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Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 217 records · Page 12Linked to original sources
PubMed1995

Bacteriolytic activity caused by the presence of a novel lactococcal plasmid encoding lactococcins A, B, and M.

Lactococcus lactis subsp. lactis biovar diacetylactis DPC938 was identified as a bacteriocin-producing strain which exhibited a bacteriolytic effect on other lactococci. Lysis of such target strains was associated with decreases in optical density and release of the intracellular enzyme lactate dehydrogenase. DPC938 exhibits cross-immunity to L. lactis subsp. cremoris 9B4 (M.J. van Belkum, B.J. Hayema, A. Geis, J. Kok, and G. Venema, Appl. Environ. Microbiol. 55:1187-1191, 1989), a strain which produces the bacteriocins lactococcins A, B, and M. Genetic analyses revealed that a 15.5-kb region of DNA encoding these bacteriocins is highly conserved in 9B4, DPC938, and DPC3286, an overproducing derivative of DPC938. This region is located on a 72- and a 78-kb nonmobilizable plasmid in DPC938 and DPC3286, respectively. The bacteriolytic effect exhibited by DPC938 and DPC3286 on sensitive cultures is most probably due to the concerted action of all three bacteriocins. Since these cultures exhibit a lytic effect on lactococci, they have a potential application in the dairy industry as accelerators of starter lysis and hence accelerators of cheese ripening.

Amino Acid Sequence↗
PubMed1994

Evidence for involvement of tyrosine phosphorylation in taxol-induced apoptosis in a human ovarian tumor cell line.

Taxol is an antineoplastic agent with significant activity against ovarian as well as breast cancer. To investigate mechanisms by which taxol exerts its cytotoxic action, taxol-induced apoptosis, characterized by morphologic changes and internucleosomal DNA fragmentation, was examined in a human ovarian tumor cell line. Time-dependent morphologic changes, characteristic of apoptosis, were observed over the same time as the appearance of internucleosomal DNA fragmentation. The specific protein tyrosine kinase inhibitors genistein and herbimycin A, and the ATP depletion agent sodium azide, interfered with taxol-induced DNA fragmentation and clonal cell death. Based on a quantitative reverse transcription-polymerase chain reaction technique, bcl-2 alpha oncogene expression was decreased in conjunction with taxol-induced DNA fragmentation, and this decrease could be blocked by genistein. These results strongly implicate protein tyrosine phosphorylation as an event that mediates apoptosis and, thus, the antitumor activity of taxol in ovarian cancer.

Apoptosis↗
PubMed1994

Expression of phytochrome apoprotein from Avena sativa in Escherichia coli and formation of photoactive chromoproteins by assembly with phycocyanobilin.

Phytochrome DNAs from oat (Avena sativa L.) encoding the full-length 124-kDa polypeptide, a 118-kDa fragment lacking the first 65 amino acids, and two N-terminal fragments of 65 kDa and 45 kDa were subcloned and expressed in Escherichia coli. Reducing the temperature to 25 degrees C during cell growth and the coexpression of chaperones improved the folding into a functional conformation for most of the polypeptides, and in one case the yield of polypeptides was also enhanced. A maximum yield of reconstitutable apoprotein was obtained by expressing the 65-kDa fragment consisting of 595 amino acids. The apoproteins could be assembled in the dark with phycocyanobilin into photoreversible chromoproteins. The yield of photoreversible pigment could be further increased by far-red/red irradiation cycles, indicating that the presence of the chromophore promotes the correct folding of the binding site. The chromoproteins with an intact N-terminal domain exhibit Pr and Pfr absorption bands, which are blue-shifted relative to the corresponding bands of native phytochrome due to the particular phycocyanobilin structure. The 118-kDa fragment, only lacking the 6-kDa N-terminus, exhibits a strong Pr band, but only a weak Pfr absorbance. This indicates an essential role of the front 6-kDa region of the protein in the formation of the far-red absorbing chromophore-protein complex. Otherwise, the C-terminal region seems to be less important for photoreversibility as indicated by the function of the shorter fragments.

Base Sequence↗
PubMed1994

IAIMS and sharing.

The Integrated Academic Information Management System (IAIMS) concept is about sharing resources and information, and about improving the decision-making ability of health care professionals by integrating information. At Columbia-Presbyterian Medical Center, the IAIMS project has established an information architecture based on common, shared computing and networking resources. The institutional computing culture has been changed with increased sharing of information and, consequently, improved quality of information. Several classes of information in the areas of clinical, scholarly, administrative, basic research, and core resources have been identified for better understanding of information responsibility. Technical problems such as heterogeneity on workstation platforms and lack of universal syntactic and semantic standards for health care information exchange still impede inter-institutional sharing of information.

Artificial Intelligence↗
PubMed1994

[How to measure the risk of breast cancer in a population?].

One can read that one woman in 11 in France and one in nine in the USA will get breast cancer. This high risk is the result of the irrealistic assumption that all women remain exposed to the risk of breast cancer until age 90, and ignores the risk of death before that age. It is possible to allow for the occurrence of death before age 90. We describe the method, and find a risk of getting breast cancer before age 90 of one in 14 in France. The estimation of the risk of breast cancer over limited periods of life may also be useful. We describe how these estimates can be obtained, and present some results. For instance the risk of breast cancer between age 50 and 69 is one in 29, and the risk between 50 and 79 is one in 19.

Adolescent↗
PubMed1993

The protein kinase mos activates MAP kinase kinase in vitro and stimulates the MAP kinase pathway in mammalian somatic cells in vivo.

The mos protooncogene encodes a serine/threonine protein kinase that is only expressed at significant levels in germ cells. Recombinant malE-mos protein (Xenopus mos protooncogene fused in frame to the maltose binding protein of E. coli) activates MAP kinase in cell-free extracts prepared from Xenopus oocytes and eggs. Here we show that malE-mos immunoprecipitates from Xenopus extracts phosphorylate and activate MAP kinase kinase in vitro, indicating that mos can function as a MAP kinase kinase kinase. Moreover, ectopic expression of mos in mammalian somatic cells, that lack any endogenous mos protein, triggers the activation of MAP kinase in vivo. These results identify the mos protooncogene as a direct activator of the MAP kinase pathway, with the potential to activate this kinase cascade even in cells where normally there is no expression of mos.

3T3 Cells↗
PubMed1993

[Mortality from tobacco use].

The health consequences of tobacco smoking can be estimated from tobacco consumption data, mortality statistics and estimates of risks observed among populations of smokers in cohort studies. In 1990, 60,000 deaths were attributable to smoking in France, corresponding to more than 10% of all deaths. The effect of smoking is much greater in the male (55,000 deaths) than in the female population (5,000 deaths). It is in the age group 45 to 64 that tobacco has the largest effect, contributing to 28% of all deaths in the male population. The health effects observed in 1990 are the consequences of habits which were adopted 20, 30 or 40 years ago. Because the consumption of cigarettes increased regularly between 1950 and 1976, and remained stable since, one can predict that the number of tobacco related deaths will increase for several more decades. This increase will be largest in the female population, and what is already seen in the USA: more women dying from lung cancer than from breast cancer, will one day be seen in France. Despite anti-smoking activities, there is no marked reduction in tobacco sales, and the decrease in the relative price of cigarettes observed between 1960 and 1980, will not be completely compensated by the increases planned for 1993.

Adolescent↗
PubMed1993

Resistance to methicillin and virulence of Staphylococcus aureus strains in bacteriemic cancer patients.

OBJECTIVE: To estimate the relation between resistance to methicillin and virulence in strains of Staph. aureus by estimating the survival at day 30. DESIGN: Case control analysis. SETTING: Inpatients at a major Cancer Referral Center. PATIENTS: 21 patients with methicillin-resistant Staph. aureus (MRSA) bactaeremia and 45 patients with methicillin-susceptible Staph. aureus (MSSA) bactaeremia, all treated with vancomycin. MEASUREMENTS AND MAIN RESULTS: Fewer MRSA than MSSA patients were neutropenic (p = 0.04), but more MRSA patients were hospitalized in intensive care units (p = 0.03), had had surgical episodes (p = 0.06). MRSA patients also had more microbiological samples cultured (p = 0.007). The outcome of the bacteriemic episodes in 14 MRSA and 14 MSSA patients matched for these four factors showed that blood cultures from MRSA patients remained positive significantly longer (p = 0.04), but that survival and length of hospital stay were not significantly different. CONCLUSIONS: These results do not indicate that methicillin-resistance in Staph. aureus is associated with increased virulence.

Adolescent↗
PubMed1993

Growth hormone response to clonidine in neuroleptic-free patients with multidagnostically defined schizophrenia.

The role of alpha 2-adrenergic receptor sensitivity in schizophrenia was examined by measuring growth hormone (GH) response after the intravenous administration of clonidine (1.3 micrograms/kg) in 26 healthy control subjects and 26 neuroleptic-free, acutely psychotic patients with at least 1 out of 11 possible diagnoses of schizophrenia derived from a multidiagnostic psychopathological assessment. GH responses were significantly (0.01) lower than control values in schizophrenias defined by E. Bleuler, M. Bleuler, Schneider, Langfeldt, Taylor and Abrams, and Cloninger, but not in DSM-III, World Health Organization, Feighner, Kraepelian, and Research Diagnostic Criteria (RDC) schizophrenias. Eight patients with RDC schizoaffective disorder also had a blunted response. However, there were no correlations with any symptom measures. There were no differences between paranoid and nonparanoid patients, although there was a significant difference between nonparanoid patients and control subjects. These findings support the presence of noradrenergic dysfunction in some patients within the schizophrenia syndrome, possibly those whose illnesses have an affective component. The study also illustrates the need for simultaneous investigation of several different sets of diagnostic criteria for schizophrenia in neurobiological research.

Adolescent↗
PubMed1993

Effectiveness of a dapsone compliance program in leprosy.

BACKGROUND: Long-term effectiveness of a dapsone compliance program was assessed in patients with leprosy. METHODS: The monitoring program consists of urine dapsone/creatinine ratio determination at each visit with subsequent patient feedback and education. Eighty-eight patients receiving dapsone and seen in a leprosy clinic from 1985-1990 were included. RESULTS: The proportion of patients compliant with dapsone during a given year ranged from 70.0% (1987) to 94.4% (1989). Overall compliance for the 6-year period was 81.6%. This level of compliance was significantly different (P < 0.05) than the baseline compliance in the leprosy clinic of 46.7%. CONCLUSIONS: Compliance monitoring, combined with active patient involvement, was effective in sustaining high compliance over a 6-year period.

Adult↗
PubMed1993

Effect of Increasing the Copy Number of Bacteriophage Origins of Replication, in trans, on Incoming-Phage Proliferation.

Bacteriophage resistance mechanisms which are derived from a bacteriophage genome are termed Per (phage-encoded resistance). When present in trans in Lactococcus lactis NCK203, Per50, the cloned origin of replication from phage phi50, interferes with phi50 replication. The per50 fragment was found to afford negligible protection to NCK203 against phi50 infection when present in a low-copy-number plasmid, pTRK325. A high-copy-number Per50 construct (pTRK323) dramatically affected phi50 infection, reducing the efficiency of plaquing (EOP) to 2.5 x 10 and the plaque size to pinhead proportions. This clone also afforded significant protection against other related small isometric phages. Per31 was cloned from phage phi31 and demonstrated to function as an origin of replication by enabling replication of per31-containing plasmids, in NCK203, on phi31 infection. A low-copy-number Per31 plasmid (pTRK360) reduced the EOP of phi31 on NCK203 to 0.3 and the plaque diameter from 1.5 to 0.5 mm. When this plasmid was cloned in high copy number, the EOP was further reduced to 7.2 x 10 but the plaques were large and contained Per31-resistant phages. Characterization of these "new" phages revealed at least two different types that were similar to phi31, except that DNA alterations were noted in the region containing the origin. This novel and powerful abortive phage resistance mechanism should prove useful when directed at specific, problematic phages.

Journal Article↗
PubMed1993

Therapeutic monitoring and pharmacist intervention in a Hansen's disease clinic.

OBJECTIVE: To describe the role of the clinical pharmacist in a Hansen's disease (HD, leprosy) clinic and to describe the development, validation, and operation of a dapsone compliance monitoring program. RATIONALE: HD remains a major, worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD; however, high rates of noncompliance with this agent have been reported by many treatment centers. The assessment of compliance in HD patients is important to help distinguish between treatment failure secondary to noncompliance or to the development of resistance. SETTING: In the US, the Chicago Regional Hansen's Disease Center at the University of Illinois at Chicago is one of ten centers that provide comprehensive care to patients diagnosed with this condition. This article reviews the clinical pharmacy services and dapsone compliance program in the clinic encompassing the years 1983-93. RESULTS: The clinical pharmacist provides a variety of clinical services in the clinic as well as coordinating the clinical research program. A pharmacist-generated dapsone compliance program led to improvement in compliance rates and clinical outcome. This improvement in compliance has been sustained over an extended period of time. CONCLUSIONS: The clinical pharmacy services performed in the HD clinic provide a model for pharmacy involvement in other chronic disease states. The dapsone compliance program has been successful in improving patient care and obtaining reimbursement for clinical pharmacy services.

Academic Medical Centers↗
PubMed1993

Medicaid beneficiaries and health reform.

Some health reform proposals include reductions in Medicaid benefits in favor of a more basic health plan that would cover a broader range of Americans, including the uninsured. This study provides data on the implications of such proposals. With current Medicaid coverage, the study finds that one in five adults experienced serious problems getting and paying for health care in the past year. In addition, a substantial number of Medicaid beneficiaries now have trouble paying for the basic necessities of life; the well-being of these beneficiaries (between one-quarter and one-half of all beneficiaries) would be placed in jeopardy by proposed cuts in coverage levels and benefits. Medicaid beneficiaries report worse health status and greater disability level than the general public, suggesting that proposals to link Medicaid coverage with ability to work should be pursued with caution.

Adult↗
PubMed1993

[Should comparison be made between survival of responding vs. non-responding patients?].

In oncology trials, it is not uncommon to compare the survival of the patients who responded to therapy to the survival of the non-responders, while choosing the beginning of therapy as time 0. This comparison is biased because part of the survival time of the responders is the time between the start of therapy and response, which is guaranteed by the observation of the response. The survival experience of responders must be studied starting from the observation of response. A significant difference between the survival experiences of responders and non-responders is often considered as evidence of a causal relation between response and better survival, or even as demonstrating the efficacy of the treatment. A causal relation between response and survival is certainly biologically plausible but the response may as well be associated with some prognostic factors, the selection of responders leading to the selection of patients with a better prognosis, independently of the treatment. The conclusion that the efficacy of the treatment is demonstrated assumes that the non responders, which represent treatment failures, are a control group which can be compared to the responders. This is absolutely untenable, because the two groups are likely to be very different.

Combined Modality Therapy↗
PubMed1993

[Prognostic value of a continuous variable and an optimal cutoff point].

To study the prognostic value of a continuous variable, cathepsin D in breast cancer, for example, it has been suggested to consider all the divisions of the population in two groups obtained by changing the cutoff level for cathepsin D, and to select the division leading to the largest difference in survival between the two groups. This method, called optimized cutoff point is statistically incorrect as currently used, and requires corrections. Moreover, the optimised cutoff point will be different in different groups of patients, and has no interpretation either biologically or statistically. Continuous prognostic factors should be studied by dividing the population in more than two groups, in order to examine the shape of the relation between the factor and survival. The limits used to define the groups should not depend on the observed survival in the groups.

Breast Neoplasms↗
PubMed1992

Plasmid involvement in the formation of a spontaneous bacteriophage insensitive mutant of Lactococcus lactis.

Lactococcus lactis subsp. lactis biovar. diacetylactis DPC721 is a spontaneous bacteriophage insensitive mutant of strain DPC220, isolated after challenge with an industrial bacteriophage, phi D1. Plasmid analysis demonstrated that the bacteriophage insensitivity was associated with the absence of two native DPC220 plasmids (pAH82 and pAH33), and the presence of a novel plasmid (pAH90) in DPC721. The plasmids were transferred by conjugative mobilization to a plasmid free background where it was confirmed by restriction mapping that pAH90 is a co-integrate formed by the precise recombination of pAH82 and pAH33. The resistance phenotype encoded by pAH90 was also active against two bacteriophage homologous for the plasmid-free strain. Plasmid pAH90 was shown to encode at least two independent resistance mechanisms, including an adsorption-inhibition mechanism and a restriction and modification system. The adsorption-inhibition mechanism encoded by the co-integrate plasmid was specific for one of the phage used in this study.

Bacteriophages↗