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Biomedical subjects

S Hipp

Publications and source records attributed to S Hipp.

9 recordsLinked to original sources
PubMed2007

Quantitative protein analysis from formalin-fixed tissues: implications for translational clinical research and nanoscale molecular diagnosis.

Owing to its cross-linking effects, it is currently believed that formalin fixation of routinely processed tissues in the clinic prevents protein extraction and profiling. The aim of our study was to develop a robust, fast, standardized, and easy to use technique for the solubilization of non-degraded, full length, and immunoreactive proteins from formalin-fixed tissues for western blot and protein microarray analysis. Sections of routinely processed formalin-fixed and paraffin-embedded tissues of various origin were analysed. After deparaffination, tissues were manually dissected from the slides and transferred into an optimized protein extraction buffer system. Proteins were solubilized and subsequently analysed by western blot and reverse phase protein microarrays. We succeeded in isolating non-degraded, soluble, and immunoreactive proteins from routinely processed formalin-fixed tissues. We were able to detect membrane, cytoplasmic and nuclear proteins at the expected molecular weight. No differences were found in the protein yield and protein abundances between fresh frozen and formalin-fixed tissues. Using western blots and reverse phase protein microarrays, the receptor tyrosine kinase HER2, an important protein target for antibody based cancer treatment, was reliably measured in formalin-fixed breast cancer biopsy samples when compared with measurement by immunohistochemistry and fluorescence in situ hybridization; remarkably, immunohistochemically equivocal cases (score 2+) can be categorized according to HER2 protein abundance. Our new clinically orientated multiplexed protein measurement system may be generally applicable to determine the relative abundances of known disease-related proteins in small amounts of routinely processed formalin-fixed tissue samples for research and diagnosis. This technique may also be used to identify, characterize, and validate known and new protein markers in a variety of human diseases.

Animals↗
PubMed2006

Clinical proteomics: new trends for protein microarrays.

Protein microarrays are an emerging class of nanotechnology for tracking many different proteins simultaneously. Much progress has been made for applications in basic sciences. Translation of these methods for the treatment of patients, however, is slow, because the realities in the clinic are rarely taken into account, and proteomic changes in cultured cell lines might not fully reflect human diseases due to the lack of the tissue microenvironment. In this review, we summarise current protein microarray approaches that are being developed for profiling tissues and histopathologically defined cell populations from cancer patients. We provide an overview of clinical applications for protein lysate microarrays and discuss the power of this technology for the discovery of disease markers for cancer diagnosis and individualised treatment.

Cell Line, Tumor↗
PubMed2002

Cell cycle progression of chronic lymphocytic leukemia cells is controlled by cyclin D2, cyclin D3, cyclin-dependent kinase (cdk) 4 and the cdk inhibitor p27.

B-CLL cells are arrested in G0/early G1 phase of the cell cycle and are characterized by a marked hyporesponsiveness towards a variety of polyclonal B cell activators. We have previously demonstrated that costimulation with CpG-ODN and IL-2 can overcome this proliferative defect. Cyclin D3 is the principal D-type cyclin which mediates G1 progression in normal B cells, but in B-CLL cells both cyclin D2 and cyclin D3, were strongly upregulated upon stimulation. Both cyclins were associated with cdk4 but not with cdk6, which is the catalytic partner of D-type cyclins in normal B cells. Moreover, immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. The cell cycle inhibitor p27 plays a pivotal role in cell cycle progression of B lymphocytes and has been shown to be overexpressed in B-CLL cells. P27 was rapidly downregulated in B-CLL cells even when stimulated with a non-CpG-ODN or IL-2 alone, while only moderate regulation could be observed in normal B cells. Taken together, our findings demonstrate that regulation of early cell cycle progression differs between B-CLL cells and normal B cells. These findings do not only contribute to the understanding of B-CLL pathophysiology, but might ultimately lead to the identification of new therapeutic targets.

Apoptosis↗
PubMed1999

Assessment of a geographically targeted field intervention on gonorrhea incidence in two New York State counties.

BACKGROUND AND OBJECTIVES: Using study findings that demonstrated the importance of core group members in gonorrhea transmission, in 1984, one New York State county changed its approach toward gonorrhea control by targeting its field intervention activities toward infected persons from a geographic core area. In late 1988, New York State experienced an epidemic increase in the number of syphilis cases. In response, the New York State sexually transmitted disease (STD) control program enacted a Syphilis Initiative, which required the diversion of field staff from gonorrhea to syphilis control activities for a 3-year period. Each of these events held the possibility of impacting gonorrhea incidence in this county. GOAL OF THIS STUDY: To evaluate the impact of core interventions on reducing gonorrhea incidence as compared to traditional nontargeted field intervention methods and to determine the influence on gonorrhea incidence of diverting field activities from gonorrhea to syphilis case finding. STUDY DESIGN: A Poisson regression method was used to estimate gonorrhea incidence for a 22-year period in two similar counties: one county that used core intervention and one that applied traditional case-finding methods. The impact of core intervention was estimated in terms of the reduction in the gonorrhea incidence rate from the preintervention incidence rates. RESULTS: After initiation of the core intervention, the relative risk of gonorrhea decreased by 61%. Between 30 % to 40% of the total reported cases were interviewed for contacts annually during the intervention period. In the control county, the relative risk was reduced by 50% despite a significantly higher percentage of annual case interviews (60%-70%). In addition, a small change in the definition of core (from census tracts encompassing 50% of gonorrhea cases to 30%-35%) during the Syphilis Initiative led to a significant increase (16%) in the relative risk of gonorrhea. CONCLUSION: Targeting partner notification activities toward a geographic core area population appears effective in reducing the risk of gonorrhea, and it was more efficient because the overall percentage of cases interviewed was smaller than in a county using a nontargeted approach. Diversion of staff during a syphilis epidemic, combined with a narrowing of the geographic scope of the core intervention, was associated with an increase in gonorrhea incidence.

Contact Tracing↗
PubMed1993

Risk profile for Chlamydia infection in women from public health clinics in New York State.

The prevalence of chlamydial infection and associated risk factors were studied in 1531 women from ten clinics in New York State excluding New York City. Overall Chlamydia infection rates were 13.6%; 17.6% in eight high risk family planning and STD clinics, and 5.7% in two low risk college and private clinics. Risk factors for Chlamydia infection included: age < 20 years (odds ratio 1.6), use of oral contraceptives (odds ratio 2.0), a history of having more than one sexual partner (odds ratio 1.7) and, in one clinic where data was available, inflammation on Papanicolaou smears (odds ratio 2.1). These data helped secure funding for Chlamydia preventive services and permitted development of a risk profile (score card) of Chlamydia for each age group. Use of such a score card can be most helpful in assigning which patients could benefit most from Chlamydia cultures, especially in those areas where testing is unavailable or too costly to screen all patients.

Adolescent↗
PubMedDate not supplied

A comparative evaluation of bedside capillary blood glucose monitoring devices designed for hospital use.

Capillary blood glucose monitoring devices (CBGMs) that incorporate "wipeless" technology recently have been designed and marketed for hospital use. Our objective was to evaluate three such devices for accuracy and precision, comparing them to a popular device that utilizes older technology and to a reference standard. Blood glucose level was simultaneously determined on the CBGMs and a reference standard. Results were analyzed for precision by performing repeated measurements of a single sample and for accuracy across the entire range of determinations. Clinically relevant subsets of the entire range also were determined and arbitrarily defined as low (< 60 mg/dL), normal (60 to 140 mg/dL), high (141 to 300 mg/dL), and very high (> 300 mg/dL). We found that accuracy and precision of these devices varied considerably. Lack of accuracy was particularly evident upon analysis of the clinically relevant subset ranges of blood glucose levels. Consequently, routine evaluation of CBGMs should include analysis of clinically relevant subset ranges of blood glucose levels. The marked differences in accuracy and precision between CBGMs that are currently.

Adult↗
PubMedDate not supplied

Niacin. I: Dissolution profiles of sustained-release niacin products by automated and manual procedures.

Automated and manual procedures were developed to obtain dissolution profiles of sustained-release niacin formulations. The procedures are based on the United States Pharmacopeia XXII apparatus 1 (basket) at 100 rpm with 900 mL 0.1N HCl as the dissolution medium. Filtered aliquots are read at 260 nm. No interference was found from excipients. The procedures are straightforward and will discriminate between sustained-release and regular niacin formulations.

Biological Availability↗
PubMedDate not supplied

Screening criteria for Chlamydia trachomatis in family planning clinics: accounting for prevalence and clients' characteristics.

The reliability of eight self-reported risk factors as criteria for screening women for Chlamydia trachomatis was evaluated in four family planning clinics in New York State that serve diverse populations. In all, 8,920 women were screened in these clinics; the rates of infection ranged from 2% to 7%. Results of multivariate analyses showed that age was the most important predictor of chlamydial infection in the three clinics where prevalence was 4% or higher; women aged 20-24 were 3-4 times as likely as older women to be infected, and those aged 13-19 were 4-6 times as likely. In these three clinics, screening all women aged 26 or younger (62-80% of the clinic population) would identify about 90% of infected women; in the clinic with the lowest prevalence rate, age was not a reliable criterion. The prevalence of self-reported risk factors varied by clinic, and these factors generally were not reliable indicators of infection. Using the presence of at least one self-reported risk factor as a screening criterion, 80-87% of clinic clients would be screened, and about 90% of infected women would be identified. The presence of clinical signs of chlamydial infection does not increase the reliability of age as a screening criterion.

Adolescent↗