Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 181 records · Page 10Linked to original sources

PubMed1996

Influence of expression system on chromophore binding and preservation of spectral properties in recombinant phytochrome A.

N-Terminal deletion mutants of the plant photoreceptor phytochrome, additionally truncated at two different positions at their C-terminal ends, were expressed both in Escherichia coli and in yeast (Pichia pastoris) and converted into chromoproteins upon chromophore incorporation. The start and end positions of the cDNA employed (phyA from oat) mimic the positions of tryptic cleavage (deletion of the first 64 amino acids, and stop codons after amino acid positions 425 or 595, generating 39-kDa and 59-kDa peptides, respectively. The absorption properties and photochromicity upon red/far-red irradiation of these mutants were compared with their tryptic counterparts derived from native oat phytochrome and with recombinant products possessing intact N-termini, but C-terminal positions identical to those of the corresponding tryptic fragments (45-kDa and 65-kDa peptides). All recombinant 65-kDa and 59kDa peptides bound the chromophore after expression and showed the appropriate absorption spectra of the Pr and the Pfr forms. The smaller chromopeptides (45-kDa and 39-kDa) behaved differently depending on the expression system employed. E. coli-derived peptides exhibited a phytochrome-like difference spectrum only when the intact N-terminus was present (45-kDa product). The recombinant 39-kDa peptide from E. coli was incapable of chromophore binding whereas the identical peptide sequence expressed by P. pastoris formed a chromoprotein with phycocyanobilin. This recombinant phytochrome fragment exhibited a difference spectrum (Pr-Pfr) with an even larger Pfr absorption band than the comparable tryptic 39-kDa fragment. Selectivity of chromophore incorporation and spectral properties suggest that interactions between protein domains of phytochrome control the protein folding and the Pr/Pfr absorption characteristics. Evidently, trypsin digestion down to the 39-kDa fragment affects protein conformation also in terms of Pfr conservation.

Avena↗

PubMed1996

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine.

[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd = 0.50 +/- 0.04 vs. 0.24 +/- 0.02nM; mean +/- S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd = 0.50 +/- 0.07 vs. 0.50 +/- 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.

Adult↗

PubMed1996

Serotonin2 receptors and the serotonin transporter in the schizophrenic brain.

The binding of [3H]paroxetine and [3H]ketanserin to particulate membranes from frontal cortex of subjects who had or did not have schizophrenia was measured as was [3H]paroxetine binding to particulate membranes from the hippocampus and caudate nucleus. There was no change in either the affinity or density of [3H]ketanserin binding to membranes from the frontal cortex of subjects who had schizophrenia. Similarly, there was no difference in the density of [3H]paroxetine binding to membranes from subjects who had or did not have schizophrenia. The affinity of [3H]paroxetine binding in the frontal cortex and putamen did not differ in subjects who had schizophrenia. By contrast, there was a significant decrease in the affinity of [3H]paroxetine binding to the hippocampal membrane from subjects who had schizophrenia (0.40 +/- 0.06 nM vs 0.26 +/- 0.02 nM; p < 0.05). Furthermore, this difference was more apparent in the subjects who had schizophrenia and committed suicide (0.49 +/- 0.09 nM) than it was in those who had schizophrenia but did not commit suicide (0.32 +/- 0.09 nM). As [3H]ketanserin binds to the serotonin2 receptor our data suggest that this receptor is not changed in the Brodmann's area 9 of the frontal cortex. By contrast, [3H]paroxetine binds to the serotonin transporter and therefore our data suggest that the serotonin transporter is altered in the hippocampus of subjects with schizophrenia.

Adolescent↗

PubMed1996

Platelet [3H]dopamine uptake is differentially affected by neuroleptic drug treatment in schizophrenia and schizophreniform disorder.

1. The uptake of [3H] dopamine was measured using platelet-rich plasma (PRP) from neuroleptic-free subjects and again, in some cases, after the subject had been treated with neuroleptic drugs. 2. There were no differences in [3H]dopamine uptake by PRP in subjects who were or were not mentally ill. 3. After treatment with neuroleptic drugs the Km for platelet [3H] dopamine uptake had increased in 76% of subjects with schizophrenia and 87% of subjects with schizophreniform disorder. Similarly, the Vmax for platelet [3H]dopamine uptake had increased in 81% of the subjects with schizophrenia and 86% of the subjects with schizophreniform disorder. 4. By contrast, the Km for platelet [3H]dopamine uptake had decreased in 94% of subjects who had a psychoses associated with an illness other than schizophrenia or schizophreniform-disorder whilst the Vmax for platelet [3H]dopamine uptake also decreased by 94% in these subjects. 5. In subjects with psychoses, platelet [(3)H] dopamine uptake is differentially altered during neuroleptic drug treatment depending on diagnosis.

Adult↗

PubMed1996

Cancer mortality around French nuclear sites.

This study was designed to investigate cancer mortality in the population aged 0 to 64 years residing around the 13 main French nuclear sites in operation before 1985. Five hundred and three communes located within 16 km of the installation were identified and their populations were followed from 1968 to 1989. A total of 8,970,000 person-years of observation was accumulated. The number of cancer deaths and the number of deaths for cancers possibly related to radiation observed in these communes were compared to national mortality rates. There was no difference in overall cancer mortality or in the risk of mortality by cancer site except for breast cancer, for which a deficit was observed in the vicinity of nuclear sites. After correction for the multiplicity of tests, this difference was not significant. Our study showed no excess cancer mortality in the population aged 0 to 64 years residing around French nuclear sites.

Adolescent↗

PubMed1996

Donor insemination: a comparison of lesbian couples, heterosexual couples and single women.

OBJECTIVE: To compare single women, lesbian couples, and heterosexual couples receiving therapeutic donor insemination (TDI). DESIGN: Chart review followed by anonymous mail questionnaires to donor insemination recipients and their partners. SETTING: Infertility clinic in a university hospital. PATIENTS: One hundred fifteen women receiving donor insemination were identified by chart review. RESULTS: Too few single women responded for reliable comparison. Lesbian women were similar to married women in age, education, duration, and outcome of donor insemination. When considering alternatives to TDI, married women were more likely to consider adoption and lesbians were most likely to consider using a known semen donor or having intercourse with a man aware of their desire to have a child. Married couples were less likely to tell others, including the child, about conception by donor insemination. They were also less likely to support disclosing identifying data about the donor to the child. Lesbians were more likely to report stress in their relationships as a result of TDI. Married men were most likely to support mandatory counseling before TDI initiation.

Adoption↗

PubMed1996

Multistage designs for phase II clinical trials: statistical issues in cancer research.

The main objective of phase II clinical trials is to estimate treatment efficacy on a relatively small number of patients in order to decide whether the treatment ought to be studied in large-scale comparative trials. They play a key role in the drug development process, since the results determine whether or not to proceed to phase III trials. Multistage designs for phase II clinical trials proposed by Gehan, Fleming, Simon and Ensign are described and compared. Gehan's and Simon's designs have two stages, Fleming's designs can have two or more stages, and Ensign's three-stage design combines the first stage of Gehan with the two stages of Simon. Phase II clinical trial protocols and reports should include a description of the design selected with a justification for the particular choice. The present practice is very far from this ideal.

Clinical Trials, Phase II as Topic↗

PubMed1996

Use of sequential DTPA clearance and high resolution computerized tomography in monitoring interstitial lung disease in dermatomyositis.

Interstitial lung disease complicating polymyositis-dermatomyositis has a grave prognosis. We report the case of a 50-yr-old woman with dermatomyositis and interstitial lung disease monitored by sequential high-resolution computerized tomography (HRCT) of lung and aerosol clearance times of the radionuclide 99Technetium-diethylene triamine pentacetate (DTPA). She was treated with oral cyclophosphamide and prednisolone with good outcome. Pulmonary response to therapy was followed with sequential HRCT and DTPA scanning. DTPA clearance a measure of lung inflammation, and HRCT paralleled clinical course during the treatment of interstitial lung disease. Sequential HRCT and DTPA were useful adjuncts in the initial assessment and monitoring of interstitial lung disease in association with dermatomyositis.

Anti-Inflammatory Agents↗

PubMed1996

Clinical associations of anti-lamin autoantibodies.

BACKGROUND: The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a number of individual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease. AIMS: To identify the clinical and laboratory associations of anti-lamin autoantibodies in an Australian population. METHODS: Retrospective review of routine antinuclear antibody testing between 1990-1994 for characteristics linear staining of nuclear envelope on indirect immunofluorescence on HEp-2 cells with clinical status defined by retrospective review of case records. RESULTS: Twenty-eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti-cardiolipin antibodies; anti-phospholipid syndrome was present in nine. Seven further patients had liver disease; five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a diverse group of diseases. There was no correlation between the titre of the autoantibody and clinical status. An association with anti-cardiolipin antibodies was found although the cause remains obscure. CONCLUSION: Anti-lamin autoantibodies, as identified by indirect immunofluorescence, are associated with a diverse group of diseases but particularly with anti-phospholipid syndrome and liver disease. Testing for anti-phospholipid antibodies and more specific markers of systemic lupus erythematosus and autoimmune disease, for example anti-dsDNA antibodies, anti-smooth muscle antibodies and anti-mitochondrial antibodies should be pursued when anti-lamin autoantibodies are detected.

Adult↗

PubMed1996

An application in cheddar cheese manufacture for a strain of Lactococcus lactis producing a novel broad-spectrum bacteriocin, lacticin 3147.

Lactococcus lactis DPC3147, a strain isolated from an Irish kefir grain, produces a bacteriocin with a broad spectrum of inhibition. The bacteriocin produced is heat stable, particularly at a low pH, and inhibits nisin-producing (Nip+) lactococci. On the basis of the observation that the nisin structural gene (nisA) does not hybridize to DPC3147 genomic DNA, the bacteriocin produced was considered novel and designated lacticin 3147. The genetic determinants which encode lacticin 3147 are contained on a 63-kb plasmid, which was conjugally mobilized to a commercial cheese starter, L. lactis subsp. cremoris DPC4268. The resultant transconjugant, DPC4275, both produces and is immune to lacticin 3147. The ability of lacticin 3147-producing lactococci to perform as cheddar cheese starters was subsequently investigated in cheesemaking trials. Bacteriocin-producing starters (which included the transconjugant strain DPC4275) produced acid at rates similar to those of commercial strains. The level of lacticin 3147 produced in cheese remained constant over 6 months of ripening and correlated with a significant reduction in the levels of nonstarter lactic acid bacteria. Such results suggest that these starters provide a means of controlling developing microflora in ripened fermented products.

Bacteriocins↗

PubMed1996

The Lactococcal Plasmid pNP40 Encodes a Third Bacteriophage Resistance Mechanism, One Which Affects Phage DNA Penetration.

The lactococcal plasmid pNP40 mediates insensitivity to (phi)c2 by an early-acting phage resistance mechanism in addition to the previously identified abortive infection system, AbiF, in the Lactococcus lactis subsp. lactis MG1614 background. A second abortive infection determinant on pNP40, AbiE, does not confer resistance to (phi)c2. The early-acting mechanism on pNP40 does not prevent phage adsorption nor does it appear to operate by restriction/modification. Phage DNA was not detected in pNP40-containing cells until 30 min following exposure to (phi)c2 compared with 5 min in a sensitive host; however, electroporation of phage DNA into resistant hosts resulted in the release of phage progeny from a dramatically elevated number of cells compared with conventionally infected hosts. It appears therefore that pNP40 encodes a novel phage resistance mechanism which blocks DNA penetration specifically for (phi)c2.

Journal Article↗

PubMed1996

Adaptive acid tolerance response in Listeria monocytogenes: isolation of an acid-tolerant mutant which demonstrates increased virulence.

The ability of Listeria monocytogenes to tolerate low-pH environments is of particular importance because the pathogen encounters such environments in vivo, both during passage through the stomach and within the macrophage phagosome. In our study, L. monocytogenes was shown to exhibit a significant adaptive acid tolerance response following a 1-h exposure to mild acid (pH 5.5), which is capable of protecting cells from severe acid stress (pH 3.5). Susceptibility to pH 3.5 acid is growth phase dependent. Stationary-phase Listeria cultures are naturally resistant to the challenge pH (pH 3.5), while exponential-phase cultures require adaptation at pH 5.5 to induce acid tolerance. Adaptation requires protein synthesis, since treatment with chloramphenicol prevents the development of acid tolerance. Induction of the acid tolerance response also protects L. monocytogenes against the effect of other environmental stresses. Acid-adapted cells demonstrate increased tolerance toward thermal stress, osmotic stress, crystal violet, and ethanol. Following prolonged exposure of L. monocytogenes to pH 3.5, we isolated mutants which constitutively demonstrate increased acid tolerance at all stages of the growth cycle. These mutants do not display full acid tolerance, but their resistance to low pH can be further increased following adaptation to mild-acid conditions. The mutants demonstrated increased lethality for mice relative to that of the wild type when inoculated by the intraperitoneal route. When administered as lower inocula, the mutants reached higher levels in the spleens of infected mice than did the wild type. The data suggest that low-pH conditions may have the potential to select for L. monocytogenes mutants with increased natural acid tolerance and increased virulence.

Acids↗

PubMed1996

Acid adaptation of Listeria monocytogenes can enhance survival in acidic foods and during milk fermentation.

We have previously shown that tolerance to severe acid stress (pH 3.5) can be induced in Listeria monocytogenes following a 1-h adaptation to mild acid (pH 5.5), a phenomenon termed the acid tolerance response (ATR) (B. O'Driscoll, C. G. M. Gahan, and C. Hill, Appl. Environ. Microbiol. 62:1693-1698, 1966). In an attempt to determine the industrial significance of the ATR, we have examined the survival of adapted and nonadapted cells in a variety of acidic foods. Acid adaptation enhanced the survival of L. monocytogenes in acidified dairy products, including cottage cheese, yogurt, and whole-fat cheddar cheese. Acid-adapted L. monocytogenes cultures also demonstrated increased survival during active milk fermentation by a lactic acid culture. Similarly, acid-adapted cells showed greatly improved survival in low-pH foods (orange juice and salad dressing) containing acids other than lactic acid. However, in foods with a marginally higher pH, such as mozzarella cheese, a commercial cottage cheese, or low-fat cheddar cheese, acid adaptation did not appear to enhance survival. We have previously isolated mutants of L. monocytogenes that are constitutively acid tolerant in the absence of an induction step (O'Driscoll et al., Appl. Environ. Microbiol. 62:1693-1698, 1996). In the present study, one such mutant, ATM56, demonstrated an increased ability to survive in low-pH foods and during milk fermentation when compared with the wild-type strain. Significant numbers of ATM56 could be recovered even after 70 days in both whole-fat and low-fat cheddar cheese. Collectively, the data suggest that ATR mechanisms, whether constitutive or induced, can greatly influence the survival of L. monocytogenes in low-pH food environments.

Adaptation, Physiological↗

PubMed1996

Problem of diagnosis in postmortem brain studies of schizophrenia.

OBJECTIVE: The purpose of this study was to determine 1) the reliability of diagnoses of schizophrenia at coronal autopsy and 2) the degree to which the use of different diagnostic instruments for schizophrenia would affect postmortem brain research. METHOD: Eighty-three subjects, recorded at coronal autopsy as having had schizophrenia, were referred for neurochemistry studies. The diagnoses reported to the state coroner's office were reevaluated by a review of psychiatric case histories by clinicians using semistructured assessment and diagnostic criteria. RESULTS: The application of DSM-III-R, Research Diagnostic Criteria (RDC), ICD-10, Schneiderian, and Feighner criteria to the diagnosis of the 83 subjects revealed that 63.9%, 48.2%, 48,2%, 43.4%, and 42.2%, respectively, met the criteria for schizophrenia. Highest concordance was between the RDC and ICD-10 systems, while lowest concordance was between the RDC and Schneider systems. CONCLUSIONS: These data suggest that unless carefully reviewed, diagnosis may be a major confounding factor in postmortem studies of brain tissue from subjects with schizophrenia.

Adult↗

PubMed1996

Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration.

PURPOSE: To determine the long-term impact on disease-free survival (DFS) and overall survival (OS) of adjuvant anthracycline-based chemotherapy, when prospectively compared by random allocation with standard cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive (N+) breast cancer patients. PATIENTS AND METHODS: Two hundred forty-nine patients with N+ breast cancer, recruited from eight French cancer centers, were randomized to receive 12 monthly cycles of adjuvant chemotherapy, either CMF (n = 112) or doxorubicin, vincristine, cyclophosphamide, and fluorouracil (AVCF) (n = 136). All had a negative metastatic work-up before inclusion, which was stratified by accrual center, tumor stage (International Union Against Cancer [UICC]), and menopausal status. RESULTS: No severe adverse effect related to grade 4 (World Health Organization [WHO]) toxicity was observed. There was no difference in second primary tumor incidence between the two arms. The treatment given was 88% of planned for AVCF and 75% for CMF in both premenopausal and menopausal patients. With a median follow-up time of 16 years (range, 13 to 17), the OS and DFS rates are significantly longer in the AVCF arm (56% v 41% [P = .01] for OS, and 53% v 36% [P = .006] for DFS). These differences are significant, irrespective of tumor stage (T1 to T2 v T3 to T4), and remain positive in patients with or without postoperative locoregional radiotherapy (55% of cohort). When analyzed according to menopausal status, the differences remain significant only for premenopausal patients. CONCLUSION: This set of mature controlled data confirms the added value of anthracycline-based combination adjuvant therapy for N+ breast cancer patients when compared with CMF, with both regimens given for 1 year.

Adult↗

PubMed1996

Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study.

Glomerular hyperfiltration has been proposed as an independent risk factor for the development of diabetic nephropathy in patients with IDDM. In a case-controlled prospective study of IDDM patients without albuminuria, serial glomerular filtration rate (GFR) measurements were performed over an observation period of 10 years. A group of 25 IDDM patients (20 men, 5 women; initial age, 29 [17-49] years) with glomerular hyperfiltration (GFR >135 ml x min(-1) x 1.73 m(-2)) were matched for age, sex, and duration of diabetes with 25 IDDM patients (20 men, 5 women; initial age, 30 [17-48] years) with glomerular normofiltration (GFR 83-135 ml x min(-1) x 1.73 m(-2)). GFR, urinary albumin excretion rate (AER), blood pressure, and glycated hemoglobin were measured at baseline and at 5, 8, and 10 years. The two groups had similar entry levels of blood pressure, AER, and glycated hemoglobin. Metabolic control was similar in the two groups during follow-up. The final GFR remained higher in the group with hyperfiltration (122 [109-135] vs. 103 [95-111] ml x min(-1) x 1.73 m(-2); P = 0.02) despite a nonsignificantly faster rate of fall of GFR compared with that of the control group (2.54 [1.20-3.88] vs. 1.50 [1.01-1.99] ml x min(-1) x year(-1); P = 0.14). A similar number of patients in each group progressed to either microalbuminuria or macroalbuminuria (n = 4 vs. n = 3) or developed hypertension (blood pressure, >160/95 mmHg; n = 3 vs. n = 4). End-of-study AER was, however, higher in the group with hyperfiltration (geometric mean [95% CI]: 18.9 [11.3-31.6] vs. 11.0 [8.1-15.0]; P = 0.05), and baseline glomerular hyperfiltration was an independent determinant of end-of-study blood pressure (P = 0.04). The strongest predictors of end-of-study AER and blood pressure were their baseline values (P < 0.04 and P < 0.01, respectively). In conclusion, levels of AER and blood pressure are the main risk factors for renal outcome, while glomerular hyperfiltration appears to play a lesser role.

Adolescent↗

PubMed1996

Incidence of head injury: lasting effects among college students and working adults in the general population.

224 (21%) of 1067 persons in a nonclinical population surveyed had one or more head injuries resulting in unconsciousness. They had a total of 306 head injuries with 113 (31%) of them resulting in lasting neurological effects. Both in a pilot project and in the main study, headache was the most commonly reported of an array of symptoms that are essentially a postconcussion syndrome.

Adolescent↗

PubMed1996

[Research design for patient selection in clinical trials phase II].

Phase II trials play a key role in the development of a treatment, because they are crucial in deciding whether or not to proceed to phase III. In the event of the evaluation of a new treatment given to only one group of subjects, multi-stage designs were developed to include subjects in phase II trials. Gehan's two stage designs stop inclusion of subjects if no success is observed among the first n1 subjects. They are easy to use, but have the disadvantage of exposing many subjects to an inefficient treatment at the second stage. Fleming's multi-stage designs and Simon's two stage designs permit the early termination of a trial when the intermediate results are extreme, either in favor of the efficiency or in favor of the inefficiency of the treatment. Simon's plans minimize either the average or the maximum number of subjects exposed to ineffective treatment. Ensign's three stage designs combine the first stage of Gehan with the two stages of Simon. These plans are interesting because they can reject a treatment quickly after a long run of failures which minimizes the average number of subjects exposed to an ineffective treatment.

Bias↗