter correction needed, the higher the grade of corneal haze (p < 0.01). There were no significant complications. The results of this study demonstrated that excimer laser PRK appears to be a reasonably predictable and stable procedure to correct low to moderate myopia.
Adult↗
Health insurance and use of medical services by men infected with HIV.
Among 178 HIV-infected men from the San Francisco City Clinic Cohort (SFCCC), we examined the association between health insurance and use of outpatient services and treatment. For men with private insurance, we also assessed the frequency of avoiding the use of health insurance. Men without private insurance reported fewer outpatient visits than men with fee-for-service or managed-care plans. Use of zidovudine for eligible men was similar for those with fee-for-service plans (74%), managed-care plans (77%), or no insurance (61%). Use of Pneumocytstis carinii pneumonia prophylaxis was similar for those with fee-for-service (93%) and managed-care plans (83%) but lower for those with no insurance (63%). Of 149 men with private insurance, 31 (21%) reported that they had avoided using their health insurance for medical expenses in the previous year. In multivariate analysis, the independent predictors of avoiding the use of insurance were working for a small company and living outside the San Francisco Bay Area. Having private insurance resulted in higher use of outpatient services, but the type of private insurance did not appear to affect the use of service or treatment. Fears of loss of coverage and confidentiality may negate some benefits of health insurance for HIV-infected persons.
Adult↗
Acyclovir treatment for linear endotheliitis on grafted corneas.
Two patients with previous corneal transplants developed unusual rejection-like episodes of the grafted cornea. Both had a migrating line of keratic precipitates and stromal edema involving both the donor and recipient corneas. Intensive steroid treatment attained little effect, but oral acyclovir treatment dramatically suppressed the disease process. The facts suggest that a virus-related immune mechanism against both the donor and recipient endothelia, rather than simple allograft rejection, may have been responsible for the clinical presentations. Oral acyclovir therapy might be considered in patients with steroid-nonresponsive corneal endotheliitis mimicking allograft rejection.
Acyclovir↗
Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs.
A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.
Animals↗
Leukotoxin, 9,10-epoxy-12-octadecenoate causes pulmonary vasodilation in rats.
Leukotoxin (Lx), a cytochrome P-450-dependent metabolite of linoleate synthesized by neutrophils or synthesized by OH- and linoleate in neutrophil cell membranes, has been recovered in lung lavages of patients with the adult respiratory distress syndrome. We studied the direct vasoactive effects of Lx and linoleate, its parent compound, in the rat pulmonary circulation. In isolated rat lungs perfused at constant flow with a physiological salt solution, Lx (but not linoleate) caused a biphasic response, an initial transient vasoconstriction followed by a more prolonged vasodilation. The latter response was only evident when the pulmonary vascular tone was increased with either alveolar hypoxia (0% O2) or KCl (20 mM). The pressor response to angiotensin II was also attenuated in the presence of Lx. The vasodilatory response in perfused lungs was attenuated by methylene blue (2 x 10(-5) M), a putative inhibitor of the soluble guanylate cyclase but not by pretreatment with meclofenamate (10(-5) M), a cyclooxygenase inhibitor. In isolated pulmonary arterial (PA) rings preconstricted either with phenylephrine (5 x 10(-9) M), endothelin-1 (10(-8) M), or KCl (30 mM), Lx (but not linoleate) caused dose-dependent relaxation. The relaxing effect of Lx on endothelium-intact rings was attenuated by NG-monomethyl-L-arginine or methylene blue. The magnitude of the hypoxic contraction of PA rings was attenuated in the presence of Lx. Whereas the mechanism of Lx-induced vasoconstriction is not clear, we conclude that Lx causes vasodilation in rat lungs and that the vasodilatory component is to a large degree endothelium-derived relaxing factor-dependent.
Animals↗
Leukotoxin, 9,10-epoxy-12-octadecenoate causes edematous lung injury via activation of vascular nitric oxide synthase.
We examined the mechanism of leukotoxin, 9,10-epoxy-12-octadecenoate (Lx)-induced lung injury in blood-free, physiological salt solution-perfused rat lungs under constant flow conditions. Mean pulmonary arterial (Ppa) and pulmonary capillary pressure (Pcap, estimated by the double-occlusion method), wet lung weight (WLW), pulmonary capillary filtration coefficient (Kfc), lung perfusate lactate dehydrogenase (LDH) activity, and nitrite levels were assessed. Bolus injection of Lx (200 microM) caused insidious and significant lung weight gain, which was not associated with remarkable elevation of Ppa or Pcap but was associated with an increase of perfusate LDH activity and nitrite levels. Lx (20 microM) elevated Kfc, indicating that Lx had affected pulmonary vascular permeability. Because Lx causes endothelium dependent pulmonary vasodilation, we studied the effect of NG-monomethyl-L-arginine (L-NMMA), NG-monomethyl-D-arginine (D-NMMA), superoxide dismutase (SOD), human oxyhemoglobin (oxyHb), and methylene blue (MB) on Lx-induced lung injury. L-NMMA, SOD, and oxyHb, but not MB or D-NMMA, protected the lungs against Lx (200 microM)-induced injury. Lx increased pulmonary vascular permeability and caused lung injury. Because both nitric oxide synthase inhibitors and SOD inhibited the Lx-induced lung injury, it is possible that peroxynitrite is involved in the mechanism whereby Lx causes lung injury.
Amino Acid Oxidoreductases↗
Endothelin-1 potentiates leukotoxin-induced edematous lung injury.
We tested the hypothesis that leukotoxin (Lx), a cytochrome P-450-dependent linoleate product of leukocytes, can stimulate the release of endothelin-1 (ET-1) from the lung and further that exogenous ET-1 synergizes with Lx to produce edematous lung injury. In isolated rat lungs perfused with Earle's balanced salt solution, Lx (10 mumol) alone caused lung edema and increased the perfusate and lung tissue ET-1 levels. The combination of ET-1 (5 nM) and Lx (5 mumol), at concentrations that by themselves did not increase wet lung weight, significantly increased wet lung weight, wet-to-dry lung weight ratio, as well as the lung effluent lactate dehydrogenase activity. Pretreatment with BQ-123 (5 x 10(-6) M), an endothelin A receptor antagonist that significantly attenuated the ET-1 (5 nM)-induced increase in pulmonary arterial pressure (Ppa) and pulmonary capillary pressure (Ppc), suppressed the edematous lung injury generated by the combination of ET-1 and Lx, suggesting that the edema-enhancing effect of ET-1 in Lx-treated lungs occurred through endothelin A receptor-dependent elevation of Ppa and Ppc. Elevation of the pulmonary venous pressure in Lx-treated lungs (13.5 cmH2O) mimicked the effect of ET-1 on Ppa and Ppc and produced a degree of lung edema that was comparable to that after combined ET-1 + Lx treatment but without increase in the perfusate lactate dehydrogenase. These data support the idea that ET-1 and Lx promote lung edema in a synergistic fashion.
Animals↗