Biomedical subjects

T Li

Publications and source records attributed to T Li.

At least 235 records · Page 13Linked to original sources

PubMed1999

Study on genital tract Chlamydia trachomatis and gonococcal infection in Han and minority (Naxi and Dai) women in China's two provinces.

OBJECTIVES: To estimate the prevalence of lower female genital tract chlamydial (GTC) and gonococcal infection in 3 different ethnic groups in China, and to analyze the risk factors influencing these infections. METHODS: A cross-sectional survey + physical and laboratory examinations. 1,800 married women aged 18-35 Han (600, from Dujiangyan city, Sichuan), Naxi (600, from Yanyuan county, Sichuan), and Dai (600, from Jinghong Prefecture, Yunnan) were investigated between March 1996 to March 1997. Information was obtained about their personal history, socioeconomic status, medical history, STDs, sexual history, contraceptive history, results of both examinations. Tabulation, t-test, Chi-square test, multiple-logistic models were used to analyze the data. RESULTS: 3.2% of Han, 12.8% of Naxi and 4.5% of Dai women tested positive for gonococci; and 9.1% of Han, 16.7% of Naxi and 27.5% of Dai women tested positive for GTC infection. The differences of GTC and gonococcal infections between Han and Naxi, and Han and Dai women were significant. CONCLUSIONS: STDs are common in China today; both GTC and gonoccocal infections are related to non-use of condom, having sexual partners other than husband, number of abortions, and low education; and condom has a function in prevention of STDs.

Adolescent↗

PubMed1999

Strains of Actinomyces naeslundii and Actinomyces viscosus exhibit structurally variant fimbrial subunit proteins and bind to different peptide motifs in salivary proteins.

Oral strains of Actinomyces spp. express type 1 fimbriae, which are composed of major FimP subunits, and bind preferentially to salivary acidic proline-rich proteins (APRPs) or to statherin. We have mapped genetic differences in the fimP subunit genes and the peptide recognition motifs within the host proteins associated with these differential binding specificities. The fimP genes were amplified by PCR from Actinomyces viscosus ATCC 19246, with preferential binding to statherin, and from Actinomyces naeslundii LY7, P-1-K, and B-1-K, with preferential binding to APRPs. The fimP gene from the statherin-binding strain 19246 is novel and has about 80% nucleotide and amino acid sequence identity to the highly conserved fimP genes of the APRP-binding strains (about 98 to 99% sequence identity). The novel FimP protein contains an amino-terminal signal peptide, randomly distributed single-amino-acid substitutions, and structurally different segments and ends with a cell wall-anchoring and a membrane-spanning region. When agarose beads with CNBr-linked host determinant-specific decapeptides were used, A. viscosus 19246 bound to the Thr42Phe43 terminus of statherin and A. naeslundii LY7 bound to the Pro149Gln150 termini of APRPs. Furthermore, while the APRP-binding A. naeslundii strains originate from the human mouth, A. viscosus strains isolated from the oral cavity of rat and hamster hosts showed preferential binding to statherin and contained the novel fimP gene. Thus, A. viscosus and A. naeslundii display structurally variant fimP genes whose protein products are likely to interact with different peptide motifs and to determine animal host tropism.

Actinomyces↗

PubMed1999

Isolation and characterization of a sigB deletion mutant of Staphylococcus aureus.

The sigB gene of Staphylococcus aureus, coding for the alternate sigma factor B, has been deleted by allelic replacement mutagenesis. The mutant grew as well as the parent in vitro, although it was deficient in clumping factor, coagulase, and pigment. In two murine and one rat infection model the mutant showed no reduction in virulence.

Animals↗

PubMed1999

Role in cell permeability of an essential two-component system in Staphylococcus aureus.

A temperature-sensitive lethal mutant of Staphylococcus aureus was found to harbor a mutation in the uncharacterized two-component histidine kinase (HK)-response regulator (RR) pair encoded by yycFG; orthologues of yycFG could be identified in the genomes of Bacillus subtilis and other gram-positive bacteria. Sequence analysis of the mutant revealed a point mutation resulting in a nonconservative change (Glu to Lys) in the regulator domain of the RR at position 63. To confirm that this signal transduction system was essential, a disrupted copy of either the RR (yycF) or the HK (yycG) was constructed with a set of suicide vectors and used to generate tandem duplications in the chromosome. Resolution of the duplications, leaving an insertion in either the yycF or the yycG coding region, was achieved only in the presence of an additional wild-type copy of the two open reading frames. Phenotypic characterization of the conditional lethal mutant showed that at permissive growth conditions, the mutant was hypersusceptible to macrolide and lincosamide antibiotics, even in the presence of the ermB resistance determinant. Other mutant phenotypes, including hypersensitivity to unsaturated long-chain fatty acids and suppression of the conditional lethal phenotype by high sucrose and NaCl concentrations, suggest that the role of the two-component system includes the proper regulation of bacterial cell wall or membrane composition. The effects of this point mutation are strongly bactericidal at the nonpermissive temperature, indicating that this pathway provides an excellent target for the identification of novel antibiotics.

Amino Acid Sequence↗

PubMed1999

Overlapping signals for transcription and replication at the 3' terminus of the vesicular stomatitis virus genome.

Transcription and replication signals within the negative-sense genomic RNA of vesicular stomatitis virus (VSV) are located at the 3' terminus. To identify these signals, we have used a transcription- and replication-competent minigenome of VSV to generate a series of deletions spanning the first 47 nucleotides at the 3' terminus of the VSV genome corresponding to the leader gene. Analysis of these mutants for their ability to replicate showed that deletion of sequences within the first 24 nucleotides abrogated or greatly reduced the level of replication. Deletion of downstream sequences from nucleotides 25 to 47 reduced the level of replication only to 55 to 70% of that of the parental template. When transcription activity of these templates was measured, the first 24 nucleotides were also found to be required for transcription, since deletion of these sequences blocked or significantly reduced transcription. Downstream sequences from nucleotides 25 to 47 were necessary for optimal levels of transcription. Furthermore, replacement of sequences within the 25 to 47 nucleotides with random heterologous nonviral sequences generated mutant templates that replicated well (65 to 70% of the wild-type levels) but were transcribed poorly (10 to 15% of the wild-type levels). These results suggest that the minimal promoter for transcription and replication could be as small as the first 19 nucleotides and is contained within the 3'-terminal 24 nucleotides of the VSV genome. The sequences from nucleotides 25 to 47 may play a more important role in optimal transcription than in replication. Our results also show that deletion of sequences within the leader gene does not influence the site of transcription reinitiation of the downstream gene.

5' Untranslated Regions↗

PubMed1999

Effects of methionine on endogenous antioxidants in the heart.

The deficiency of methionine, an essential amino acid, is associated with cardiovascular lesions. Because different types of cardiac pathologies are caused by a decrease in antioxidants, we examined the effects of methionine on myocardial antioxidant enzymes in hemodynamically assessed rats that were treated with methionine (10 mg/ml) in drinking water for 12, 24, and 48 h. Glutathione peroxidase (GSHPx) activity was significantly increased to 150.5 +/- 12.2 and 191.7 +/- 13.7% of the control value at 12 and 24 h, respectively, followed by a decline to 120 +/- 24.6% at 48 h. The mRNA levels of GSHPx at these time points were 151.2 +/- 12.0, 218.7 +/- 35.3, and 173.5 +/- 25.2%, respectively. Superoxide dismutase (SOD) activity was 144.3 +/- 3.7, 114.3 +/- 10.1, and 143.1 +/- 11. 2% at 12, 24, and 48 h, respectively. Catalase (Cat) activity was 272.4 +/- 5.4, 237.8 +/- 16.6, and 224.1 +/- 17.3% of the control value. The expression of Cat and SOD mRNA was unchanged at 12, 24, and 48 h. The lipid peroxidation was decreased by 24.4 +/- 11.2, 54. 9 +/- 0.1, and 6.4 +/- 2.1% at 12, 24, and 48 h, respectively. Methionine had no effect on the ventricular or aortic pressures, heart rate, and myocardial glutathione levels at any of the time points. The study shows that methionine has a significant effect on the myocardial antioxidant enzyme activities, and only changes in GSHPx enzyme activity correlated with the mRNA changes. These antioxidant changes may have a role in the beneficial effects of methionine in pathological rather than physiological conditions.

Animals↗

PubMed1999

Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI.

BACKGROUND AND PURPOSE: Combined echoplanar MRI diffusion-weighted imaging (DWI), perfusion imaging (PI), and magnetic resonance angiography (MRA) can be used to visualize acute brain ischemia and predict lesion evolution and functional outcome. The appearance of a larger lesion by PI than by DWI quantitatively defines a mismatch of potential clinical importance. Qualitative lesion variations exist in the topographic concordance of this mismatch. We examined both the topographic heterogeneity and relative frequency of mismatched patterns in acute stroke using these MRI techniques. METHODS: Acute DWI, PI, and MRA studies of 34 prospectively recruited patients with supratentorial ischemic lesions scanned within 24 hours of stroke onset (range 2.5 to 23.3 hours, 12 patients <6 hours) were analyzed. RESULTS: Ischemic lesions were predominantly in the middle cerebral artery (MCA) territory (94%), with DWI lesions most commonly affecting the insular region. Mismatched patterns with PI lesion larger than DWI lesion occurred in 21 patients (62% overall), in all 4 patients imaged within 3 hours, and in 44% of patients imaged after 18 hours. A patient with a large PI but no DWI lesion and severe clinical deficit at 2.5 hours after stroke onset recovered completely. Regional variations in DWI and PI lesion loci were found, inferring site of proximal MCA occlusion, embolic pathogenesis, and regional arterial reperfusion. CONCLUSIONS: Analysis of the topographic concordance of PI and DWI lesions in acute stroke reveals regional PI lesions without concomitant DWI lesions, which do not necessarily progress to infarction but may suggest stroke pathogenesis and site of current arterial occlusion. Location of DWI lesions may suggest an earlier site of arterial occlusion and regions of maximal perfusion deficit.

Aged↗

PubMed1999

Identification of major ischemic change. Diffusion-weighted imaging versus computed tomography.

BACKGROUND AND PURPOSE: Thrombolytic therapy is not recommended in patients with CT changes of recent major infarction, which has been defined as reduced attenuation or cerebral edema involving >33% of the middle cerebral artery territory (European Cooperative Acute Stroke Study [ECASS] criteria). Diffusion-weighted imaging (DWI) is more sensitive than CT in detecting acute ischemia, and the combination of DWI, MR perfusion imaging, and MR angiography provides additional information from a single examination. We sought to determine whether DWI could identify the presence and extent of major ischemia as well as CT in hyperacute stroke patients. METHODS: Seventeen suspected hemispheric stroke patients were studied with both CT and DWI within 6 hours of symptom onset. None received thrombolytic therapy. The scans were examined separately by 2 neuroradiologists in a blinded fashion for ischemic change and cerebral edema, graded as normal, <33%, or >33% of the MCA territory. Final diagnosis of stroke was determined with the use of standard clinical criteria and T2-weighted imaging at day 90. RESULTS: Sixteen of 17 patients had a final diagnosis of stroke. Acute ischemic changes were seen in all 16 on DWI (100% sensitivity) and in 12 of 16 on CT (75% sensitivity). DWI identified all 6 patients with major ischemia on CT, with excellent agreement between the 2 imaging techniques (kappa=0.88). One patient eligible for thrombolysis on the ECASS CT criteria had major ischemia on DWI. CONCLUSIONS: DWI is more sensitive than CT in the identification of acute ischemia and can visualize major ischemia more easily than CT.

Adult↗

PubMed1999

Serial study of apparent diffusion coefficient and anisotropy in patients with acute stroke.

BACKGROUND AND PURPOSE: We sought to characterize the evolution of apparent diffusion coefficient (ADC) and apparent diffusion anisotropy (ADA) in acute stroke and to evaluate their roles in predicting stroke evolution and outcome. METHODS: We studied 26 stroke patients acutely (<24 hours), subacutely (3 to 5 days), and at outcome (3 months). Ratios of the ADC and ADA within a region of infarction and the normal contralateral region were evaluated and compared with the Canadian Neurological Scale, Barthel Index, and Rankin Scale. RESULTS: Heterogeneity in ADC and ADA evolution was observed not only between patients but also within individual lesions. Three patterns of ADA evolution were observed: (1) elevated ADA acutely and subacutely; (2) elevated ADA acutely and reduced ADA subacutely; and (3) reduced ADA acutely and subacutely. At outcome, reduced ADA with elevated ADC was observed generally. We identified 3 phases of diffusion abnormalities: (1) reduced ADC and elevated ADA; (2) reduced ADC and reduced ADA; and (3) elevated ADC and reduced ADA. The ADA ratios within 12 hours correlated with the acute Canadian Neurological Scale (r=0.46, P=0.06), subacute Canadian Neurological Scale (r=0.55, P=0.02), outcome Barthel Index (r=0.62, P=0.01), and Rankin Scale (r=-0.77, P<0.0005) scores. CONCLUSIONS: Combined ADC and ADA provide differential patterns of stroke evolution. Early ADA changes reflect cellular alterations in acute ischemia and may provide a potential marker to predict stroke outcome.

Acute Disease↗

PubMed1999

Total synthesis and chemical biology of the sarcodictyins.

The sarcodictyins A-F and eleutherobin comprise a family of marine-derived diterpenoids with potent cytotoxicities against various tumor cell lines. Investigations have revealed that several of these compounds exert their cytotoxic effects through tubulin binding in a mechanism analogous to that of the clinical anticancer drug Taxol. The biological importance, challenging molecular architecture, and relative scarcity of these natural products have prompted several groups to undertake their total chemical synthesis. In this review, we summarize the current synthetic efforts and examine the preliminary structure-activity relationships which have emerged from early combinatorial libraries.

Animals↗

PubMed1999

Asthma care practices, perceptions, and beliefs of Chicago-area asthma specialists. Chicago Asthma Surveillance Initiative Project Team.

INTRODUCTION: Few studies have closely explored how well physicians who consider themselves specialists in asthma adhere to national guideline recommendations for the diagnosis and treatment of asthma. The purpose of this study is to characterize current knowledge, attitudes, beliefs, and self-reported treatment practices of the asthma specialists working in one large metropolitan area. METHODS: In 1997, a cross-sectional survey was mailed to asthma specialists (allergists or pulmonologists) engaged in direct patient care with a practice location in the Chicago area (Cook County or one of the five surrounding counties). An approximately 50% random sample of asthma specialists was surveyed. The survey included items on (1) asthma diagnosis; (2) clinical monitoring of asthma patients; (3) pharmacologic and nonpharmacologic asthma treatment; (4) opinions and beliefs about asthma treatment options and reasons for referrals; (5) involvement in continuing medical education; (6) experiences with managed care; (7) use of asthma practice guidelines; (8) demographic information about the respondents; and (9) characteristics of the practice settings. RESULTS: A total of 113 eligible surveys were returned (response rate, 72.0%). Ninety-nine percent of the respondents indicated they would prescribe inhaled corticosteroids for patients > or = 5 years old with moderate persistent asthma, and 85.5% would prescribe them for patients < 5 years old. The respondents reported that 71.2% of their patients with moderate or severe persistent asthma were routinely given written treatment plans. The use of these plans was reported more frequently by allergists than pulmonologists (77.6% vs 58.9%, p = 0.01). Nearly half of the respondents were involved in the development of hospital-based asthma programs; fewer (14.9%) were involved in developing asthma programs for managed care organizations. A majority (63.4%) of the physicians had given a formal professional education presentation on asthma in the past year. A majority of the respondents who care for patients under managed care contracts reported that these patients have encountered barriers to access in seeking specialty care. CONCLUSION: The results suggest that asthma specialists in the Chicago area are providing asthma care that is, in many ways, consistent with national guidelines. However, there are also important differences in care that are not consistent with the guideline recommendations. Perhaps even more notable are differences in reported asthma care between the two subspecialty groups of allergists and pulmonologists. The effect of these differences on the management of persons with asthma is not known. It is hoped that information from this community-based survey will serve to catalyze discussions among Chicago-area asthma specialists as to how they might envision improving care for persons with asthma in their community.

Adolescent↗

PubMed1999

Characteristics of asthma care provided by hospitals in a large metropolitan area: results from the Chicago Asthma Surveillance Initiative.

INTRODUCTION: Little is known of the approaches of United States hospitals to the management of persons with asthma. The purpose of this study is to characterize the extent to which hospitals within a large community have implemented various types of asthma-specific health-care delivery processes. METHODS: A cross-sectional, self-administered survey was mailed to a "key informant" in asthma care at each of the hospitals in the Chicago area. The survey instrument covered the following content areas: asthma-related inpatient services, asthma-related outpatient services, selected asthma-related quality improvement activities, and asthma-related community outreach. The survey was administered between August 1996 and January 1997. RESULTS: Data were collected from respondents at 59 of the 89 eligible hospitals, yielding a response rate of 66.3%. Of the responding hospitals, 42.4% indicated they had clinical practice guidelines for inpatient asthma management, and 37.3% reported using critical pathways. Four selected aspects of bedside care were also explored. All of the responding hospitals reported routine provision of nebulization therapy at the bedside, and nearly all routinely obtained peak flow measurements (96.6%). In the area of patient instruction, 93.2% provided bedside evaluation of proper inhaler technique, and 86.4% routinely provided instruction on the use of peak flowmeters. Only 54.0% of the hospitals reported routinely administering some type of asthma education program prior to discharge. The hospitals with clinical practice guidelines in place were also more likely to have critical pathways (p < 0.01); to have asthma-specific ICU policies/guidelines/critical pathways (p < 0.01); to provide bedside instruction on the use of peak flowmeters (p < 0.01); to provide an asthma education (p < 0.01) prior to discharge; and to conduct utilization review. Very few hospitals indicated that they had community outreach programs for asthma care. CONCLUSION: The results of this survey suggest that among Chicago-area hospitals appropriate bedside care for persons with asthma is provided, but there are large variations in other types of asthma services and programs. The hospitals that have adopted asthma clinical practice guidelines are more likely to have other asthma-specific quality improvement activities than hospitals without guidelines. This relationship between use of guidelines and quality of services needs further exploration, as it may prove to be an important marker for hospitals with staff that are interested in improving asthma care.

Adolescent↗

PubMed1999

Asthma care practices in Chicago-area emergency departments. Chicago Asthma Surveillance Initiative Project Team.

INTRODUCTION: Emergency departments (EDs) represent an important source of asthma care, yet there are few studies detailing how ED asthma practices vary and to what extent EDs meet expectations of national asthma guidelines. The purpose of this study is to characterize ED care for persons with asthma in a single large community. METHODS: During 1996 and 1997, a cross-sectional, self-administered survey to characterize asthma care practices was conducted among medical directors of the 89 EDs serving the Chicago metropolitan area (six counties). The survey topic areas included asthma-specific demographics and selected utilization statistics; assessment practices; treatment practices; discharge and follow-up activities; and familiarity with, attitudes toward, and utilization of guidelines/ protocols. RESULTS: Sixty-four EDs completed surveys, for a response rate of 71.9%. Ninety-four percent of the respondents were ED medical directors. As part of assessment, peak flow measurements, while common, were used less frequently than pulse oximetry. The average (+/- SE) estimated length of stay for asthma care was 3.0 +/- 0.1 h, and average disposition time (ie, the decision to admit) was 2.5 +/- 0.2 h. Systemic steroids (either i.v. or p.o.) were estimated to be given to 73.2 +/- 3.9% of patients during their ED visits. Systemic steroids were prescribed for 55.9 +/- 3.5% of patients at time of discharge. Only 57.0 +/- 5.4% of patients were estimated to have received any type of written asthma educational materials. Approximately 25% of patients were reported to have been given a detailed follow-up appointment at the time of discharge. CONCLUSION: The results reveal that the medical directors reported many of the Chicago-area EDs as providing asthma care that is consistent with key aspects of national guidelines. However, in certain critical areas of care, the EDs demonstrate a high degree of variation, often with the community falling short of guideline recommendations. By identifying these variations in asthma care, it is now possible to target specific goals for community-wide asthma quality improvement among the EDs in the Chicago metropolitan area.

Adolescent↗

PubMed1999

Development of a survey of asthma knowledge, attitudes, and perceptions: the Chicago Community Asthma Survey. Chicago Asthma Surveillance Initiative Project Team.

Little is known about the general public's perception of the diagnosis of asthma and the impact of asthma on individuals, their families, and their communities. In addition, there appear to be no published survey instruments specifically designed to gain insights into how the general public perceives asthma. The purpose of this paper is to describe the development of such an instrument, the Chicago Community Asthma Survey (CCAS)-32. Development began with two qualitative steps. First, a review of the published literature guided the initial instrument construction (Step 1). Content domains were chosen based on clinical input and the Health Belief Model. Most items were derived from existing instruments. To assess content validity, cognitive interviews and expert reviews were conducted (Step 2). Items were added, modified, and deleted based on the information gathered at each of these steps. In the next step, item performance measurement (Step 3), testing of two samples provided quantitative data to further inform item reduction. Items with uniform correct responses or responses lacking in variability were excluded. The result of this three-step process was a 32-item survey of asthma knowledge, attitudes and perceptions, the CCAS-32. The introduction to the survey was subsequently modified to minimize respondent bias (Step 4). In conclusion, the CCAS-32 was constructed with input from experts in asthma and individuals from the Chicago area. The items in the CCAS-32 appear to have both face validity and acceptable performance characteristics.

Adolescent↗

PubMed1999

The effects of asthma experience and social demographic characteristics on responses to the Chicago Community Asthma Survey-32. Chicago Asthma Surveillance Initiative Project Team.

INTRODUCTION: The Chicago Community Asthma Survey (CCAS-32) is an instrument for characterizing the general public's knowledge, attitudes, and beliefs related to asthma. The purpose of this study was to examine the effects of asthma experience and social demographic characteristics on asthma awareness among the general public. METHODS: The CCAS-32 consists of 21 dichotomous items, designed primarily to test asthma knowledge, and 11 Likert-scale items, focusing on asthma attitudes and beliefs. From December 1997 through February 1998, a random-digit dialing method was used to administer the CCAS-32 via a telephone survey of Chicago-area (seven-county) residents > or = 18 years. Each respondent's asthma experience was classified as "person with asthma," "family/household experience," or "no/low asthma experience." Demographic variables included sex, age, education, race/ethnicity, urban vs suburban residence, and income. RESULTS: Five hundred sixty-eight Chicago-area residents completed the survey (response rate of 40.6%). Of these, 43.3% were aged 35 to 64 years, 71.3% were women, 66.7% were white, and 71.3% had completed at least some college. Sixty-two percent had no or low asthma experience, 28.5% had family or household experience, and 9.5% were persons with asthma. The mean percentage (+/- SE) of correct, or desirable, responses to asthma knowledge questions was 71.9 +/- 0.5%, with a range from 31.9 to 95.1%. The mean percentage of desirable responses differed significantly between persons with no or low asthma experience, family or household asthma experience, and persons with asthma (70.0 +/- 0.6%, 74.0 +/- 0.9%, and 77.7 +/- 1.2%, respectively, p < 0.01 for trend). Social demographic factors also appeared to result in statistically significant differences in the responses to many items. Of the demographic variables studied, age and education appeared to have the strongest effect on responses to knowledge items, with statistically significant differences in responses seen for 10 (47.6%) and 8 (38.1%) of the 21 dichotomous items. Race or ethnicity and education were each associated with differences in responses for 7 of the 11 Likert-scale items (63%). CONCLUSIONS: The results of this study suggest that the CCAS-32 can detect meaningful differences between groups with different degrees of asthma experience (ie, discriminative validity). Using the CCAS-32, it may be possible to identify subpopulations with differences in asthma awareness, thus providing guidance for the design of messages to target community and public awareness of asthma.

Adolescent↗

PubMed1999

Confirmation of N-(nitrosomethyl) urea as a nitrosourea derived by nitrosation of fish sauce.

N-(nitrosomethyl) urea (NMU) was characterized in the carcinogenic nitrosated fish sauce (NFS) with high performance liquid chromatography (HPLC)-photohydrolysis-pyrolysis-thermal energy analysis recently. We used HPLC-electronic spray ionization-mass spectrometry and HPLC-diode array detection to confirm NMU in NFS further. It was observed that the corresponding chromatographic fraction of NMU of NFS showed the same mass spectrum (m/z 64, 102, and 145) and ultraviolet-absorbance (lambda max = 230 nm) as those of authentic NMU. These results confirmed that the component of NFS was NMU.

Carcinogens↗

PubMed1999

Mechanisms of beneficial effects of probucol in adriamycin cardiomyopathy.

Probucol, a lipid-lowering drug, has been shown to offer protection against adriamycin-induced cardiomyopathy. In order to define the mechanism of this protection, we examined changes in antioxidants and lipid peroxidation in hearts as well as lipids in hearts and plasma from rats treated with either adriamycin or adriamycin and probucol with appropriate controls. Any potential free radical quenching as well as growth inhibitory effects of probucol were also examined using Chinese hamster ovary (CHO) cells in culture. In animal model, adriamycin caused a significant depression in glutathione peroxidase and increased plasma and cardiac lipids as well as lipid peroxidation. Probucol treatment modulated adriamycin-induced cardiomyopathic changes and increased glutathione peroxidase and superoxide dismutase activities. In the presence of adriamycin under hypoxic conditions, formation of adriamycin semiquinone radical was detected by ESR. The cell growth in these cultures was also inhibited by adriamycin in a dose-dependent manner. Probucol had no effect on adriamycin-induced growth inhibition as well as formation of semiquinone radicals. It is proposed that probucol protection against adriamycin cardiomyopathy is mediated by increased antioxidants and lipid-lowering without any effect on free radical production.

Animals↗

PubMed1999

Retinal degeneration in tulp1-/- mice: vesicular accumulation in the interphotoreceptor matrix.

PURPOSE: The Tulp1 gene is a member of the tubby gene family with unknown function. Mutations in the human TULP1 gene cause autosomal recessive retinitis pigmentosa. To understand the pathogenic mechanism associated with TULP1 mutations and to explore the physiologic function of this protein, we examined tissue distribution of the Tulp1 protein in normal mice and the photoreceptor disease phenotype in Tulp1-ablated mice. METHODS: Tissue distribution of the Tulp1 protein in normal mice was examined by immunoblotting and immunocytochemistry. The disease phenotype in tulp1-/- mice was studied by light and electron microscopy, electroretinography (ERG), and immunocytochemistry. These results were compared with another mouse model of retinal degeneration carrying a rhodopsin mutation. RESULTS: Tulp1 is found exclusively in photoreceptors, localizing predominantly in the inner segments. It is a soluble protein with an apparent molecular weight of approximately 70 kDa. Photoreceptor degeneration developed in tulp1-/- mice, with early involvement of both rods and cones. At the early stage of degeneration, rod and cone opsins, but not peripherin/RDS, exhibited prominent ectopic localization. Electron microscopy revealed massive accumulation of extracellular vesicles surrounding the distal inner segments. CONCLUSIONS: The function of Tulp1 is required to maintain viability of rod and cone photoreceptors. Extracellular vesicular accumulation is not a common phenomenon associated with photoreceptor degeneration but appears to be a distinct ultrastructural feature shared by a small group of retinal disease models. The defect in tulp1-/- mice may be consistent with a loss of polarized transport of nascent opsin to the outer segments.

Animals↗