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PubMed1984

Relationship of ventilatory capacity to hyperbaric exposure in divers.

The results of divers' annual medical examinations were used to assess the effects of diving exposure independent of age, stature, and smoking on forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Cross-sectional analysis of records for 858 men showed a significant positive association between the maximal depth that subjects had experienced and FVC but not FEV1. There was a significant negative association for FEV1/FVC%, and this index was also positively correlated with years of diving exposure. Among a subsample of 81 men the forced expiratory flow rate at low lung volume was reduced relative to that of control subjects similarly assessed; the extent of the reduction from the reference value was significantly correlated with the diving exposure. Longitudinal analysis of results for 255 men over a minimum of 5 yr showed that the change in FVC per annum (positive or negative) was correlated with the change in maximal depth; there were no similar associations for FEV1 or FEV1/FVC%. Thus diving exposure affects the vital capacity and the forced expiratory flow rate at small lung volumes. The latter is evidence for narrowing of airways that might be secondary to diving-induced loss of lung elastic tissue; this hypothesis merits further investigation.

Adult↗

PubMed2002

Serum thyroxine level and cognitive decline in euthyroid older women.

BACKGROUND: Clinical and subclinical hypothyroidism is associated with cognitive impairment. OBJECTIVE: This study investigated the association between thyroxine (T(4)) and thyroid-stimulating hormone (TSH) level and change over time in cognitive performance in a sample of older women with normal thyroid gland function. METHODS: T(4) and TSH were measured at baseline in 628 women (> or = 65 years) enrolled in the Women's Health and Aging Study, a community-based study of physically impaired women. Cognitive function was assessed at baseline and after 1, 2, and 3 years, using the Mini-Mental State Examination (MMSE). Incident cognitive decline was defined as a decrease of more than one point/year in MMSE score between baseline and the end of the follow-up. The analysis included 464 subjects with normal thyroid gland function with a baseline and at least one follow-up MMSE. RESULTS: At baseline there was no association between T(4) and TSH level and cognitive function. In longitudinal analysis, adjusting for age, race, level of education, and other covariates, compared with women in the highest T(4) tertile (8.1 to 12.5 microg/dL), those in the lowest tertile (4.5 to 6.5 microg/dL) had a greater decline in MMSE score (-0.25 point/year vs -0.12 point/year; p = 0.04). A total of 95 women (20.5%) had cognitive decline during the study period (mean MMSE decline, 5.5 points). Compared with women in the highest T(4) tertile, those in the lowest tertile had a twofold risk of cognitive decline (adjusted relative risk, 1.97; 95% CI, 1.10 to 3.50). The results were not modified by baseline cognitive and physical function. There was no association between baseline TSH level and change in cognitive function. CONCLUSIONS: In older women, low T(4) levels, within the normal range, were associated with a greater risk of cognitive decline over a 3-year period. Thyroid hormone levels may contribute to cognitive impairment in physically impaired women.

Aged↗

PubMed2003

Analysis of linear growth in survivors of childhood acute lymphoblastic leukemia.

Therapy for childhood acute lymphoblastic leukemia (ALL) is entering a new era in terms of quality-of-life. In the current study, 21 patients with childhood-onset ALL were assessed for linear growth, bone mineral density (BMD), and endocrinological status, focusing especially on longitudinal analysis of the growth of each patient. Linear growth was uniformly attenuated during therapy in all patients. In contrast, after the cessation of therapy, the growth of each patient varied widely from attenuated to dramatic catch-up growth. In pubertal survivors who had received chemotherapy and cranial irradiation during prepuberty, the degree of growth after the cessation of therapy was negatively correlated with changes in height Z scores during therapy ( r = -0.76, P= 0.004). One of the factors involved in catch-up growth, urinary N-telopeptide/creatinine (U-NTx/Cr), was significantly higher in patients whose Z scores decreased after cessation of therapy ( P = 0.01), despite normal pubertal development and normal endocrinological assessments. The present study revealed individual differences in linear growth after the cessation of therapy and suggests the importance of catch-up growth during puberty.

Adolescent↗

PubMed2002

Antiepileptic drug-induced bone loss in young male patients who have seizures.

BACKGROUND: Long-term antiepileptic drug (AED) therapy is a known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures. OBJECTIVE: To determine whether men who have seizures, but who are otherwise healthy, suffer substantial bone loss in the hip while taking AEDs. PATIENTS AND METHODS: We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years old (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time. RESULTS: Multivariate linear regression analysis revealed that age (P<.001) and time receiving AEDs (P<.003) were the 2 important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake were associated with low BMD after correcting for age and time on AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25-44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, -3.1 to -0.9; P<.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group although most patients were taking phenytoin sodium or carbamazepine during the longitudinal assessment. CONCLUSIONS: Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs.

Absorptiometry, Photon↗

PubMed1992

Profiles, correlates, and trajectories of intelligence in Prader-Willi syndrome.

Three aspects of intellectual functioning in persons with Prader-Willi syndrome were examined in two, related studies. In study 1, 21 subjects were evaluated with a psychometric instrument that assesses neuropsychological styles of cognitive processing, the Kaufman Assessment Battery for Children. Prader-Willi subjects showed deficits in sequential processing, and strengths in academic achievement tasks such as reading and vocabulary. In contrast to previous reports on the syndrome, no relationship was found between weight and degree of intellectual impairment. Study 2 included a cross-sectional examination of the trajectory of IQ in 21 subjects aged 13 to 46 years, as well as a longitudinal analysis of 31 subjects aged 5 to 30 years who were tested twice with the same IQ test. No evidence of the previously described decline in IQ over time was noted in either the cross-sectional or longitudinal analyses. The implications of these findings for interventions are discussed.

Achievement↗

PubMed1994

Naturally occurring genotypes of the human immunodeficiency virus type 1 long terminal repeat display a wide range of basal and Tat-induced transcriptional activities.

The primary body of information on the structure of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)/gag leader genotypes has been determined from the analysis of cocultivated isolates. Functional studies of this regulatory portion of the provirus have been derived from the study of in vitro-generated mutations of laboratory-adapted molecular clones of HIV-1. We have performed a longitudinal analysis of molecular clones from the LTR/gag leader region amplified directly from the peripheral blood of four patients over three years. We have found a remarkable number of point mutations and length polymorphisms in cis- and trans-acting regulatory elements within this cohort. Most of the length polymorphisms were associated with duplications of Sp1 and TCF-1 alpha sequences. These mutations were associated with a wide range of transcriptional activities for these genotypes in a reporter gene assay. Mutations in conserved Sp1 sequences correlated with a diminished capacity of such genotypes to bind purified Sp1 protein. Although no generalized trend in transcriptional activity was seen, a single patient accumulated mutations in NF-kappa B, Sp1, and TAR elements over this period. The analysis of naturally occurring mutations of LTR genotypes provides a means to study the molecular genetic consequences of virus-host interactions and to assess the functional impact of HIV therapeutics.

Base Sequence↗

PubMed2004

Low-normal gestational age as a predictor of asthma at 6 years of age.

BACKGROUND: Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear. METHODS: Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses. RESULTS: Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 0.40-2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7; 95% CI: 2.1-10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15; 95% CI: 2.98-22.3; girls: OR: 1.90; 95% CI: 0.38-13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences. CONCLUSIONS: Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific.

Analysis of Variance↗

PubMed2006

HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time.

OBJECTIVE: Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains. PATIENTS AND METHODS: Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients. Phylogenetic analysis of HIV DNA protease gene clones was used to explore the diversity of quasi-species at baseline. RESULTS: Baseline resistance profile was identical in paired HIV RNA and PBMC HIV DNA for all 44 patients. All resistance-associated mutations persisted in plasma and PBMC over 2 years in the five untreated patients. Of the five patients started on empirical HAART, two achieved undetectable HIV RNA at month 6, with long-term persistence of archived drug-resistance mutations in PBMC HIV DNA. Virological failure was observed in the other three patients, resulting in the accumulation of additional drug-resistance mutations in HIV RNA and HIV DNA for two of them. Phylogenetic analysis of HIV DNA clones showed highly homogenous and exclusively resistant quasi-species in the cellular reservoir at baseline. CONCLUSION: HIV resistant strains acquired at the time of PHI massively fuel the cellular reservoir, and their prolonged persistence is supported by the early expansion of a dominant homogenous and resistant viral population. Results in treated patients showed that classical empirical triple-combination may be suboptimal.

Adult↗

PubMed2006

A cost analysis of the Iowa Medicaid primary care case management program.

OBJECTIVE: To determine the cost savings attributable to the implementation and expansion of a primary care case management (PCCM) program on Medicaid costs per member in Iowa from 1989 to 1997. DATA SOURCES: Medicaid administrative data from Iowa aggregated at the county level. STUDY DESIGN: Longitudinal analysis of costs per member per month, analyzed by category of medical expense using weighted least squares. We compared the actual costs with the expected costs (in the absence of the PCCM program) to estimate cost savings attributable to the PCCM program. PRINCIPAL FINDINGS: We estimated that the PCCM program was associated with a savings of US dollars 66 million to the state of Iowa over the study period. Medicaid expenses were 3.8 percent less than what they would have been in the absence of the PCCM program. Effects of the PCCM program appeared to grow stronger over time. Use of the PCCM program was associated with increases in outpatient care and pharmaceutical expenses, but a decrease in hospital and physician expenses. CONCLUSIONS: Use of a Medicaid PCCM program was associated with substantial aggregate cost savings over an 8-year period, and this effect became stronger over time. Cost reductions appear to have been mediated by substituting outpatient care for inpatient care.

Adolescent↗

PubMed1999

Neuropsychometric tests in cross sectional and longitudinal studies - a regression analysis of ADAS - cog, SKT and MMSE.

INTRODUCTION: In clinical and drug studies, different neuropsychometric tests are used. So far, no empirical data have been published to compare studies using different tests. The purpose of this study was to calculate a regression formula allowing a comparison of cross-sectional and longitudinal data from three neuropsychometric tests that are frequently used in drug studies (Alzheimer's Disease Assessment Scale, ADAS-cog; Syndrom Kurz Test, SKT; Mini Mental State Examination, MMSE). METHOD: 177 patients with dementia according to ICD10 criteria were studied for the cross sectional and 61 for the longitudinal analysis. Correlations and linear regressions were calculated between tests. Significance was proven with ANOVA and t-tests using the SPSS statistical package. RESULTS: Significant Spearman correlations and slopes in the regression occurred in the cross sectional analysis (ADAS-cog-SKT r(s) = 0.77, slope = 0.45, SKT-ADAS-cog slope = 1.3, r2 = 0.59; ADAS-cog-MMSE r2 = 0.76, slope = -0.42, MMSE-ADAS-cog slope = -1.5, r2 = 0.64; MMSE-SKT r(s) = -0.79, slope = -0.87, SKT-MMSE slope = -0.71, r2 = 0.62; p<0.001 after Bonferroni correction; N = 177) and in the longitudinal analysis (SKT-ADAS-cog, r(s) = 0.48, slope = 0.69, ADAS-cog-SKT slope = 0.69, p<0.001, r2 = 0.32, MMSE-SKT, r(s) = 0.44, slope = -0.41, SKT-MMSE, slope = -0.55, p<0.001, r2 = 0.21). CONCLUSIONS: The results allow calculation of ADAS-scores when SKT scores are given, and vice versa. In longitudinal studies or in the course of the disease, scores assessed with the ADAS-cog and the SKT may now be statistically compared. In all comparisons, bottom and ceiling effects of the tests have to be taken into account.

Aged↗

PubMedDate not supplied

Impairment of neocortical metabolism predicts progression in Alzheimer's disease.

Progression rates of Alzheimer's disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment. Copyrightz1999S.KargerAG, Basel

Aged↗

PubMed1997

Modulation and detection of IDDM by membrane associated antigens from the islet beta cell line NIT-1.

We have utilized the NOD islet beta-cell line NIT-1 to monitor beta-cell specific autoantibodies and to investigate the modulation of IDDM in NOD mice by NIT-1 membrane associated antigens. The sera from diabetic but not from pre-diabetic or protected NOD mice strongly stained NIT-1 cells in FACS analysis. The cell surface antigens on NIT-1 cells were trypsin-sensitive. NIT-1 cells could not be stained by anti-mouse GAD67 antibody; however, we could demonstrate the presence of GAD65 and GAD67 mRNA by RT-PCR. Longitudinal analysis of anti-NIT-1 antibodies showed that these antibodies were present in the neonates but disappeared after weaning. Sonicated NIT-1 cell membrane preparations protected NOD mice from diabetes when injected intravenously in 5 week old mice. The protection was associated with reduced cytotoxic activity and elevated Th2-like responses as indicated by IgG1 antibodies against the NIT-1 cells. Subcutaneous injection of sonicated NIT-1 membranes or the injection of control red blood cell membranes failed to induce protection. We conclude that NIT-1 cell membranes do not express GAD but contain other antigens that are important in the development and prevention of IDDM. These antigens could be useful for the diagnosis of diabetes by monitoring autoantibody levels and for the modulation of IDDM by immunotherapy.

Animals↗

PubMed1998

Controlling for the endogeneity of peer substance use on adolescent alcohol and tobacco use.

This study examines whether the effects of peer substance use on adolescent alcohol and tobacco use are due to endogeneity of adolescents selecting their peer group. We analyzed data collected for a longitudinal analysis of a drug-use prevention programme for upper elementary school students. We used a two-step probit regression to control for the potentially endogenous explanatory variable peer substance use. Rigorous tests of endogeneity and the validity of the instrumental variables showed that controlling for the endogeneity of peer substance use to reduce bias is not worth the reduction in mean squared error in these data. Peer substance use has a positive and significant effect on adolescent substance use for both drinking and smoking. These results imply that peer influence is empirically more important than peer selection (endogeneity) in our sample of adolescents in grades 6-9. Living in a single-parent family was by far the strongest predictor of adolescent drinking and smoking.

Adolescent↗

PubMed1991

Serum fructosamine/haemoglobin A1 ratio predicts the future changes in haemoglobin A1 in type 2 (non-insulin dependent) diabetic patients.

The aim of the study was to define clinical interpretation of the parallel measurements of serum fructosamine and HbA1 in diabetic patients. We studied 14 type 2 diabetic patients over a 16-wk period. The cross-sectional analysis showed no correlation between serum fructosamine and HbA1 concentrations during the period of changing glycaemic control. The correlations, however, became significant (P less than 0.05) at 12 (r = 0.60) and 16 (r = 0.87) weeks, i.e. after glycaemia had stabilised. Longitudinal analysis of individual patients' data over the 16-wk period showed a significant correlation between serum fructosamine and HbA1 (r = 0.55 to r = 0.94) which was present in 8 out of 14 patients. The changes in fructosamine concentration preceded those observed in HbA1. The ratio of fructosamine/HbA1 predicted the changes in HbA1 over the following month (r = 0.54, P less than 0.001). Thus, we demonstrated that the parallel measurement of fructosamine and HbA1 provides information on future trends in HbA1 concentration in diabetic patients.

Adult↗

PubMed2005

Role of the growth hormone/insulin-like growth factor-1 paracrine axis in rheumatic diseases.

OBJECTIVES: Hypothalamic-pituitary axis abnormalities have been associated with systemic disturbances in several rheumatic diseases. Longitudinal analysis of erythrocyte, serum, urinary and synovial fluid growth hormone (GH), insulin-like growth factor-1 (IGF-1), and somatostatin levels could provide important surrogate measures of disease activity in rheumatic diseases. METHODS: The authors reviewed the population and longitudinal studies literature on GH, IGF-1, and somatostatin levels in rheumatic disorders using the PubMed and Medlines databases from the National Library of Medicine. In addition to the literature search, primary data were analyzed for basal somatostatin levels in patients with hand, knee, and spine osteoarthritis (OA) as well as primary and secondary hip OA. RESULTS: A review of the literature supports the view that hypothalamic-pituitary axis dysfunction accompanies clinical symptoms in many rheumatic diseases. In studies from our laboratory, serum GH levels were elevated in patients with OA, rheumatoid arthritis (RA), fibromyalgia, and diffuse idiopathic skeletal hyperostosis but not in patients with gout, pseudogout, or systemic lupus erythematosus. In OA and RA, synovial fluid GH levels exceeded serum GH levels. However, the literature remains controversial regarding the significance of changes in IGF-1 levels in rheumatic disorders. Many studies support an inverse relationship between age and IGF-1. Elevated serum GH levels in various rheumatic diseases were not coupled to changes in serum IGF-1 in diffuse idiopathic skeletal hyperostosis, RA, and fibromyalgia. In particular, serum IGF-1 levels in OA were shown to be lower or no different compared with age-matched normal subjects. Further, in OA, impaired articular chondrocyte response to IGF-1 was attributed, in part, to low synovial fluid IGF-1 that further compromised IGF-1 chondrocyte responses as a result of increased levels of synovial fluid IGF-1 binding proteins. Of note, serum somatostatin levels and "specific" somatostatin receptor levels were often lower in RA and systemic lupus erythematosus, but basal serum somatostatin levels were generally not altered in OA. CONCLUSIONS: The results of these analyses support the view that some rheumatic diseases such as OA and diffuse idiopathic skeletal hyperostosis, heretofore considered to be purely focal and degenerative, could be reclassified as systemic metabolic disturbances. We propose that serum GH, IGF-1, and somatostatin levels be monitored on a longitudinal basis during the course of medical therapy of rheumatic diseases to determine the extent to which changes in clinical symptoms (exemplified by reduced pain and inflammation and improved range of joint motion) are accompanied by changes in the basal concentration of these hypothalamic/pituitary-related hormones.

Adult↗

PubMed1984

Lung function in Canadian Inuit: a follow-up study.

To assess the impact of acculturation on lung function, the forced vital capacity (FVC) and the 1-second forced expiratory volume (FEV1) of 341 Inuit at Igloolik, NWT were measured. The same observers had used the same equipment to test 196 subjects in 1970-71. Cross-sectional analysis suggested that, relative to the previous decade, younger subjects had larger lung volumes (with gains of about 10% in FVC and 5% in FEV1), while the elderly had smaller volumes (with losses of about 22% in FVC and 25% in FEV1). Longitudinal analysis confirmed an accelerating loss of lung function in the older subjects: from age 25 to 35 years men and women had a loss in FVC of 13 and 11 mL/yr respectively, whereas from age 45 to 55 years the corresponding figures were 70 and 38 mL/yr. Cigarette smoking had increased substantially among the Inuit over the decade: the proportion of males and females smoking rose from 64% to 81% and from 85% to 93% respectively. Daily cigarette consumption per smoker increased from 11.8 to 20.2 and from 7.4 to 12.0 among men and women respectively. Nevertheless, the main explanation for the shape of the ageing curve is the survival of a small cohort of elderly Inuit with advanced tuberculosis. With control of this disease future cohorts of the elderly will have better lung function.

Adolescent↗

PubMed1985

Cytotoxic reactivity of human natural killer (NK) cells during normal pregnancy: a longitudinal study.

A longitudinal analysis of natural killer (NK) cell-mediated cytotoxicity of maternal peripheral blood lymphocytes was carried out at various stages (16-36 weeks) of normal human pregnancy, within 1 week following delivery and up to 40 weeks post-partum. NK cell-mediated lysis of K562 target cells (TC) in short term 51Cr-release assays was significantly depressed throughout pregnancy, returning to control levels 9-40 weeks post-partum. Natural cytotoxicity of unseparated maternal peripheral blood was also substantially depressed at all stages of pregnancy and, in addition, remained impaired in the late post-partum period. Longitudinal enumeration of Leu 3a+ and Leu 2a+ lymphocytes indicated an absence of helper/suppressor T-cell imbalance during pregnancy, and analysis of Leu 7+ cells showed no difference in population sizes between control and pregnancy groups. Comparison of blood and lymphocyte cytotoxicity in control and pregnancy samples suggested a complex regulation of NK reactivity during pregnancy. The potential role in vivo of both plasma-associated and cellular regulatory elements is discussed.

Adolescent↗

PubMed1995

Characterization of a novel human antibody xenoreactive with fibronectin.

Recent reports have used bovine fibronectin (Fn) as source of antigen to study human anti-Fn autoantibodies. We have characterized a novel human antibody (Ab) reactive with bovine and marsupial Fn, but not with human Fn. Indirect immunofluorescence, wet cleaving and protein adherence assays, immunoblotting, blot-affinity purification, a cell adhesion inhibition assay, and competitive experiments with synthetic peptides were used to characterize the anti-Fn Ab in serum from a patient with an undifferentiated connective tissue disease. A characteristic Fn-like network was observed by indirect immunofluorescence on bovine MDBK and marsupial PtK2 cells, but not on various human cell lines. Double immunofluorescence revealed colocalization of the Ab with a mouse monoclonal anti-Fn Ab. A reactive polypeptide of 240 kDa corresponding to the M(r) of Fn was identified by immunoblotting using MDBK and PtK2 total cell lysates. The Ab reacted with the 240-kDa band of purified bovine Fn with an endpoint titer of 1:64,000, while no reactivity was observed with human cellular or plasma Fn. Blot-affinity purification of the Ab from the 240-kDa PtK2 region confirmed that the Fn-like fluorescent pattern observed was due to reactivity with the 240-kDa band and not with other regions of the blot. The Ab affinity-purified from the 240-kDa region also reacted with purified bovine Fn by immunoblotting. Functional analysis disclosed specific inhibition of PtK2 and MDBK cell adhesion by the affinity-purified anti-Fn Ab. Competitive experiments with synthetic peptides demonstrated that the epitope is located in the decapeptide RGDSPASSKP containing the cell-binding domain of Fn. Longitudinal analysis of the Ab revealed its persistence over 6 years. Bovine and marsupial Fn can be the focus of a highly specific and persistent human immune response. Reactivity of a human Ab with bovine Fn does not imply cross-reactivity with human Fn. In light of recent reports using bovine Fn to characterize human anti-Fn "autoantibodies," future studies on human anti-Fn should specifically employ purified human Fn as antigen.

Adult↗