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Biomedical subjects

J W Winkelman

Publications and source records attributed to J W Winkelman.

At least 19 recordsLinked to original sources
PubMed1995

Total serum calcium reference intervals in postmenopausal outpatients.

The distribution of values of serum calcium has been studied in the following four outpatient populations: premenopausal (n = 411) and postmenopausal women (n = 399), men less than 50 years old (n = 365) and men over 55 years old (n = 361). Their respective average total serum calcium values (mg/dl) were 9.42, 9.56, 9.53, and 9.45. The reference intervals derived for total serum calcium (mg/dl) were 8.4-10.3 (premenopausal women), 8.4-10.7 (postmenopausal women), 8.6-10.5 (men less than 50 years old), and 8.4-10.4 (men over 55 years old). Increased total serum calcium levels were observed in the postmenopausal women as compared with both premenopausal women (p < 0.001) and with men over 55 years old (p < 0.003). Eight percent of the values obtained in postmenopausal women were above the current reference interval, as compared to 1.7% in premenopausal women, and 3.3% in men over 55 years old. In conclusion, the age-related increase in total serum calcium in postmenopausal female outpatients warrants a higher upper limit of the reference interval for this subpopulation.

Calcium↗
PubMed1995

Evolution beyond the shared services model of consolidated hospital clinical laboratories.

OBJECTIVE: To compare the operational and financial outcomes of the transition from shared laboratory services to a recentralized model, in a consolidated hospital system. SETTING: United Health Services Hospitals (Binghamton General, Wilson Memorial, and Ideal hospitals, New York State). INTERVENTION: Consolidation of hospital services and recentralization of laboratory testing to a single site (Wilson Memorial Hospital). MAIN OUTCOME MEASURES: Laboratory workload, testing efficiency, personnel and nonpersonnel expenses, analytic error rate, turnaround time, and proficiency-testing scores. RESULTS: The postintervention period (1988 to 1992) was characterized by a 51% and a 10% increase in the out- and inpatient workloads, respectively, with a concomitant 24% increase in testing efficiency. The salary expenses were 26% lower, while the total true cost savings ranged from $1,544,000 (11.6%) to $2,500,000 (21.9%) compared with the shared services model. The recentralization produced decreased analytic error rates and improved testing turnaround time. CONCLUSIONS: The total costs per test have been lowered in the recentralized model. Recentralization may provide further true cost savings over the shared services model while maintaining high-quality service.

Cost Control↗
PubMed1994

A predictive model for fetal lung maturity employing gestational age and test results.

Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude false-negative predictions of absence of respiratory distress syndrome (RDS), with a reciprocal low predictive value for maturity. The authors employed FLM Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model for FLM that included the obstetric estimates of gestational age. The charts of 388 newborns were abstracted and reviewed. The clinical outcome was the gold standard of the multivariate logistic analysis. Both the obstetric estimates of gestational age and the test result were significant predictors of the clinical outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS as a function of both of these variables allows for adjustment of the test cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A result for different gestational ages. Fetal lung maturity probability reporting may facilitate clinical decision-making.

Albumins↗
PubMed1992

DNA topology-mediated regulation of transcription initiation from the tandem promoters of the ilvGMEDA operon of Escherichia coli.

It is becoming increasingly clear that the intrinsic and protein-induced topological properties of the DNA helix influence transcriptional efficiency. In this report we describe the properties of two upstream activating regions that influence transcription from the non-overlapping tandem promoters of the ilvGMEDA operon of Escherichia coli. One 20 base-pair region between the promoter sites contains an intrinsic DNA bend that activates transcription from the downstream promoter. The other region contains an integration host factor (IHF) binding site that overlaps the upstream promoter site. IHF binding at this site represses transcription from the upstream promoter and enhances transcription from the downstream promoter. IHF also induces a severe bend in the DNA at its target binding site in the upstream promoter region. The activating property of the 20 base-pair DNA sequence located between the promoters is dependent upon the helical phasing of the sequence-directed DNA bend that it encodes. However, the IHF-mediated activation of transcription is not dependent upon the helical phasing (spatial orientation) of the upstream IHF and downstream promoter sites. The IHF-mediated activation of transcription is also uninfluenced by the presence or absence of the intrinsic DNA bend between its binding site and the downstream promoter site. These results suggest the interesting possibility that IHF activates transcription from the nearby downstream promoter simply by bending the DNA helix in the absence of specific IHF-RNA polymerase or upstream DNA-RNA polymerase interactions.

Bacterial Proteins↗
PubMed1992

Synergistic effects of photoactivated tetra(4-sulfonatophenyl)porphine and nocodazole on microtubule assembly, accumulation of cells in mitosis and cell survival.

Human carcinoma cells of the line NHIK 3025 were incubated with meso-tetra(4-sulfonatophenyl)porphine (TPPS4) for 18 h and exposed to light in the absence or presence of nocodazole. Nocodazole (1 microgram ml-1) was applied to the cells 15 min prior to light exposure and washed off the cells immediately afterwards. The presence of nocodazole during photoactivation of TPPS4-loaded cells leads to a significantly reduced ability of tubulin to repolymerize after withdrawal of nocodazole, an increased accumulation of the cells in mitosis with a larger fraction in c-metaphase and a higher yield of photoactivated cells. A higher proportion of the cells accumulating in mitosis 6-12 h after exposure to light is unable to form colonies when exposed to light in the presence of nocodazole than in its absence. The present results are consistent with a specific TPPS4-induced photodamage to the unpolymerized form of the microtubule components.

Carcinoma in Situ↗
PubMed1991

Downstream outcomes: using insurance claims data to screen for errors in clinical laboratory testing.

A methodology is described by which health insurance claims data might be used to discover the occurrence of systematic errors by clinical laboratories. False-positive results should generate a series of tests or treatments that are eventually abandoned as the false signal of the initial test is discovered while false-negative results may cause necessary tests or treatments to be unduly delayed. False results may also generate adverse outcomes such as an unusually high number of deaths or hospitalizations among persons who have received particular laboratory tests. Health insurance claims data may be used to discover these patterns and how the inclusion of laboratory results on claims would improve the precision of such inferences. Appropriate statistical tests are discussed.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1991

Light induced relocalization of sulfonated meso-tetraphenylporphines in NHIK 3025 cells and effects of dose fractionation.

Human cervix carcinoma cells of the line NHIK 3025 were incubated for 18 h with sulfonated meso-tetraphenylporphines (TPPSn where n = 1, 2a, 2o or 4) followed by 1 h in sensitizer-free medium and then exposed to light. The fluorescing fraction of TPPS4, TPPS2o and TPPS2a has recently been shown to be located intracellularly in extracellular granules which are intracellularly localized in a similar pattern as acridine orange-stained granules, assumed to be endosomes and lysosomes (Berg, K., A. Western, J. Bommer and J. Moan. Photochem. Photobiol. 52, 481-487). Light exposure induced a relocalization of TPPS4 from its granular pattern to mainly the nuclear area while TPPS2o and TPPS2a relocalized mainly to cytoplasmic areas. After the light-induced relocalization TPPS4 became less efficient in sensitizing photoinactivation of cells as measured per fluorescing cellbound TPPS4 molecules while TPPS2a and TPPS2o became more efficient. These changes were independent of the extracellular concentration of TPPSn applied to the cells, except for cells incubated with 75 micrograms/mL TPPS4. These cells became more sensitive to light after a light exposure inactivating 20% of the cells. This increased photosensitivity seems to be related to a 2-2.5 fold increase in the amount of fluorescing cellbound TPPS4 induced by the first light exposure.

Biological Transport↗
PubMed1991

Cost savings in a hospital clinical laboratory with a pay-for-performance incentive program for supervisors.

A pay-for-performance incentive program for clinical laboratory supervisors was developed and implemented at Brigham and Women's Hospital (Boston, Mass). It provides monetary rewards to personnel who directly produce cost savings in their area of responsibility. This reward system is new to the hospital laboratory but is commonly used in industry. Substantial true cost savings over and above previously established stringent budgets were achieved, 11% of which was returned to first-line supervisors in the form of a bonus. The program expanded the scope of professionalism for supervisors to include fiscal management.

Cost Control↗
PubMed1990

Characterization of the integration host factor binding site in the ilvPG1 promoter region of the ilvGMEDA operon of Escherichia coli.

The ilvGMEDA operon of Escherichia coli, which encodes four of the five enzyme activities required for the biosynthesis of isoleucine and valine, is preceded by tandem promoters ilvPG1 and ilvPG2 which are separated by 72 base pairs. While both of these promoters are transcriptionally active in vitro, only the operon proximal promoter, ilvPG2, is transcriptionally active in vivo, and upstream DNA sequences encoding the ilvPG1 promoter region enhance the in vivo transcriptional activity of the ilvPG2 promoter 60-fold. The binding of the integration host factor protein (IHF) to this upstream region (Tsui, P., and Freundlich, M. (1989) J. Mol. Biol. 203, 817-820) has been shown to repress transcription from the ilvPG1 promoter both in vivo and in vitro (Pereira, R. F., Ortuno, M. J., and Lawther, R. P. (1988) Nucleic Acids Res. 16, 5972-5989). Furthermore, E. coli strains deficient for IHF are compromised for isoleucine and valine biosynthesis (Friden, P., Voelkel, K., Sternglantz, R., and Freundlich, M. (1984) J. Mol. Biol. 172, 573-579). Therefore, in order to further understand this repressor/activator role of IHF, we have undertaken a detailed analysis of the interaction of IHF with the DNA sequences in the ilvPG1 promoter region. The results of hydroxyl radical footprinting, dimethyl sulfate protection, and ethylation interference experiments show that IHF binds to a target site that overlaps the ilvPG1 promoter region. The results of these experiments also demonstrate that IHF interacts primarily with the minor groove of the DNA helix and that the IHF target site in the ilvPG1 promoter region shares a high degree of DNA sequence identity with other high affinity IHF target sites involved in DNA replication and site-specific recombination.

Bacterial Proteins↗
PubMed1990

Cellular inhibition of microtubule assembly by photoactivated sulphonated meso-tetraphenylporphines.

This work relates to studies on modes of phototoxicity by sulphonated mesotetraphenylporphines on cultured cells. Toxicity appears to be related to inhibition of microtubule function. Treatment of human cervix carcinoma cells of the line NHIK 3025 incubated for 18 h with meso-tetraphenylporphine sulphonates (TPPSn where n = 2a, 2o or 4) and exposed to light, inhibits multiplication for the first hours after light exposure, a significant fraction of the cells accumulating in mitosis. The maximal number of cells in mitosis after treatment (approximately 20%) is dependent on the fluence but is similar for all three photosensitizers. For the first hours after treatment the mitotic cells were always mainly in metaphase; mainly seen as c-metaphases and three-group metaphases. During this time anaphase and telophase cells were absent or greatly reduced in number. Indirect immunofluorescence staining of beta-tubulin showed that the spindle apparatus of mitotic cells was perturbed in all cases. Results are presented which indicate that photoactivation of TPPSn located on the plasma membrane destroys microtubules in interphase cells and leads to arrest of the cells in mitosis. The localization of the dye which sensitizes the photoinduced perturbation of microtubules is further discussed.

Cell Division↗
PubMed1990

Cellular uptake and relative efficiency in cell inactivation by photoactivated sulfonated meso-tetraphenylporphines.

The cellular uptake, relative fluorescence quantum yields and photosensitizing efficiencies of meso-tetraphenylporphines sulfonated to different degrees (TPPSn) have been investigated using the human carcinoma cell line NHIK 3025. The efficiencies of these dyes in photoinactivation of cells were highly dependent on the number of sulfonate groups on the derivatives. These differences in phototoxicity were primarily due to different abilities to be taken up by cells, but were also dependent upon the cellular localization of the dyes. TPPS1 and TPPS2a were more efficiently taken up by the cells than TPPS2o and TPPS4. Plasma membrane associated TPPS4 was less efficient in cell inactivation per quantum of fluorescence emitted than intracellularly located dye. This was also to some extent the case for TPPS1 but not for TPPS2a and TPPS2o. The results presented here indicate that TPPS2a and TPPS1 are the most promising of the TPPSns for possible future use in photodynamic therapy.

Cell Survival↗
PubMed1989

Electrochemical method for measuring C-reactive protein using crown ether--phosphate ester ionophores.

A new electrochemical method for measurement of C-reactive protein (CRP) is presented. We have synthesized new crown ether-phosphate ester ionophores having high affinity for CRP. A study using proton nuclear magnetic resonance shows CRP binding to the ionophores in stoichiometric amounts. The incorporation of these crown ether-phosphate ester ionophores into poly(vinyl chloride) membrane electrodes yields a CRP-sensitive electrode with sensitivity in the microgram per milliliter range. The ionophore synthesis and preliminary electrode characteristics are described.

C-Reactive Protein↗
PubMed1988

Use of "average of normals" quality control procedure in the detection and resolution of assay discrepancies.

Improved computer technology and imperatives for cost control have made the use of "average of normals" (AVON) procedure an attractive alternative to the more expensive standard quality control programs for clinical laboratory assay monitoring. The authors report the use of a version of the AVON procedure to resolve assay discrepancies with CO2 determination that the traditional quality control program appeared incapable of detecting. Their study suggests that the mean of patients within the reference interval (RI) is a sensitive indicator of accuracy, whereas the percentage of patients within RI is a good indicator of random imprecision.

Carbon Dioxide↗
PubMed1987

Toxic and phototoxic effects of tetraphenylporphinesulphonate and haematoporphyrin derivative in vitro.

The toxic and phototoxic effects of tetraphenylporphinesulphonate (TPPS4) and haematoporphyrin derivative (HpD) have been examined in vitro. TPPS4 was found to have less dark toxicity to the cells than HpD as measured by inhibition of cell multiplication and colony formation at comparable extracellular concentrations. TPPS4 was also less effective than was HpD in photoinactivating NHIK 3025 cells by more than a factor 2 which should be expected on the basis of cellular uptake. Spectrofluorometric data suggest that HpD in cells interacts more with lipids than TPPS4. This might explain the large photosensitizing effect of HpD compared to TPPS4 since the lifetime of singlet oxygen is about a factor of 10 longer in a lipid environment than in an aqueous environment. The uptake of TPPS4 and HpD by cancer cells in vitro does not correlate with previous in vivo data, indicating retention of TPPS4 in the tumour stroma. This makes in vitro/in vivo extrapolation difficult with regard to the use of TPPS4 as an agent for photodynamic therapy.

Biological Transport↗
PubMed1986

Viral and bacterial organisms associated with acute pharyngitis in a school-aged population.

To investigate the causes and clinical characteristics of acute pharyngitis among school-aged children (4 to 18 years), we obtained throat cultures for respiratory viruses, Mycoplasma pneumoniae, group A streptococcus, and Chlamydia trachomatis from 320 patients with sore throat and 308 controls without respiratory complaints. The study was conducted from January to April 1985 in a private pediatric practice in central New York State. Sixty percent of the patients and 26% of the control subjects had positive cultures for at least one organism. Forty percent of patients had positive cultures for group A streptococcus, compared with 11.9% of the controls. Fifty (16%) patients had positive viral cultures, compared with eight (2.6%) controls; the predominant viral isolate was influenza A Philippines. Patients infected with influenza A were significantly more likely to complain of cough and hoarseness, and were less likely to have pharyngeal exudate or tender cervical adenopathy, than were patients who had positive cultures for group A streptococcus. Although 49 (15.8%) patients with acute pharyngitis had cultures positive for M. pneumoniae, 53 (17.6%) asymptomatic controls were also had M. pneumoniae-positive cultures. Thus detection of M. pneumoniae in the throat of school-aged children with pharyngitis may not be sufficient to establish a diagnosis of disease caused by this organism. C. trachomatis was not isolated from any patient or control.

Acute Disease↗