Biomedical subjects

J Skurnick

Publications and source records attributed to J Skurnick.

At least 19 recordsLinked to original sources

PubMed2006

Mortality in African-Americans with Type 1 diabetes: The New Jersey 725.

AIM: To determine rates and risk factors for all-cause mortality in African-Americans with Type 1 diabetes from a 3-year observational follow-up study of 725 African-Americans with Type 1 diabetes conducted between 1 January 1999 and 31 December 2001. METHODS: Date of death was ascertained either from telephone contact with the patient's family or from relatives or on line review of the US Social Security death index. RESULTS: Since the initial examination, 131 (18.1%) patients, 60 (20%) men and 71 (17%) women, have died. At the time of death, the mean age of the men was 40.7 +/- 10.6 years and that of the women 39.4 +/- 10.5 years. The median duration of diabetes at the baseline examination was 8.04 years, interquartile range (IQR) 3.76-15.22 years for men and median 10.54, IQR 4.49-18.36 years for women. Three-year mortality rates were 7.1% for women and 10.6% for men. Age-adjusted mortality rates were not significantly different between men and women. Relative to the general US and the New Jersey African-American population, standardized mortality ratios of African-Americans with Type 1 diabetes were 12 and six times greater for women and men, respectively. Older age, low socio-economic status, low body mass index, high diastolic blood pressure, macroangiopathy, proteinuria, severe diabetic retinopathy and heavy alcohol consumption were independent risk factors for all-cause mortality. In patients with microproteinuria at initial examination, the mortality rate for men was twice that of women. CONCLUSION: Microproteinuria and other potentially modifiable factors, including hypertension, macroangiopathy and heavy alcohol consumption, are independent risk factors for mortality in this ethnic group.

Adult↗

PubMed2004

Age-dependent telomere attrition as a potential indicator of racial differences in renal growth patterns.

BACKGROUND: Racial differences in the predilection to salt sensitivity may arise from different renal growth patterns. To test this idea, we monitored age-dependent telomere attrition rate, reflecting largely the replicative history of somatic cells, in the outer renal cortex and the inner renal medulla of African Americans and Caucasians. METHODS: Telomere length, determined by the mean length of the terminal restriction fragments (TRF), was measured in specimens from 58 African-American and 63 Caucasian males, ages 1 day to 71 years. RESULTS: In the outer renal cortex, TRF length attrition rate was significantly slower in African Americans (-0.021 +/- 0.0064 kb/year) than in Caucasians (-0.060 +/- 0.0094 kb/year) (p = 0.0007). In both ethnic groups the TRF length attrition rate was slower in the inner medulla than in the outer renal cortex, but without significant racial differences. CONCLUSIONS: The proximal tubule is the most abundant nephron structure in the outer renal cortex. Less proliferative growth of proximal tubular cells in kidneys from African Americans may be one factor explaining the slower age-dependent telomere attrition rate in the outer renal cortex of African Americans than in Caucasians.

Adolescent↗

PubMed2001

Factors associated with age at natural menopause in a multiethnic sample of midlife women.

An unprecedented number of women will experience menopause in the next decade. Although the timing of menopause affects long-term disease risk, little is known about factors that affect this timing. In the present 1995--1997 cross-sectional study, the Study of Women's Health Across the Nation, the relation of demographic and lifestyle factors to age at natural menopause was examined in seven US centers and five racial/ethnic groups. All characteristics were self-reported by women aged 40--55 years (n = 14,620). Cox proportional hazards models were used to estimate the probability of menopause by age. Overall, median age at natural menopause was 51.4 years, after adjustment for smoking, education, marital status, history of heart disease, parity, race/ethnicity, employment, and prior use of oral contraceptives. Current smoking, lower educational attainment, being separated/widowed/divorced, nonemployment, and history of heart disease were all independently associated with earlier natural menopause, while parity, prior use of oral contraceptives, and Japanese race/ethnicity were associated with later age at natural menopause. This sample is one of the largest and most diverse ever studied, and comprehensive statistical methods were used to assess factors associated with age at natural menopause. Thus, this study provides important insights into this determinant of long-term disease risk in women.

Adult↗

PubMed2001

Age dependent aneuploidy and telomere length of the human vascular endothelium.

RATIONALE: Aneuploidy and telomere length are two major parameters that have been associated with cellular senescence in vitro. In order to explore the role of aneuploidy and telomere length in aging of the human vasculature, we studied these two parameters in direct preparations of endothelial cells of the human abdominal aorta. METHODS: Using fluorescent in situ hybridization on 'touch prep' slides, we evaluated aneuploidy of two autosomes (chromosomes 6 and 16) and sex chromosomes in non cultured endothelial cells of the abdominal aorta as a function of the donor's age. RESULTS: We found that the frequency of aneuploidy of vascular endothelial cells significantly increased with age. This was expressed by age-dependent tetrasomy (r(s)=0.56, P=0.006 for chromosome 6; and r(s)=0.54, P=0.008 for chromosome 16), and age dependent loss of the Y chromosome (r(s)=0.85, P=0.0003). In addition, we found that telomere length was inversely correlated with age (r=-0.38, P=0.008). DATA INTERPRETATION: These findings suggest that indicators of cellular senescence, earlier observed in vitro, are also expressed in the human vascular endothelium in vivo. Aneuploidy and telomere attrition might thus play a role in the aging of the human vasculature.

Adolescent↗

PubMed2001

Human papillomavirus typing in HIV-positive women.

OBJECTIVE: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), which were predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low-and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear. STUDY DESIGN: HPV DNA typing (low- and high-risk) by Digene (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis. RESULTS: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears which were read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes. CONCLUSION: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.

DNA, Viral↗

PubMed2001

Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity.

Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56+/-11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67+/-0.09 versus 8.37+/-0.07 kb; P=0.016). In both genders, telomere length was inversely correlated with age (P<0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.

Age Factors↗

PubMed2000

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis.

Little is known about the turnover rate (i.e. the rate of replication and death) of cells in the intima and media of human arteries as a function of age and atherosclerosis. One indicator of the replicative history of cells is telomere length. In this work we explored the rate of telomere attrition as a function of age and atherosclerosis in cells of the human abdominal aorta. Telomere length, measured by the terminal restriction fragment using Southern analysis, was determined in the intima and media of the distal (infrarenal) versus proximal (suprarenal) segments of the abdominal aorta. Telomere length was then correlated with age and atherosclerotic grade. The rate of age-dependent telomere attrition was higher in both the intima and media of the distal versus proximal abdominal aorta. In addition, telomere length was negatively correlated with atherosclerotic grade. However, after adjustment for age, this relationship was not statistically significant. The high rate of age-dependent telomere attrition in the distal abdominal aorta probably reflects enhanced cellular turnover rate due to local factors such as an increase in shear wall stress in this vascular segment.

Adolescent↗

PubMed2000

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Adult↗

PubMed1999

Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response.

Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8(+)-cell noncytotoxic inhibition of HIV replication in acutely infected CD4(+) cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8(+)-cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 Delta32 mutation in this population, nor did CD4(+) cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8(+)-cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.

Adult↗

PubMed1998

Synchrony in telomere length of the human fetus.

Telomere length, measured by terminal restriction fragments, was examined in tissues from human fetuses of gestational ages estimated as 15-19 weeks. The length of telomeres was similar in most fetal tissues. However, there were significant variations in telomere length among fetuses, with no apparent relationship between gestational age and telomere length. We conclude that synchrony in telomere length exists among tissues of the human fetus. This synchrony is apparently lost during extrauterine life.

Body Weights and Measures↗

PubMed1998

Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women.

OBJECTIVE: Our aim was to determine the effect of aging on the hypothalamic-pituitary-gonadal axis function. STUDY DESIGN: We studied 9 women aged 25 to 40 years with well-defined idiopathic premature ovarian failure and compared them with 8 women aged 51 to 70 years who had age-appropriate menopause. All women underwent 24 hours of frequent blood sampling every 10 minutes before and after replacement with transdermal estradiol targeted to achieve serum concentrations of approximately 100 pg/ml. RESULTS: In the absence of estrogen exposure, women with premature ovarian failure demonstrated a greater 24-hour mean luteinizing hormone concentration compared with that in the older women with age-appropriate menopause (32.3+/-4.3 mlU/ml vs 19.2+/-2.4 mlU/ml, p=0.0001). Despite the lesser luteinizing hormone serum levels in the older group, the luteinizing hormone pulse frequency per 24 hours was similar (22.1+/-3.0 pulses per 24 hours in prematurely menopausal women vs 21.9+/-2.5 pulses per 24 hours in the older postmenopausal women, p=0.94). When exposed to estrogen, mean luteinizing hormone concentrations decreased to 11.6+/-2.7 mlU/ml in prematurely menopausal women versus 4.4+/-1.0 mlU/ml in older postmenopausal women, p=0.017. Both groups had suppressed mean luteinizing hormone secretion compared with their paired, non-estradiol-exposed studies, p=0.0001. Frequency of luteinizing hormone pulsations was reduced to 16.5+/-3.5 pulses per 24 hours in prematurely menopausal women exposed to estradiol (p < 0.0058, compared with non-estradiol-exposed women). Further reduction was observed in older postmenopausal women (11.5+/-1.1 pulses per 24 hours, p=0.0001, compared with nonestradiol exposure, and p=0.0125, vs prematurely menopausal, estradiol-exposed women). Pulse amplitude was suppressed in both prematurely menopausal women (5.6+/-0.5 mlU/ml to 2.3+/-0.5 mlU/ml, p=0.0001) and older postmenopausal women (3.6+/-0.4 mlU/ml to 2.3+/-0.6 mlU/ml p=0.04) in the presence of estradiol. Although luteinizing hormone pulse amplitudes were greater in the women with premature menopause in the absence of estradiol (p=0.0028) compared with those in older postmenopausal women, pulse amplitudes became similar in the presence of estradiol. Parallel changes in mean follicle-stimulating hormone were observed. Women with premature ovarian failure had a mean follicle-stimulating hormone level of 71.1+/-9.4 mlU/ml that was suppressed to 18.0+/-4.1 mlU/ml after estradiol exposure (p=0.0001); values in older postmenopausal women were 45.9+/-6.0 and 10.3+/-2.0, respectively (p=0.0001). Although the women with premature ovarian failure secreted more follicle-stimulating hormone in the absence and presence of estradiol, only the former situation was statistically significant (p=0.0008 and p=0.23, respectively). CONCLUSIONS: These data suggest that there is an age-related decrease in gonadotropin secretion that may be hypothalamic or pituitary in origin. There is less luteinizing hormone secreted in women older than age 50. There is greater suppression of luteinizing hormone and follicle-stimulating hormone secretion by estradiol in aged women. Thus these data indicate that postmenopausal hormone changes involve central hypothalamic-pituitary alterations, as well as ovarian changes.

Adult↗

PubMed1998

HLA antigens associated with susceptibility/resistance to HIV-1 infection.

We studied the distribution of HLA-A, B, C, DR and DQ antigens in a cohort of HIV-1+ individuals and their heterosexual HIV seropositive (concordant) or seronegative (discordant) partners of Black non-Hispanic, Hispanic or Caucasian non-Hispanic ethnicity. The prevalence of DQ7 and Cw7 was significantly higher in the HIV-1+ compared to seronegative Black and Hispanic individuals, respectively. The frequency of DQ4 was significantly elevated in the Black seronegatives, whereas B53 was increased in the Hispanic seronegatives in comparison to the seropositives. No significant differences were observed between the Caucasian HIV infected and non-infected individuals. Analysis of the primary concordant HIV+ and discordant HIV+ individuals showed a marked increase in the prevalence of B44 in the Hispanic discordant seropositives, whereas the Caucasian primary concordants had a marked increase in the prevalence of A26. The prevalence of DQ7 and Cw7 was significantly increased in the Black and Hispanic secondary concordant seropositives, respectively in comparison to the seronegatives. The proportion of couples with matching HLA antigens was similar among the HIV-1+ concordant and discordant groups. These results provide additional evidence that HLA polymorphism may confer a genetic risk or protection for HIV-1 infection in individuals of various ethnic backgrounds.

Alleles↗

PubMed1998

Ca2+ in the dense tubules: a model of platelet Ca2+ load.

In this work, we explored the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (Vmax) of the SERCA significantly correlated with FECa2+ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the Vmax of the SERCA (r=.462, P=.010) and the FECa2+ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca2+ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca2+ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca2+ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa2+ in the DT, and (2) a higher BP is associated with an increase in platelet Ca2+ load in human beings, expressed by a rise in the FECa2+ in the DT and the upregulation of SERCA activity.

Adult↗

PubMed1998

Parameters of lymphocyte Na+-Ca2+ regulation and blood pressure: the gender effect.

Alterations in cellular Ca2+ and Na+ regulation play a role in the pathogenesis of essential hypertension. Using peripheral lymphocytes from 68 normal persons, we observed the following relationships for major cellular Ca2+ regulatory parameters. Among men and women, Na+-Ca2+ exchanger activity was positively correlated with the resting cytosolic free Ca2+ ([Ca2+]c) (r=0.43, P=0.0003), and the resting [Ca2+]c was positively correlated with cytosolic Na+ ([Na+]c) (r=0.50, P=0.0001). For men only, store-operated Ca2+ entry was positively correlated with Na+-Ca2+ exchanger activity (r=0.63, P=0.0001). In addition, systolic and diastolic blood pressures were positively correlated with [Na+]c in men (r=0.53, P=0.001, and r=0. 41, P=0.017, respectively) but not in women (r=0.30, P=0.088, and r=0.24, P=0.17, respectively). Some of the relationships between cellular and blood pressure parameters were confounded by serum triglycerides. These observations indicate a gender effect on cellular Ca2+-Na+ regulation and its relationship with blood pressure.

Adult↗

PubMed1998

Shortened telomere length in white blood cells of patients with IDDM.

IDDM is a polygenic and autoimmune disorder in which subsets of white blood cells (WBCs) are engaged in the destruction of beta-cells of the pancreas. The mechanisms that account for the abnormal behavior of these cells in IDDM are not fully understood. By measuring the mean length of telomeres of WBCs from patients with IDDM, we tested the concept that telomeres might play a role in IDDM. We examined the lengths of the terminal restriction fragments (TRFs) of DNA of WBCs from 234 white men comprising 54 patients with IDDM, 74 patients with NIDDM, and 106 control subjects. When adjusted for age, the TRF length from WBCs of patients with IDDM was significantly shorter than that of nondiabetic control subjects (mean +/- SE: 8.6 +/- 0.1 vs. 9.2 +/- 0.1, P = 0.002). No significant difference was observed between the TRF length from WBCs of patients with NIDDM versus nondiabetic subjects. Neither the duration nor the complications of IDDM (i.e., nephropathy and hypertension) had an effect on the TRF length of WBCs from patients with IDDM. The shortened TRF length of WBCs of patients with IDDM likely reflects a marked reduction in the TRF length of subsets of WBCs that play a role in the pathogenesis of IDDM.

Adolescent↗

PubMed1996

Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure.

Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8+ lymphocytes had greater anti-HIV-1 activity than did CD8+ lymphocytes from nonexposed controls. Further studies indicated that their purified CD4+ lymphocytes were less susceptible to infection with multiple primary isolates of HIV-1 than were CD4+ lymphocytes from the nonexposed controls. This relative resistance to HIV-1 infection did not extend to T-cell line-adapted strains, was restricted by the envelope glycoprotein, was not explained by the cell surface density of CD4 molecules, but was associated with the activity of the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. This relative resistance of CD4+ lymphocytes may contribute to protection from HIV-1 in multiply exposed persons.

CD4-Positive T-Lymphocytes↗

PubMed1995

PCR analysis of HIV-seronegative, heterosexual partners of HIV-infected individuals.

A cohort of human immunodeficiency virus (HIV)-discordant couples was established to evaluate risk factors associated with heterosexual viral transmission. Polymerase chain reaction (PCR) was utilized to document the HIV-uninfected status among members of discordant heterosexual couples and to rule out immunosilent infection. HIV DNA PCR specific for a gag gene region was performed on peripheral blood mononuclear cell samples from 203 HIV antibody-negative adults who have long-term heterosexual relationships with HIV-infected partners. The results were negative for 200 but consistently positive in three individuals. More extensive evaluation of these three individuals with an additional primer pair specific for the envelope gene, quantitative DNA PCR, multiple additional time points, and variable nucleotide tandem repeat analyses revealed specimen processing problems in two cases but an apparent true positive PCR assay in the third case. This subject remains antibody and PCR negative for a 32-month follow-up period. These results confirm previous studies that document a negligible incidence of occult HIV infection as delineated by PCR in antibody negative heterosexual partners of HIV-infected individuals. Specimen processing errors occur at a low rate (1% in this study) and require careful evaluation. The possibility of transient, aborted infection versus successful infection with a long immunosilent period was observed in a single individual. Definitive resolution of infection status will require long-term evaluation.

Adult↗

PubMed1993

Psychological distress, drug and alcohol use as correlates of condom use in HIV-serodiscordant heterosexual couples.

OBJECTIVE: To investigate the relationship between psychological distress, alcohol, drug and condom use in HIV-serodiscordant heterosexual couples. METHODS: Structured interviews were conducted to collect demographic information, detailed data on psychological distress, drug and alcohol use and sexual behavior. RESULTS: Analyses were based on 106 pairs of sexually active discordant couples. Significant differences among heterosexual condom users and non-users varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use and combining sex with drugs or alcohol. Employment was strongly associated with condom use in HIV-negative women whose regular sexual partners were HIV-positive men. CONCLUSION: The risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research on the effect of employment of HIV-negative women is required.

Adolescent↗