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L Hyman

Publications and source records attributed to L Hyman.

At least 19 recordsLinked to original sources
PubMed2001

Prevalence and causes of visual impairment in The Barbados Eye Study.

OBJECTIVE: To determine the prevalence and causes of low vision and blindness in a predominantly black population. DESIGN: Population-based prevalence study of a simple random sample of Barbados-born citizens aged 40 to 84 years. PARTICIPANTS: Four thousand seven hundred nine persons (84% participation). METHODS: The standardized protocol included best-corrected visual acuity (with a Ferris-Bailey chart), automated perimetry, lens gradings (LOCS II), and an interview. Participants with visual acuity of worse than 20/30, other positive findings, and a 10% sample also had an ophthalmologic examination that evaluated the cause and extent of vision loss (resulting from that cause), if any. MAIN OUTCOME MEASURES: Low vision and blindness were defined as visual acuity in the better eye between 6/18 and 6/120 and visual acuity worse than 6/120, respectively (World Health Organization [WHO] criteria). RESULTS: Of the 4631 participants with complete examinations, 4314 (93%) reported their race as black, 184 (4%) reported their race as mixed (black and white), and 133 (3%) reported their race as white or other. Low vision was found in 5.9% of the black, 2.7% of the mixed, and 3.0% of white or other participants. Bilateral blindness was similar for black and mixed race participants (1.7% and 1.6%, respectively) and was not found in whites. Among black and mixed participants, the prevalence of low vision increased with age (from 0.3% at 40-49 years to 26.8% at 80 years or older). The prevalence of blindness was higher (P < 0.001) for men than women at each age group (0.5% versus 0.3% at ages 40-49 and 10.9% versus 7.3% at 80 years or more). Sixty percent of blindness was due to open-angle glaucoma and age-related cataract, each accounting for more than one fourth of cases. Other major causes were optic atrophy or neuropathy and macular and other retinal diseases. Few cases of blindness were due to diabetic retinopathy (1.4%), and none were due to age-related macular degeneration. CONCLUSIONS: Using the WHO criteria, prevalence of visual impairment was high in this African-origin population, particularly at older ages. Most blindness was due to open-angle glaucoma and cataract, with open-angle glaucoma causing a higher proportion of blindness than previously reported. The increased prevalence of blindness in men may be due to the increased male prevalence of glaucoma in this population and warrants further investigation. Results underline the need for blindness prevention programs, with emphasis on effective treatment of age-related cataract and enhancing strategies for early detection and treatment of open-angle glaucoma.

Adult↗
PubMed2001

The Correction of Myopia Evaluation Trial (COMET): design and general baseline characteristics.

The Correction of Myopia Evaluation Trial (COMET) is a multicenter, randomized, double-masked, controlled clinical trial evaluating whether there is a difference in the progression of myopia between children wearing progressive addition lenses (PALs) versus conventional single vision lenses (SVLs), as measured by cycloplegic autorefraction. Axial length, measured by A-scan ultrasonography, is an additional outcome measure. To meet the recruitment goal of 450 participants, eligible children ages 6-11 years (inclusive) with myopia in both eyes (spherical equivalent between -1.25 diopters (D) and -4.50 D, astigmatism < or = 1.50 D, and anisometropia < 1.00 D) were recruited at four clinical centers between September 1997 and September 1998. Children who participated were assigned to receive PALs (Varilux Comfort with a +2.00 D addition) or SVLs. Measures include standardized cycloplegic autorefraction (Nidek ARK700A autorefractor), axial length (Sonomed A2500 ultrasound), subjective refraction (Marco TRS system), visual acuity (modified Early Treatment Diabetic Retinopathy Study protocol), accommodation (Canon R-1), and phoria (cover test and Maddox rod). Outcome measures are collected annually; adherence is assessed and prescriptions updated semiannually. Participants are being followed for at least 3 years. COMET enrolled 469 children. Their mean age is 9.3 years (range 6-11 years); 52% are female. COMET children are ethnically diverse, according to a self-report with 46% White, 26% African American, 14% Hispanic, and 8% Asian. Best-corrected visual acuity is better than 20/32 in both eyes. Baseline mean (+/-SD) cycloplegic refractive correction is -2.38 D (+/-0.81) in the right eye and -2.40 D (+/-0.82) in the left eye; mean (+/-SD) axial length is 24.1 mm (+/-0.7) in both eyes. Follow-up of these children will provide a first step in answering the important question of whether there are effective means to slow myopia progression. Study results should be applicable to a large proportion of children with myopia. The study will also provide useful information on myopia progression in children wearing conventional single vision lenses.

Child↗
PubMed2000

Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group.

OBJECTIVES: To describe a case-control study of risk factors for neovascular and non-neovascular age-related macular degeneration (AMD) and to present findings on associations with systemic hypertension and cardiovascular disease. METHODS: Participants with and without neovascular and non-neovascular AMD were recruited from 11 ophthalmology practices in the New York, NY, metropolitan area. Comprehensive data collection included (1) a standardized interview, (2) blood pressure measurements, and (3) blood samples. Cases and controls were classified from fundus photograph gradings. Polychotomous logistic regression analyses were used to evaluate associations. RESULTS: Classification of 1222 sets of available photographs resulted in the inclusion of a neovascular case group (n = 182), a non-neovascular case group (n = 227), and a control group (n = 235). Neovascular AMD was positively associated with diastolic blood pressure greater than 95 mm Hg (odds ratio [OR] = 4.4), self-reported use of potent antihypertensive medication (OR = 2.1), physician-reported history of hypertension (OR = 1.8), use of antihypertensive medication (OR = 2.5), combinations of self-reported and physician-reported data on hypertension and its treatment (OR = 1. 7), high-density lipoprotein level (OR = 2.3), and dietary cholesterol level (OR = 2.2). Non-neovascular AMD was unrelated to hypertension or cholesterol level. No associations were found between either AMD type and other definitions of hypertension or other cardiovascular disease. CONCLUSIONS: These findings suggest that neovascular AMD is associated with moderate to severe hypertension, particularly among patients receiving antihypertensive treatment. They also support the hypotheses that neovascular and non-neovascular AMD may have a different pathogenesis and that neovascular AMD and hypertensive disease may have a similar underlying systemic process.

Aged↗
PubMed2000

Author's reply

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Journal Article↗
PubMed1999

Diabetes, hypertension, and central obesity as cataract risk factors in a black population. The Barbados Eye Study.

OBJECTIVE: The increased cataract prevalence of black populations, especially of cortical cataract, remains unexplained. The authors evaluate the relationships of diabetes, hypertension, and obesity patterns to lens opacities, by age, among 4314 black participants in the Barbados Eye Study. DESIGN AND PARTICIPANTS: Prevalence study of a random sample of the Barbados population, ages 40 to 84 years (84% participation). MAIN OUTCOME MEASURES: Associations with age-related lens changes (grade > or = 2 in the Lens Opacities Classification System II at the slit lamp) were evaluated in logistic regression analyses by age (persons < 60 years and > or = 60 years). Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: Of the 1800 participants with lens changes, most had cortical opacities. Diabetes history (18% prevalence) was related to all lens changes, especially at younger ages (age < 60 years: OR = 2.23 [1.63, 3.04]; age > or = 60 years: OR = 1.63 [1.22, 2.17]). Diabetes also increased the risk of cortical opacities (age < 60 years: OR = 2.30 [1.63, 3.24]; age > or = 60 years: OR = 1.42 [1.03, 1.96]); additional risk factors were high diastolic blood pressure (age < 60 years: OR = 1.49 [1.00, 2.23]) and higher waist/hip ratio (all ages: OR = 1.36 [1.00, 1.84]). Diabetes was also related to posterior subcapsular opacities. Glycated hemoglobin levels were positively associated with cortical and posterior subcapsular opacities. Overall, 14% of the prevalence of lens changes could be attributed to diabetes. CONCLUSIONS: The high prevalence of cortical opacities was related to diabetes, hypertension, and abdominal obesity, which also are common in this and other black populations. Interventions to modify these risk factors, especially in populations in which they are highly prevalent, may have implications to control visual loss from cataract, which is the first cause of blindness worldwide.

Adult↗
PubMed1999

Diabetic retinopathy in a black population: the Barbados Eye Study.

OBJECTIVE: The distribution of diabetic retinopathy in black populations is largely unknown. The authors present retinopathy data from the predominately black participants of the Barbados Eye Study (BES). DESIGN AND PARTICIPANTS: Prevalence study of 4631 participants based on a random sample of the Barbados population 40 to 84 years of age (84% participation). MAIN OUTCOME MEASURES: Diabetes was defined as self-reported history of physician-diagnosed diabetes or glycosylated hemoglobin greater than 10% (>2 standard deviations above the population mean of persons without a diabetes history). Retinopathy was assessed by independent gradings of 30 degrees color stereo fundus photographs of the disc and macula. RESULTS: Diabetes was present in 19.4% of black (n = 4314), 15.2% of mixed (black and white; n = 184), and 7.5% of white/other (n = 133) self-reported racial groups. In the black/mixed population, regardless of diabetes status, the prevalence of retinopathy was 5.9%. In the 636 black and mixed participants with diabetes, the prevalence of retinopathy was 28.5%: 19.8% had minimum changes, 7.7% had moderate changes, and 0.9% had severe retinopathy. Clinically significant macular edema (CSME) was found in 8.6% of those with diabetes. CONCLUSIONS: In the population of African origin, approximately 1 in 17 persons had retinopathy. Among those with diabetes, 28.5% had retinopathy and 8.6% had CSME. These results highlight the clinical and public health relevance of diabetic retinopathy in the black population.

Adult↗
PubMed1999

Early Manifest Glaucoma Trial: design and baseline data.

OBJECTIVES: The Early Manifest Glaucoma Trial (EMGT) will evaluate the effectiveness of reducing intraocular pressure (IOP) in early, previously untreated open-angle glaucoma. Its secondary aims are to explore factors related to glaucoma progression and to study the natural history of the disease. This article describes the EMGT design and presents baseline data. DESIGN: Randomized, clinical trial. PARTICIPANTS: Newly diagnosed patients 50 to 80 years of age with early glaucomatous visual field defects were mainly identified from a population-based screening of more than 44,000 residents of Malmö and Helsingborg, Sweden. Exclusion criteria were advanced visual field loss; mean IOP greater than 30 mmHg or any IOP greater than 35 mmHg; visual acuity less than 0.5; and inability to complete follow-up protocols. INTERVENTIONS: After informed consent, patients were randomized to treatment or no initial treatment with close follow-up. Treated patients had laser trabeculoplasty and started receiving topical betaxolol twice daily in eligible eyes. Follow-up visits include computerized perimetry and tonometry every 3 months and fundus photography every 6 months. Decisions to change or begin treatment are made jointly with the patient when EMGT progression occurs and also later if clinically needed. MAIN OUTCOME MEASURES: The EMGT progression is defined by sustained increases of visual field loss in three consecutive C30-2 Humphrey tests, as determined from computer-based analyses, or by optic disc changes, as determined from flicker chronoscopy and side-by-side comparisons of fundus photographs performed by masked, independent graders. RESULTS: A total of 255 patients were randomized between 1993 and 1997 and will be followed for at least 4 years. All had generally good health status; mean age was 68.1 years, and 66% were women. At baseline, mean IOP was 20.6 mmHg and 80% of eyes had IOP less than 25 mmHg. CONCLUSIONS: The Early Manifest Glaucoma Trial is the first large randomized, clinical trial to evaluate the role of immediate pressure reduction, as compared to no initial reduction, in patients with early glaucoma and normal or moderately elevated IOP. Its results will have implications for: (1) the clinical management of glaucoma; (2) understanding the role of IOP and the natural history of glaucoma; and (3) evaluating the rationale for glaucoma screening.

Adrenergic beta-Antagonists↗
PubMed1999

Frequency of convergence insufficiency among fifth and sixth graders. The Convergence Insufficiency and Reading Study (CIRS) group.

PURPOSE: To estimate the frequency of convergence insufficiency (CI) and its related clinical characteristics among 9- to 13-year-old children. METHODS: Fifth and sixth graders were screened in school settings at three different study sites. Eligible children with 20/30 or better visual acuity, minimal refractive error, no strabismus, and exophoria at near were evaluated according to a standardized protocol to determine the presence and severity of CI. These children were classified according to the presence and number of the following clinical signs: (1) exophoria at near > or =4delta than far, (2) insufficient fusional convergence, and (3) receded nearpoint of convergence. Also, children were classified as accommodative insufficient (AI) if they failed Hofstetter's minimum amplitude formula or had greater than a + 1.00 D lag on Monocular Estimate Method retinoscopy. RESULTS: Of 684 children screened, 468 (68%) were eligible for further evaluation. Of these, 453 had complete data on CI measurements and were classified as: no CI (nonexophoric at near or exophoric at near and < 4delta difference between near and far) (78.6%); low suspect CI (exophoric at near and one clinical sign: exophoria at near > or =4delta than far) (8.4%); high suspect CI (exophoric at near and two clinical signs) (8.8%); and definite CI (exophoric at near and three clinical signs) (4.2%). CI status varied according to ethnicity and study site (p < 0.0005), but not gender. The frequency of AI increased with the number of CI-related signs. For CI children with three signs, 78.9% were classified as also having AI. CONCLUSIONS: These findings suggest that CI (defined as high suspect and definite) is frequent (13%) among fifth and sixth grade children. In addition, there is a high percentage of CI children with an associated AI.

Accommodation, Ocular↗
PubMed1999

Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.

Formation of mRNA 3' ends in eukaryotes requires the interaction of transacting factors with cis-acting signal elements on the RNA precursor by two distinct mechanisms, one for the cleavage of most replication-dependent histone transcripts and the other for cleavage and polyadenylation of the majority of eukaryotic mRNAs. Most of the basic factors have now been identified, as well as some of the key protein-protein and RNA-protein interactions. This processing can be regulated by changing the levels or activity of basic factors or by using activators and repressors, many of which are components of the splicing machinery. These regulatory mechanisms act during differentiation, progression through the cell cycle, or viral infections. Recent findings suggest that the association of cleavage/polyadenylation factors with the transcriptional complex via the carboxyl-terminal domain of the RNA polymerase II (Pol II) large subunit is the means by which the cell restricts polyadenylation to Pol II transcripts. The processing of 3' ends is also important for transcription termination downstream of cleavage sites and for assembly of an export-competent mRNA. The progress of the last few years points to a remarkable coordination and cooperativity in the steps leading to the appearance of translatable mRNA in the cytoplasm.

Alternative Splicing↗
PubMed1998

Individual change after genocide in Bosnian survivors of "ethnic cleansing": assessing personality dysfunction.

The authors used the SCID-DES (disorders of extreme stress) instrument to assess for personality change in Bosnian survivors of "ethnic cleansing." Twenty four refugees underwent systematic, trauma-focused, research assessments, including the SCID-DES interview. Overall, this group of Bosnian survivors had been severely traumatized as a result of the Serbian nationalists' genocide. However, no subject met diagnostic criteria for DES. The SCID-DES yields far lower rates of trauma-related personality change in Bosnian survivors of genocide than in adult survivors of prolonged early life traumas. Therefore, the DES construct may have better application to prolonged, interpersonal, early life traumas than to the prolonged, communal traumas of genocide.

Adolescent↗
PubMed1998

Frequency of convergence insufficiency in optometry clinic settings. Convergence Insufficiency and Reading Study (CIRS) Group.

PURPOSE: To estimate the frequency of convergence insufficiency (Cl) and its related characteristics among 8- to 12-year-old children randomly selected from 2 optometry clinic populations. METHODS: Clinic records of 620 children were randomly selected and reviewed according to a standard protocol, using a systematic sampling method based on the total number of 8- to 12-year-old children seen over a 1-year period at 2 optometry clinics. Records were reviewed for demographic and clinical data. Data on Cl-related symptoms were obtained at one of the sites. Records that met the eligibility criteria of: good visual acuity (20/30 or better in both eyes); minimal refractive error (-0.50 to +1.00 D and < or = 1.00 D of astigmatism in either eye, and < or = 1.00 D of anisometropia); and no strabismus were evaluated for Cl-related characteristics. Eligible children were classified according to the direction of their near heterophoria and the number of the following clinical signs present: (1) exophoria at near > or = 4 delta than at far; (2) insufficient fusional convergence [i.e., failing Sheard's criterion or minimum normative positive fusional vergence (PFV) of 12 delta base-out (BO) blur/15 delta BO break]; and (3) receded nearpoint of convergence (NPC) of > or = 7.5 cm break or > or = 10.5 cm recovery. Children were then classified as: no Cl (nonexophoric at near or < 4 delta difference between far and near); low suspect (exophoric at near and 1 sign); high suspect (exophoric at near and 2 signs); or definite Cl (exophoric at near and 3 signs). RESULTS: Sixty-seven percent (415/620) of the records met the eligibility criteria and had complete data on phoria, NPC, and PFV. The age (mean +/- SD) of the study population was 10.2 +/- 1.2 years. Ethnicity data were available for 85% of those eligible; the ethnic distribution was 36% African American, 29% Caucasian, 19% Hispanic, and 1% Asian. About one-half of the 415 children were classified as either low suspect (33%); high suspect (12%); or definite Cl (6%). Clinically significant Cl (high suspect and definite categories) was identified in 17.6% of the children. The percentage of children rated as symptomatic increased with the number of Cl-related clinical signs present. CONCLUSIONS: These findings suggest a high frequency of Cl in optometry clinic populations and a potential correlation between patient symptoms and the number of Cl signs present.

Child↗
PubMed1998

PTSD symptoms in Bosnian refugees 1 year after resettlement in the United States.

OBJECTIVE: The authors' goal was to describe the characteristics of posttraumatic stress disorder (PTSD) symptoms on resettlement in the United States and at 1-year follow-up among Bosnian refugees as well as possible factors affecting the PTSD symptom profile among these refugees. METHOD: They used standardized instruments to assess 34 Bosnian refugees for PTSD at resettlement in the United States and 1 year later. RESULTS: Fifteen of the refugees were diagnosed with PTSD at 1-year follow-up, compared with 25 at initial assessment. The average PTSD severity score at follow-up was 12.5, compared with 20.6 at initial assessment. At 1-year follow-up, 25 of the refugees experienced a decrease in severity of PTSD symptoms, one remained the same, and eight experienced an increase in severity. Older refugees were significantly more likely to have PTSD than younger refugees, and older refugees had more severe symptoms. CONCLUSIONS: The level of PTSD diagnosis and symptoms in Bosnian refugees remained substantial 1 year after their resettlement in the United States, although there were notable overall decreases. Older refugees appeared to be at greater risk.

Adolescent↗
PubMed1997

Prevalence of lens opacities in the Barbados Eye Study.

OBJECTIVE: To present population-based data on type and extent of age-related lens opacities in the predominantly black population of the Barbados Eye Study. DESIGN: Prevalence study. SETTING AND PARTICIPANTS: The Barbados Eye Study included 4709 participants (84% of those eligible), who were identified from a random sample of Barbadian-born citizens aged 40 to 84 years. DATA COLLECTION: Lens gradings at the slit lamp, obtained with the use of the Lens Opacities Classification System II. MAIN OUTCOME MEASURE: Prevalence of posterior subcapsular, nuclear, and cortical opacities (defined as a grade > or = 2 in either eye), as well as prevalence of any lens changes (including history of previous cataract surgery and/or cataract too advanced to grade). RESULTS: Overall, 41% of the Barbados Eye Study population had any lens changes, including 3% with aphakia or an intraocular lens. Among the population of African descent, cortical opacities (34%) were most prevalent, followed by nuclear (19%) and posterior subcapsular (4%) opacities. Prevalence of all opacity types increased with age (P < .001). Cortical and nuclear opacities were more frequent in women than men. When prevalence of a single kind of opacity was considered, 21% of participants had cortical only, 6% had nuclear only, and 0.4% had posterior subcapsular only; 13% had mixed opacities. Visual acuity loss to worse than 20/40 in the more affected eye was present in 48%, 26%, and 18% of nuclear only, posterior subcapsular only, and cortical only types, respectively, and in 53% of mixed opacities. CONCLUSIONS: The Barbados Eye Study provides the first prevalence data on different types of lens opacities in a large, predominantly black population. Whereas nuclear opacities are most common in white populations, cortical opacities were the most frequent type in the Barbados Eye Study, a finding of possible etiologic relevance. Other results highlight a higher frequency of opacities in women than men and a high prevalence of visual acuity loss in affected eyes.

Adult↗
PubMed1997

Distribution of intraocular pressure. The Barbados Eye Study.

OBJECTIVE: To provide data on the distribution of intraocular pressure (IOP) in a predominantly black population, which has a high prevalence of open-angle glaucoma. DESIGN: Population-based prevalence study. SETTING AND PARTICIPANTS: Participants (N = 4601) (age range, 40-84 years) who had undergone applanation tonometry measurements in the Barbados Eye Study. Self-reported race was 93% black, 4% mixed (black and white), and 3% white or other. DATA COLLECTION: A standardized protocol included applanation tonometry and other ocular measurements, fundus photography, demographic data, and an interview. MAIN OUTCOME MEASURES: The average of 3 IOP measurements at the Barbados Eye Study visit was used to compare IOP by self-reported race. Descriptive data on IOP by age, sex, glaucoma status, and cup-disc ratio were examined in the black population. RESULTS: The IOP was highest in the population of African origin. The mean (+/-SD) IOP values for black, mixed, and white participants were 18.7 +/- 5.2, 18.2 +/- 3.8, and 16.5 +/- 3.0 mm Hg, respectively. An IOP greater than 21 mm Hg was present in 18.4%, 13.6%, and 4.6% of the black, mixed, and white participants, respectively. In analyses that were adjusted for age, sex, and glaucoma status, such values were 5 times as likely in black than white participants and 3.5 times as likely in mixed race participants (P < .01). Among the black participants, the mean IOP increased approximately 1 mm Hg for every increase in 10 years of age. After excluding persons with any type of glaucoma, suspected glaucoma, or a history of glaucoma treatment, women had significantly (P < .01) higher IOP values; however, no significant IOP trends by sex were evident in the group with glaucoma. The IOP was also positively associated (P < .05) with vertical cup-disc ratios. After 2 visits, the IOP remained 21 mm Hg or less in 21% of the persons with glaucoma vs 64% of those without glaucoma. CONCLUSIONS: In the black participants, the IOP was higher than in the white participants. The IOP was also associated with age and cup-disc ratios. The results showed that open-angle glaucoma and a high IOP alone have a different distribution by sex; although open-angle glaucoma was more frequent in men, ocular hypertension was more frequent in women. These data have implications for the detection and causation of open-angle glaucoma in this high-risk population.

Adult↗
PubMed1997

A family survives genocide.

This is a case study of a family that survived genocide and a discussion of families and massive psychic trauma. This family, like many others from Bosnia-Herzegovina, was driven from their home by Serb forces-"ethnically cleansed"-then eventually escaped to Croatia, and was later resettled in the United States. They were referred to us, a group of mental health professionals who established the Bosnian Refugee Trauma Program at the Yale Psychiatric Institute (YPI). We have done clinical, testimony, and research work with the refugee families from Bosnia who resettled in our region, described in part in prior reports (Weine, Becker et al. 1995a, 1995b; Weine and Laub 1995).

Adolescent↗
PubMed1997

Lens opacities, demographic factors and nutritional supplements in the Barbados Eye Study.

BACKGROUND: This study evaluated the association of age-related lens opacities with the use of nutritional supplements and demographic factors among 4314 black participants (> or = 40 years) in the population-based Barbados Eye Study. METHODS: Lenses were classified at the slit lamp by the Lens Opacities Classification System II (LOCS II); a score > or = 2 was used to define the presence of gradable lens opacities, by type. Lens changes also included prior cataract surgery or cataract too advanced to grade. Associations with risk factors were evaluated by logistic regression analyses. RESULTS: The study identified 1800 individuals with lens changes in at least one eye; 229 had nuclear opacities only; 851 had cortical opacities only. Older age and indicators of lower socioeconomic status (low education and/or non-professional occupation), were positively associated with both nuclear (odds ratio [OR] = 1.90) and cortical (OR = 1.47) opacities. Women had an increased risk of cortical opacities (OR = 1.41). Regular users of nutritional supplements were less likely to have lens changes (OR = 0.78) and, specifically, cortical opacities (OR = 0.77). The association with nutritional supplements was present in those < 70 years, but not at older ages. CONCLUSIONS: The study supports the association of lower socioeconomic status with lens changes, including nuclear and cortical lens opacities. The findings also suggest that regular users of nutritional supplements have a one-fourth lower risk of lens changes and particularly, of cortical opacities; a result seen at ages under 70 years. The associations with potentially modifiable factors indicate the need for further evaluations, given the high prevalence of lens opacities.

Adult↗
PubMed1996

High mobility group protein 14 and 17 can prevent the close packing of nucleosomes by increasing the strength of protein contacts in the linker DNA.

High mobility group (HMG) proteins 14 and 17 are abundant chromatin-associated proteins found in all higher eukaryotic nuclei. This observation demonstrates that HMGs 14 and 17 must have an important and universal function with regard to the structure and function of chromatin. What this function is, including how they interact with a nucleosomal array in vivo, is not known. Recently, we have demonstrated that HMGs 14 and 17 can organize nucleosomes into a regular array and increase the repeat length from 145 to about 160-165 base pairs in vitro. In addition, they can increase the apparent repeat length of chromatin deficient in histones H2A/H2B from 125 to approximately 145 base pairs. Importantly, this template was transcriptionally active. In this study, we report five new observations that begin to address the mechanism by which HMGs 14 and 17 space nucleosomal particles. First, we demonstrate that both human placenta HMG 14 and HMG 17 can space nucleosomes to produce a chromatin template with a repeat length around 160 base pairs. This result further highlights the similarity between these proteins in terms of protein structure and perhaps function. Second, we show that digestion of HMG containing chromatin with micrococcal nuclease produces DNA fragments that were approximately 10 and 20 base pairs longer than nucleosome core-particle DNA. This suggests that HMG 14 or HMG 17 can protect, directly or indirectly, at least an additional 10 base pairs of linker DNA from micrococcal digestion. However, this HMG-containing particle does not produce a strong kinetic block, and further digestion results in the eventual accumulation of DNA fragments 145 base pairs in length. Third, by comparing the full-length protein with different domains, we demonstrate that the acidic carboxyl-terminal domain is absolutely required for nucleosome spacing, neither the nucleosome binding domain of HMG 14 or HMG 17 nor the amino-terminal domain plus the nucleosome binding domain of HMG 14 could space nucleosomes. Fourth, we demonstrate that extensive micrococcal nuclease digestion of chromatin deficient in histones H2A/H2B led to the accumulation of DNA fragments about 110 base pairs in length, which is presumably the length of DNA associated with a nucleosomal particle deficient in one H2A/H2B dimer. Incorporation of either HMG 14 or HMG 17 into this chromatin results in the disappearance of this band and increase in the accumulation of fragments around 140-150 base pairs in length. Finally, in contrast to spacing of complete nucleosomes, we find that the nucleosome binding domain of HMG 17 (but not the nucleosome binding of HMG 14) is the only domain required for spacing of H2A/H2B-deficient chromatin.

Animals↗