Exposure of prepubertal beef bulls to cycling females does not enhance sexual development.

The objective of this study was to determine whether continuous, long-term, fenceline exposure of prepubertal beef bulls to cycling beef females reduced age at puberty and influenced the percentage of bulls that passed an initial breeding soundness examination (BSE). Bulls (Angus, n = 37; Simmental, n = 22; Hereford, n = 10; Simmental × Angus, n = 8) at an average age of 202 ± 21.5 days were given either continuous fenceline and visual exposure to cycling females (exposed, n = 41) or no exposure (control, n = 36). Estrus was induced in cycling beef females so at least three females were in standing estrus each week during the 182 days of exposure to bulls. Scrotal circumference (SC), body weight, and blood samples were collected every 28 days. When bulls had SC of 26 cm or more, semen samples were obtained monthly via electroejaculation until puberty was achieved (≥50 × 10(6) sperm/mL with at least 10% progressive motility). Behavioral observations were conducted twice monthly: once when females were in estrus and once during diestrus. Homosexual mounting, flehmen responses, and number of times near penned females were recorded for each observation period. Breeding soundness examinations were conducted when the average age of bulls was 364 ± 21.5 days. Normal sperm morphology of at least 70% and sperm motility of at least 30% were required to pass the BSE. Age, body weight, and SC at puberty did not differ between exposed and control bulls (320 ± 28 and 311 ± 29 days; 466.2 ± 12.2 and 437.7 ± 13.5 kg; and 34.4 ± 2.5 and 34.9 ± 2.5 cm, respectively). Percentage of bulls passing their initial BSE did not differ between treatments (exposed, 87.8%; control, 75.0%). Treatment, month, and female estrous stage interacted (P = 0.05) to affect the number of mount attempts and flehmen responses. Exposed bulls entered the cow area more times (P < 0.001) during estrus than diestrus in Months 1, 2, and 3. We concluded that bulls given continuous, long-term, fenceline exposure to cycling beef females do not have enhanced sexual development.

Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells.

Breast cancer is the most common solid tumor and the second most common cause of death in women. Despite a large body of literature and progress in breast cancer research, many molecular aspects of this complex disease are still poorly understood, hindering the design of specific and effective therapeutic strategies. To identify the molecules important in breast cancer progression and metastasis, we tested the in vivo effects of inhibiting the functions of various kinases and genes involved in the regulation/modulation of the cytoskeleton by downregulating them in mouse PyMT mammary tumor cells and human breast cancer cell lines. These kinases and cytoskeletal regulators were selected based on their prognostic values for breast cancer patient survival. PyMT tumor cells, in which a selected gene was stably knocked down were injected into the tail veins of mice, and the formation of tumors in the lungs was monitored. One of the several genes found to be important for tumor growth in the lungs was NIMA-related kinases 2 (Nek2), a cell cycle-related protein kinase. Furthermore, Nek2 was also important for tumor growth in the mammary fat pad. In various human breast cancer cell lines, Nek2 knockdown induced aneuploidy and cell cycle arrest that led to cell death. Significantly, the breast cancer cell line most sensitive to Nek2 depletion was of the triple negative breast cancer subtype. Our data indicate that Nek2 has a pivotal role in breast cancer growth at primary and secondary sites, and thus may be an attractive and novel therapeutic target for this disease.

Observation of nonmagnetic resonant scattering effects by tunneling in dilute Al-mn alloy superconductors.

We have observed the BCS-like density of states predicted for energy-gap suppression by nonmagnetic Anderson impurities in superconductors. We show that Mn impurities in Al exhibit no magnetic character and act exclusively as strong resonant scattering sites without producing time-reverse symmetry breaking of Cooper pairs (pair breaking).

A novel activating function of c-Src and Stat3 on HGF transcription in mammary carcinoma cells.

In the normal breast, hepatocyte growth factor (HGF) is primarily expressed by stromal cells, and stimulates in a paracrine manner epithelial cells expressing the HGF receptor (Met). In invasive human breast carcinomas, HGF and Met are frequently overexpressed, possibly establishing an autocrine HGF/Met loop that promotes tumour cell invasion. However, the mechanisms leading to autocrine HGF expression in carcinoma cells are not known. We previously demonstrated a cooperative effect between c-Src and Stat3 in the activation of HGF transcription in mammary carcinoma cells. The present report defines a novel Stat3 consensus site at nt -95 in the HGF promoter that is highly conserved in human and mouse, and is required for c-Src and Stat3 to activate HGF transcription in breast epithelial cells. DNA-protein binding studies demonstrated high affinity binding of a Stat3-containing complex to the nt -95 site. Endogenous Stat3 binding to this region of the HGF promoter in carcinoma cells expressing HGF was demonstrated using a chromatin immunoprecipitation assay. In addition, coexpression of Stat3 and activated c-Src caused increased expression of endogenous HGF mRNA and protein and marked cell scattering in breast epithelial cells. Our results delineate a novel c-Src/Stat3-dependent mechanism that regulates HGF promoter activity, and is linked to transformation of mammary epithelial cells.

Cross-hybridization of closely related genes on high-density macroarrays.

DNA macroarrays are used in many areas of molecular biology research for applications ranging from gene discovery to gene expression profiling. As an increasing number of specialized macroarrays containing genes related by function or pathway are becoming available, a question that needs to be addressed is the level of hybridization signal specificity between highly similar genes that can be achieved. We have examined the ability of our LifeGrid macroarrays to distinguish hybridization signals between closely related genes. We determined the level of cross-hybridization among genes ranging from 52% to 94% sequence identity. Fragments of genes fromfive protein families were arrayed onto nylonfilters. Thefilters were subsequently hybridized with a 33P-labeled probe prepared from a pool of synthetic mRNA transcripts containing a representative of each protein family. We found that fragments containing sequences with up to 94% sequence identity displayed relatively little cross-hybridization. We conclude that this macroarray system is very specific and that hybridization signals from closely related genes can be reliably measured.

Use of Medicaid 1915(c) home- and community-based care waivers to reconfigure state long-term care systems.

Since Congressional authorization in 1981, Medicaid 1915(c) home- and community-based care waivers have influenced states' efforts to transform their long-term care systems. In 1997, every state participated in the 1915(c) waiver program, while waiver expenditures, at $8.1 billion, represented 59.6 percent of all Medicaid community-based care expenditures. To explore state-level factors that appear related to these expenditures, the authors turn to a body of work on Medicaid resource allocation. They compare the influence of five factors--sociodemographic, supply, economic, programmatic, and political environment--on states' allocations to long-term care expenditures and 1915(c) waiver expenditures. The state economic environment was an important influence on total, as well as waiver expenditures. State regulation of long-term care supply demonstrated the most substantive relationship, increasing the share of dollars supporting 1915(c) waivers from 11.6 to 20.0 over the study period, all else equal.

In situ duct carcinoma of the breast: clinical and histopathologic factors and association with recurrent carcinoma.

There has been a recent increase in the diagnosis of in situ duct carcinoma of the breast (DCIS) as a result of mammographic screening. DCIS is heterogeneous in appearance and likely in prognosis. There is no generally accepted model to predict progression to invasive carcinoma. We investigated the prognostic effect of clinical presentation and pathologic factors for women diagnosed with primary DCIS. A cohort of 124 patients was accrued between 1979 and 1994 and was followed to 1997; 78 had DCIS detected mammographically, and 88 underwent lumpectomy alone. In this article, we provide details about characteristics affecting the choice of primary therapeutic modality, and we examine the effects of factors on progression for the two patient subgroups. Presentation with bloody nipple discharge was associated with a significant increase in DCIS recurrence (p=0.07). The pattern of duct distribution was important: DCIS in which the involved ducts were more widely separated had a significantly greater recurrence of DCIS than when the involved ducts were more concentrated (p=0.08 for mammographically detected DCIS, p=0.07 for patients who underwent lumpectomy alone). For mammographically detected DCIS, younger patients had more DCIS recurrence (p=0.07). We found considerable heterogeneity in nuclear grade; 50% of patients exhibited more than one grade. Nuclear grade, necrosis, and architecture were not significantly associated with either recurrence of DCIS or development of invasive carcinoma. Longer follow-up will allow further evaluation of the prognostic relevance of the factors assessed.

Regeneration of bone graft donor sites.

When crestal volume is greatly insufficient for the placement of dental implants, bone grafting is usually the most reliable ridge augmentation procedure. The grafts are most often taken in parietal or mandibular symphysis regions. Though not too noticeable, it seems contra-indicated and even potentially dangerous to leave zones like the cranium to repair spontaneously. Guided bone regeneration techniques have shown their ability to regenerate new bone under difficult conditions in jaws. Their use in bone graft donor sites is simple and the results are consistent. This report shows that 2 types of resorbable membranes are equally as efficacious in terms of new-bone formation.

Trends and issues in the Medicaid 1915(c) waiver program.

Over the past 15 years, Medicaid 1915(c) home and community-based waivers have made a substantial contribution to States' efforts to transform their long-term care (LTC) systems from largely institutional to community-based systems. By 1997, every State had implemented a waiver program for at least some subgroups of individuals with disabilities, and expenditures increased from $3.8 million in 1982 to more than $8.1 billion in 1997. Emerging, as well as long-standing, policy issues related to the waiver program include concerns with access, variation in availability by disability group, State decisions related to the provision of community-based LTC, and evidence on effectiveness.

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast.

BACKGROUND: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation. METHODS: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994. Primary therapy was a mastectomy for 18 patients, and a lumpectomy for 106 patients. Only 18 of the latter group of patients received adjuvant radiotherapy. For the 88 lumpectomy-alone patients (median follow-up, 5.2 years), we evaluated the effects of clinical (age and initial presentation) and pathologic (nuclear grade, architecture, parenchymal involvement, calcifications, and measured margins) factors on recurrence of DCIS or the development of invasive breast cancer. RESULTS: Patients who underwent lumpectomy with or without adjuvant radiotherapy (median follow-up, 5.0 years) were significantly more likely to have recurrence of DCIS (P=.05) than those who underwent mastectomy (median follow-up, 6.7 years): 18% (19/106) versus 0% (0/18), respectively; lumpectomy-alone patients experienced a 19% (17/88) rate of DCIS recurrence. All recurrent DCIS was ipsilateral. For lumpectomy-alone patients, the factors associated with ipsilateral recurrence of DCIS were extent of involvement of the parenchyma (P=.01, for univariate; P=.07, for multivariate) and initial presentation (P=.05, for univariate; P=.07, for multivariate). Eleven lumpectomy-alone patients developed invasive breast cancer (6 ipsilateral, 5 contralateral); none of the 18 lumpectomy patients who received adjuvant radiation developed invasive disease. None of the factors investigated, including primary surgery and adjuvant radiotherapy, were associated with a significant effect on the development of invasive disease. CONCLUSIONS: Longer follow-up is required to determine if the benefits of either mastectomy or radiotherapy following lumpectomy persist. There is a suggestion that patients under 40 years of age or women who present with nipple discharge might be considered for either adjuvant radiotherapy following lumpectomy or a simple mastectomy.

Joining forces to improve point-of-care testing.

Point-of-care (POC) testing takes a "laboratory" test directly to the patient's bedside. Although bedside testing is not new, the compliance standards are relatively new. Regulations ensure that all personnel are trained to properly perform the test. The central laboratory and nursing of this hospital merge the best skills of both units to create a successful POC testing program.

Transforming the long-term care system: policy and managerial challenges.

As the need for long-term care of people with disabilities increases, the model of care faces crucial changes, including a shift from institutional to independent living, significant changeover in organizational auspices, and policies created by the Americans with Disabilities Act. Such systemic changes pose fiscal, technological, and social challenges to policymakers and managers of care delivery.

Feasibility of obtaining breast epithelial cells from healthy women for studies of cellular proliferation.

Increased dietary fat intake and rate of breast epithelial cell proliferation have each been associated with the development of breast cancer. The goal of this study was to measure the effect of a low fat, high carbohydrate diet on the rate of breast epithelial cell proliferation in women at high risk for breast cancer. Women were recruited from the intervention and control groups of a randomized low fat dietary intervention trial, breast epithelial cells were obtained by fine needle aspiration, and cell proliferation was assessed in these samples using immunofluorescent detection of Ki-67 and PCNA. The effects of needle size and study group on cell yield and cytologic features of the cells were also examined. Fifty three women (20 in the intervention group and 33 in the control group) underwent the biopsy procedure. Slides from 38 subjects were stained for Ki-67 and from 14 subjects for PCNA. No cell proliferation (fluorescence) was detected for either Ki-67 or PCNA in any of the slides. Epithelial cell yield and number of stromal fragments were greater with a larger needle size. Numbers of stromal fragments and bipolar naked nuclei were greater in the low fat as compared to the control group but no differences in epithelial cell yield were observed between the two groups. This study confirms that fine needle aspiration biopsy is a feasible method of obtaining epithelial cells from women without discrete breast masses, but suggests that cell proliferation cannot be assessed using Ki-67 and PCNA in such samples.

Patient centered long-term care.

Drawing upon an individual's needs, values, and expectations to guide decisionmaking and care giving is integral to long-term care (LTC). Articles in this issue demonstrate that client values and preferences can be elicited and used to guide decisionmaking about LTC. Service delivery and payment features can be shaped to support the patient/consumer, as well as to support and strengthen her or his informal caregivers. Significant constraints to making LTC more client centered are also identified. Key issues relate to the availability of and methods to process information as well as pressures on provider staff that impede their ability to support clients and their families. More broadly, access to appropriate LTC services is being shaped by programmatic shifts and legal forces that may enhance or impede the ability to place patients/clients at the center of LTC.

Squamous cell carcinoma of the breast.

OBJECTIVE: To review the mammographic and ultrasonographic features of primary breast cancer containing squamous cell carcinoma. PATIENTS AND METHODS: From medical records for breast cancer patients seen over a 37-year period the authors identified 19 patients with squamous cell carcinoma, for 5 of whom histologic sections and imaging studies were available. The tumours were classified on the basis of histologic findings as pure (in two patients) or predominantly (in three patients) squamous cell carcinoma. Mammograms were available for four of the patients, and the mammographic report only was available for analysis for the fifth. Ultrasonography had been performed for four of the patients; the images were available for two of the patients and the reports only for two. RESULTS: The median age of the patients was 55 years. The mean size of the tumours, all of which were palpable, was 5.0 cm. None of the tumours was connected to the skin, arose in the nipple-areolar complex or was metastatic. On mammography, the margins of all five masses, which were oval in shape, were indistinct and partly well-circumscribed; in three cases, the tumour margin was also partly spiculated. No malignant microcalcifications were seen. The two "pure" squamous cell carcinoma tumours appeared on ultrasonography as solid hypoechoic masses, and two of the predominantly squamous cell carcinoma tumours had both cystic and solid components. At gross pathological examination, four of the tumours (two "pure" and two predominantly squamous cell carcinoma) were cystic, which reflected areas of necrosis and cyst formation. CONCLUSION: Although "pure" or predominantly squamous cell carcinoma is a rare histologic variant of breast cancer that lacks any typical mammographic features, this tumour can be added to the differential diagnosis of cystic breast masses seen on ultrasonography.

Synthetic extracellular matrix supports healing of mucogingival surgery donor sites.

Palatal donor sites are commonly used in periodontal surgery. Their healing speed determines the patient's comfort. This may be enhanced by the use of collagen sponges, supplemented with various components of the extracellular matrix, which display chemotactic properties and enhance the proliferation and synthesis activity of fibroblasts. A collagen-based dressing supplemented with such extracellular matrix components, including chondroitin 4 sulfate, heparan sulfate, and fibronectin was used, in an attempt to facilitate the healing of donor sites in 10 periodontal patients. Immunohistological techniques were used on biopsy samples from the margin of these volunteer's healing donor sites to appreciate tissue reconstruction around the synthetic material. Our results indicate a fast epithelial growth, neovascularization, and spatial organization of the new matrix. Limited and topographically selective inflammatory reactions, characterized by polymorphonuclears and mononuclear cells seen near the wound's margin, could be responsible for the production of soluble factors supporting reconstruction.

[Evaluation of the Community Periodontal Index of Treatment Needs (CPITN)]. / Evaluation de l'indice des besoins de la collectivité en matière de traitement des parodontopathies (CPITN).

This article consists of a critical analysis of the CPITN, an index based on binary logic and the partial recording of data. The authors discuss the possible loss of information connected with the fact that the data collection covers 6 scores per individual instead of more comprehensive scoring for which there are methods involving several surfaces per tooth. This approach is discussed on the basis of research carried out by the authors and a review of the literature. Moreover, one aspect of the CPITN which often gives rise to controversy is whether recession is pathological or not, and therefore to what extent it should be recorded. This aspect is discussed and analysed. Finally, quantification of the time needed to provide periodontal care is also relevant when using this index, which is the reference index for the WHO Global Oral Data Bank.

A profile of home health users in 1992.

Recently, the use of home health services by Medicare beneficiaries has been growing. From 1987 to 1992, the percentage of all enrollees receiving home health rose from 4.8 to 7.2 percent, while the average number of visits among users increased from 23 to 54. This article uses the 1992 Medicare Current Beneficiary Survey (MCBS) to profile home health users. In addition to providing descriptive information about who uses Medicare home health, Tobit models are estimated to determine the factors that predict home health utilization and reimbursement. Various policy options for redesigning the home health benefit are also discussed.

The Medicare home health initiative.

This article describes the Medicare home health benefit and summarizes growth and change in the use of the benefit and in the industry providing home health care. The article also details the organization and goals of the Home Health Initiative, describes its four key components--quality assurance (QA), administration, policy, and research-and concludes with a discussion of the status of the Initiative.