George D. Montoya

A population-based study of human papillomavirus genotype prevalence in the United States: baseline measures prior to mass human papillomavirus vaccination.

Currently, two prophylactic human papillomavirus (HPV) vaccines targeting HPV 16 and 18 have been shown to be highly efficacious for preventing precursor lesions although the effectiveness of these vaccines in real‐world clinical settings must still be determined. Toward this end, an ongoing statewide surveillance program was established in New Mexico to assess all aspects of cervical cancer preventive care. Given that the reduction in cervical cancer incidence is expected to take several decades to manifest, a systematic population‐based measurement of HPV type‐specific prevalence employing an age‐ and cytology‐stratified sample of 47,617 women attending for cervical screening was conducted prior to widespread HPV vaccination. A well‐validated polymerase chain reaction (PCR) method for 37 HPV genotypes was used to test liquid‐based cytology specimens. The prevalence for any of the 37 HPV types was 27.3% overall with a maximum of 52% at age of 20 years followed by a rapid decline at older ages. The HPV 16 prevalences in women aged ≤20 years, 21–29 years or ≥30 years were 9.6, 6.5 and 1.8%, respectively. The combined prevalences of HPV 16 and 18 in these age groups were 12.0, 8.3 and 2.4%, respectively. HPV 16 and/or HPV 18 were detected in 54.5% of high‐grade squamous intraepithelial (cytologic) lesions (HSIL) and in 25.0% of those with low‐grade SIL (LSIL). These baseline data enable estimates of maximum HPV vaccine impact across time and provide critical reference measurements important to assessing clinical benefits and potential harms of HPV vaccination including increases in nonvaccine HPV types (i.e., type replacement).

Serum leptin levels, bone mineral density and osteoblast alkaline phosphatase activity in elderly men and women

Although primarily secreted by adipose cells, leptin, a polypeptide hormone that influences body weight, satiety and lipid metabolism, and its receptor are also expressed in human osteoblasts. Leptin plays a role in the central, hypothalamic modulation of bone formation, as well as locally within the skeleton by enhancing differentiation of bone marrow stroma into osteoblasts and inhibiting its differentiation into osteoclasts and adipocytes. The purpose of this investigation was to compare serum leptin values in 100 postmenopausal women (age 62-97) and 31 men (age 72-92) to bone mineral density (BMD) measurements made by dual X-ray absorptiometry and additionally to biochemical markers of bone resorption and formation, including crosslinked collagen N-telopeptides (NTx), aminoterminal extension procollagen propeptides (PINP) and bone-specific alkaline phosphatase (bAP). The circulating level of leptin directly correlated with body mass index (BMI) (r=0.61-0.78, P<0.001) and was modestly, but significantly and positively associated with bAP activity (r=0.24-0.33, P<0.01) in the sera of men and women after adjustment for BMD, age and BMI. The association of circulating leptin levels with bAP, a specific marker of osteoblast activity suggests that leptin levels influence osteoblast activity in vivo in elderly women and men.

Critical differences in the serial measurement of three biochemical markers of bone turnover in the sera of pre- and postmenopausal women.

OBJECTIVES The purpose of this investigation was to quantify the biologic, day-to-day variability and critical differences in serum levels of crosslinked collagen N-telopeptides (NTx), procollagen aminoterminal extension propeptides (PINP) and bone specific alkaline phosphatase (bAP) in healthy women. DESIGN AND METHODS Seven blood samples were collected from 12 pre- and 15 postmenopausal women over 4 to 6 months. NTx, PINP and bAP levels were determined utilizing enzyme- and radioimmunoassay techniques. RESULTS The within-subject coefficient of variation (C.V.) in serum bAP, NTx and PINP levels was 7.1, 10.6 and 12.4% respectively. These variances did not differ significantly among premenopausal women when compared with postmenopausal subjects. Combining terms for analytical and biologic variability revealed that a critical difference between 2 successive serial measurements is 24% for bAP, 34% for NTx and 38% for PINP. CONCLUSION Circulating levels of NTx, PINP and bAP are stable over time periods of several months, allowing for the determination of significant changes in skeletal metabolism of women.

Diagnostic efficacy of serum cross-linked N-telopeptide (NTx) and aminoterminal procollagen extension propeptide (PINP) measurements for identifying elderly women with decreased bone mineral density.

The purpose of this study was to determine the diagnostic sensitivity, specificity, predictive value and overall efficiency of serum cross-linked N-telopeptides of bone collagen (NTx) and aminoterminal procollagen extension propeptide (PINP) measurements for identifying women with decreased spine, femoral neck and total body bone mineral density (BMD). Serum NTx and PINP levels and dual X-ray absorptiometry were performed on 196 healthy elderly women, aged 60-90 years. Twelve women were classified as having decreased BMD on the basis of regional and total skeletal densitometric values that were 1.5 to 2.5 standard deviations (SD) below the respective, age-stratified means and were compared with184 women with BMD values greater than 1.5 SD below the mean. The results of receiver operating characteristic analysis revealed that a cutoff level of more than 15.0 nmol BCE/L for serum NTx, as measured by the Osteomark assay (Ostex International, Seattle WA USA) was associated with a 100% sensitivity and 70% specificity rate for identifying postmenopausal women with low BMD. The positive likelihood ratio was 3.3 and the negative predictive value was 1.0 using the 15.0 nmol decision level for NTx. The overall diagnostic efficiency of a single NTx measurement for identifying women with low BMD was 89%. A cutoff level of > 45.0 mug/L for PINP as measured by the Orion Diagnostica RIA assay (Espoo, Finland) had a diagnostic sensitivity of 83% and specificity of 64% for identifying women with decreased BMD. The positive likelihood ratio was 2.3, the negative predictive value 0.98 and the overall diagnostic efficiency 73% using the 45.0 mug/L decision level for PINP. These results warrant future studies using larger populations that are inclusive of more women with low bone mineral density.

Allelic diversity within the high frequency Mamu-A2*05/Mane-A2*05 (Mane-A*06)/Mafa-A2*05 family of macaque MHC-A loci

Macaque species serve as important animal models of human infection and immunity. To more fully scrutinize their potential in both the analysis of disease pathogenesis and vaccine development, it is necessary to characterize the major histocompatibility complex (MHC) class I loci of Macaca mulatta (Mamu), Macaca nemestrina (Mane), and Macaca fascicularis (Mafa) at the genomic level. The oligomorphic Mamu-A2*05/Mane-A2*05 (previously known as Mane-A*06) family of macaque MHC-A alleles has recently been shown to be present at high frequency in both Indian rhesus and pig-tailed macaque populations. Using a locus-specific amplification and direct DNA typing methodology, we have additionally found that the locus encoding this family is very prevalent (75%) among a sampling of 182 Chinese rhesus macaques and has a high prevalence (80%) within a larger, independent cohort of 309 pig-tailed macaques. Interestingly, among the Chinese rhesus macaques, only six alleles previously identified in Indian-origin animals were observed, while three recently identified in Chinese-origin animals and 25 new alleles were characterized. Among the pig-tailed macaques, we observed 1 previously known (Mane-A*06) and 19 new alleles. Examination of the orthologous locus in a preliminary sampling of 30 cynomolgus macaques showed an even higher presence (87%) of Mafa-A2*05 family alleles, with 5 previously identified and 15 new alleles characterized. The continued discovery of novel alleles and thus further diversity within the Mamu-A2*05/Mane-A2*05/Mafa-A2*05 family indicates that this MHC-A locus, although highly conserved across the three species of macaques, has remained a dynamic entity during evolution.