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Biomedical subjects

L Kuller

Publications and source records attributed to L Kuller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mucosal antibody expression following rapid SIV(Mne) dissemination in intrarectally infected Macaca nemestrina.

The early kinetics of antibody expression following transmucosal infection by SIV(Mne) were examined in several mucosal compartments in Macaca nemestrina. Five male-female pairs of macaques were inoculated intrarectally with SIV(Mne) E11S, a biological clone, and serially euthanized at 1, 2, 4, 8, and 12 weeks postinoculation. Plasma, tears, saliva, rectal secretions, and vaginal washes were collected serially and just prior to euthanasia. Both total and SIV-specific IgG and IgA levels were measured by immunoglobulin isotype-specific quantitative enzyme-linked immunosorbent assays (ELISAs), and were further examined by conventional and enhanced chemiluminescence (ECL) immunoblots. Virus coculture, polymerase chain reaction, and in situ hybridization assays revealed the systemic spread of virus as early as 1 week postinoculation in 8 of 10 animals. ECL immunoblots detected SIV-specific antibodies in mucosal samples collected 1 week postinoculation. The most dramatic increases in both total and SIV-specific IgA levels were detected in rectal secretion samples. In contrast, plasma and nonrectal mucosal samples from the same time points increased only slightly, suggesting that the most robust antibody response occurred at the portal of infection. Our results show that the SIV-infected macaque is an excellent model for studies designed to assess mucosal immune responses to primate lentivirus infections. Additional studies will assess the correlation between the antiviral protection afforded by candidate vaccines and mucosal antibody responses.

Animals↗
PubMed1998

Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study.

Polycystic ovary syndrome (PCOS), a disorder of hyperandrogenism and chronic anovulation affects 5%-10% of all women. Women with PCOS often have elevated cardiovascular risk factors. A total of 244 PCOS cases were identified through the Division of Reproductive Endocrinology at Magee-Womens Hospital and were age-matched to 244 neighborhood controls. The average age of cases and controls was 35.3 +/- 7.4 and 36.7 +/- 7.7. Women with PCOS compared to controls had substantially higher LDL-C and total cholesterol levels at each age group under 45 years after adjustment for body mass index, hormone use, and insulin levels. In the over 40-year age group, little difference was noted between cases and controls. Among cases and controls (<40), PCOS predicted LDL-C, total cholesterol and triglycerides, but did not have a significant effect on lipid levels in older cases and controls after controlling for the other variables. The primarily pre- to perimenopausal PCOS cases > or =40 years of age have similar LDL-C and total cholesterol levels as their age-matched controls, probably reflecting the LDL-C increase with age among controls.

Adult↗
PubMed1998

Differences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study.

A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3% for white women, 39.7% for black women, 41.9% for white men, and 43.7% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.

Black or African American↗
PubMed1998

Mechanisms of clearance of Treponema pallidum from the CSF in a nonhuman primate model.

OBJECTIVES: To establish a model of CNS invasion by Treponema pallidum and to use it to investigate the immune mechanisms responsible for clearance. METHODS: Four macaques were intrathecally inoculated with 0.6 to 2.1 x 10(8) T. pallidum and underwent clinical examinations and blood and CSF collections every 1 to 2 weeks for 12 to 13 weeks. The following were determined: serum Venereal Disease Research Laboratory (VDRL) and microhemagglutination-T. pallidum reactivities, CSF-VDRL, CSF white blood cell (WBC) count, and the presence of viable T. pallidum in CSF by the rabbit infectivity test (all animals), as well as the presence of T. pallidum in CSF by reverse transcriptase (RT)-PCR, WBC phenotype by fluorescence-activated cell sorter, WBC cytokine production by RT-PCR, and brain MRI at 10 weeks (two animals). RESULTS: All animals became systemically infected and developed CSF pleocytosis that resolved after 8 weeks. CSF T. pallidum was detected from 2 to 8 weeks. CSF T lymphocytes were predominantly CD4+. Interferon-gamma (IFN-gamma) mRNA was consistently detected in CSF WBCs, but interleukin (IL)-4 and IL-5 were not. All animals remained clinically well. MRIs were normal. CONCLUSIONS: In this model, T. pallidum is cleared from the CNS just as in most humans with early syphilis. Local production of IFN-gamma likely participates in this process. This model could be used to clarify the effect of retrovirus-induced immunodeficiency on clearance of T. pallidum from the CNS and on the local CNS immune response.

Animals↗
PubMed1998

Was there an epidemic of diabetes in nonwhite adolescents in Allegheny County, Pennsylvania?

OBJECTIVE: To determine the incidence of IDDM in children aged < 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period. RESEARCH DESIGN AND METHODS: All new patients diagnosed between January 1990 and December 1994 who were aged < 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source. RESULTS: A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15-19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000). CONCLUSIONS: For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15-19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.

Adolescent↗
PubMed1997

Focal segmental glomerulosclerosis in primates infected with a simian immunodeficiency virus.

Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) is the typical lesion of human HIV-associated glomerulopathy. Autopsy studies showed the presence of FSG in 3 of 15 macaques dying 15-120 weeks after experimental infection with a simian immunodeficiency virus (SIVMne). Ultrastructural studies generally revealed numerous endothelial TRIs (also present in normals), mesangial expansion, and evidence of mesangial cell injury. One additional animal had a small-vessel polyarteritis with a proliferative and focally crescentic glomerulonephritis; seven animals had mild, multifocal interstitial nephritis. All animals had documented viremia after infection; 14 of 15 developed antibodies to SIV postinoculation. Additional postmortem findings included severe enterocolitis, encephalitis, and opportunistic infections. In contrast, autopsy studies of macaques infected with a type D simian retrovirus (SAIDS-D/Washington, SRV-2) for similar periods of time (n = 40) showed no evidence of FSG. One SRV-infected animal had a mild proliferative glomerulonephritis. These studies indicate SIV-infected primates may provide a relevant model for study of human HIV-associated nephropathy. They also indicate the variable pathology that can be seen in primate infections of distinct retrovirus types, each of which produces a simian immunodeficiency state that resembles human AIDS.

AIDS-Associated Nephropathy↗
PubMed1996

Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial.

Few prospective data are available regarding the association of sex hormone-binding globulin (SHBG), testosterone, and the risk of developing diabetes. Stored fasting serum samples from participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) at 22 centers throughout the United States from December 1973 through February 1976 were used to perform a nested case- control study. For 176 initially nondiabetic men who had developed diabetes during 5 years of follow-up, two controls were selected, one matched only for randomization date, treatment group, and clinic ("loose controls") and the other matched additionally for fasting glucose and body mass index ("tight controls"). When cases were compared with lose controls, higher levels of fasting insulin and lower levels of total and free testosterone and SHBG were significantly associated with increased development of diabetes. However, when cases were compared with tightly matched controls, these associations weakened considerably. Low SHBG and testosterone may constitute part of the prediabetic state in men along with previously reported variables, such as higher glucose and insulin levels and obesity.

Adult↗
PubMed1996

Does visceral adipose tissue differ from subcutaneous adipose tissue in fatty acid content?

OBJECTIVE: To determine whether intra-abdominal adipose tissue differs from subcutaneous adipose tissue in fatty acid content. DESIGN: Cross-sectional study of patients undergoing exploratory laparotomy, with adipose tissue sampling from subcutaneous, omental, mesenteric and retroperitoneal sites. SUBJECTS: Nineteen subjects, 8 men and 11 women, with a mean age of 64 (range 39-80), mean weight 78.9 kg (range 51-157) and mean body mass index of 27.5 (range 19.2-51.4). Fourteen of the 19 were undergoing surgery for colorectal cancer. MEASUREMENTS: Fatty acid content was assessed by gas chromatography and was compared between sites and between patients using general linear modeling. Spearman correlation coefficients were used to assess the association between subcutaneous and visceral adipose tissue. RESULTS: For each of 17 fatty acids analyzed, there was a statistically significant difference in mean fatty acid values across individuals (p < 0.001). For seven of the fatty acids, there was a borderline or significant difference in mean fatty acid values across site, but there was no consistent pattern for one site differing from the others. Subcutaneous adipose tissue fatty acid content was highly correlated to visceral adipose tissue for saturated, unsaturated and trans fatty acids (p < 0.05 for 13 of 17 fatty acids). Variability across individuals was much greater than across site. The total explained variability (R2) for each fatty acid ranged between 49 and 93%, with the vast majority contributed by differences between individuals. CONCLUSION. Fatty acid content of subcutaneous abdominal adipose tissue is a good approximation of visceral adipose tissue. Because variability in fatty acid content is much larger between individuals than within a single individual across sites, subcutaneous abdominal adipose tissue fatty acid content can be used as a distinguishing characteristic among human populations.

Adipose Tissue↗
PubMed1995

High mortality from unidentified CVD in IDDM: time to start screening?

Mortality in insulin-dependent diabetes is markedly increased compared to the general population. Although strong associations have been found between renal disease and the risk of cardiovascular disease (CVD) the interaction between these two factors is not well understood. This study, which addresses risk factors for mortality in IDDM with a particular focus on the renal-CVD link, is based on the prospective Epidemiology of Diabetes Complications study. Thirty-seven (mean age 36 years, mean duration of IDDM 28 years at baseline) of the 658 IDDM individuals (mean age 28 years, mean duration of IDDM 20 years at baseline) have died in the first 4 years of follow up. A nested case-control study was performed, matching on sex and duration of diabetes. Twenty-two (59%) of the deaths were attributed to coronary heart disease, with an additional 16% attributed to diabetic coma. Only nine (41%) of the 22 individuals who died from cardiovascular disease had clinical evidence of coronary heart disease when seen for their last biennial exam. However, 54% of those who died of CVD without prior evidence did have evidence of lower extremity arterial disease. A strong link with renal disease was confirmed, with 81% of those with a coronary artery disease death having renal disease. Multivariate analyses suggest that smoking history, triglycerides and total platelet count are independent predictors of mortality, while LDL cholesterol best predicted CVD mortality. These results suggest a need for more intensive screening for cardiovascular disease, and correction of cardiovascular risk factors, in order to reduce the increased rate of mortality in this population. Efforts to prevent or delay the onset of renal disease may also be of benefit.

Adult↗
PubMed1995

Coronary heart disease risk factors in women with polycystic ovary syndrome.

The goal of the study was to compare cardiovascular heart disease risk factors in women with polycystic ovary syndrome (PCOS) and matched control subjects. Women with PCOS have risk factors, including anovulation, hyperandrogenism, and insulin resistance, that suggest a male coronary heart disease risk-factor profile. A total of 206 women with PCOS were recruited by using records from a large reproductive endocrinology practice. A clinical diagnosis of PCOS was made if there was a history of chronic anovulation in association with either clinical evidence of androgen excess (hirsutism) or if total testosterone level was > 2 nm/L or the luteinizing hormone/follicle-stimulating hormone ratio was greater than 2. The overall response rate for cases was 76%. A control population was obtained by using a combination of area voters' registration tapes and directories of households. A control subject was matched to each case subject by age +/- 5 years, race, and neighborhood. The response rate for recruitment of the first or second eligible control subject was 83.6%. The average age at initial interview was 35.9 +/- 7.4 years for case and 37.2 +/- 7.8 years for control subjects. Women with PCOS had significantly increased cardiovascular disease risk factors compared with control women. These included increases in body mass index, insulin, and triglyceride levels (P < .001), decreased total HDL and HDL2 levels (P < .01), and increased total cholesterol and fasting LDL levels, waist/hip ratio, and systolic blood pressure (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Genetic determination of coagulation factor VIIc levels among healthy middle-aged women.

A recent study (1) reported variation among men in clotting factor VIIc levels is associated with a genetic polymorphism detected by the restriction enzyme Msp I. The present study determined the Msp I genotype (Arg353, Gln353 alleles) for 189 women (mean age 53) who were subjects in the Healthy Women Study, a population study of CHD risk factor change at menopause. Women with the Arg/Arg genotype (n = 147) had an 16% higher (geometric) mean FVIIc level than those with the Arg/Gln (n = 41) genotype (1.21 vs 1.04 U/ml, p < 0.01), while the one subject with the Gln/Gln genotype had an FVIIc level of 1.00 U/ml. These results are consistent with those previously found in healthy men (1). In addition, women carrying the Gln allele did not exhibit the elevation in FVIIc with menopause and use of hormone therapy found among those with the Arg allele, suggesting that genotype may modify the observed rise in factor VIIc at menopause. Possibly because of the small sample size this interaction did not reach conventional levels of statistical significance. Results of multiple linear regression analyses controlling for age, hormone use, obesity, (ln) triglyceride levels, and family history of CHD found FVIIc levels to be significantly (p < 0.001) related to genotype. Thus, genotype appears to be a major determinant of FVIIc levels among women.

Adult↗
PubMed1994

Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study.

The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36% in women and 38.7% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease.

Aged↗
PubMed1994

T-cell proliferation to subinfectious SIV correlates with lack of infection after challenge of macaques.

OBJECTIVES: To analyze correlates of protection in macaques exposed to SIV. METHODS: Peripheral blood mononuclear cells (PBMC) from macaques inoculated intrarectally with various dilutions of SIV were examined for their in vitro proliferative response to SIV envelope peptides and generation of SIV-specific antibodies. Some macaques previously exposed intravenously to subinfectious doses of SIV were subsequently challenged 16 months later with an infectious intrarectal dose of SIV. RESULTS: The viral-specific immune responses of macaques exposed to infectious doses of SIV were characterized by generation of antibodies and weak or undetectable T-cell-mediated responses. In contrast, macaques inoculated with doses of SIV below the threshold required for seroconversion and recovery of virus exhibited T-cell proliferation in response to SIV envelope synthetic peptides. The macaques that had previously been exposed to SIV resisted the subsequent virus challenge, whereas the naive macaques (never exposed to SIV) all became infected. CONCLUSIONS: The inability to productively infect macaques previously exposed to subinfectious doses of SIV suggests that a T-cell-mediated response may confer long-term protection against infection, and that AIDS vaccines should be designed to optimize the cellular arm of the immune response.

Amino Acid Sequence↗
PubMed1994

Intrarectal inoculation of macaques by the simian immunodeficiency virus, SIVmne E11S: CD4+ depletion and AIDS.

Macaca nemestrina and Macaca fascicularis were inoculated with various doses of a single-cell clone of SIVmne-infected HuT 78 cells (E11S) by both the intravenous and intrarectal routes. Animals inoculated intravenously at each dose seroconverted and virus was isolated from peripheral blood mononuclear cells, but only the high-dose intrarectally exposed macaques became viremic and seroconverted. However, some seronegative, virus isolation negative intrarectally inoculated macaques showed evidence of infection and disease.

Animals↗
PubMed1993

Risk factors for death from different types of stroke. Multiple Risk Factor Intervention Trial Research Group.

UNLABELLED: The objective of this study was to investigate risk factors for death from different types of stroke among men screened for the Multiple Risk Factor Intervention Trial (MRFIT). A total of 353,340 men were screened by 20 centers for the MRFIT in 1973 to 1975; vital status has been ascertained over an average of 12 years of follow-up (range: 11 to 13 years). Death certificates were coded using the International Classification of Diseases (ICD), ninth revision. Deaths from stroke were classified as death from subarachnoid hemorrhage (ICD code 430), death from intracranial hemorrhage (ICD codes 431 and 432), death from nonhemorrhagic stroke (ICD codes 433 through 438), and death from any type of stroke (ICD codes 430 through 438). RESULTS: During an average of approximately 12 years of follow-up, 765 deaths from stroke were identified; 139 of these deaths were attributable to subarachnoid hemorrhage; 227, to intracranial hemorrhage; and 399 were classified as nonhemorrhagic stroke. Blood pressure and cigarette smoking were strongly related to each type of stroke. Systolic blood pressure was a stronger predictor than diastolic blood pressure. With the exception of subarachnoid hemorrhage, death rates from each type of stroke increased with age and were higher for black men. The positive association of age and race with subarachnoid hemorrhage was much weaker than for the other types of stroke and was not significant. Income was inversely associated with risk of death from nonhemorrhagic stroke and was not associated with either subarachnoid or intracranial hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗