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Biomedical subjects

C Willis

Publications and source records attributed to C Willis.

At least 37 records · Page 2Linked to original sources
PubMed2001

A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11).

We report mutations in a gene (PRPF31) homologous to Saccharomyces cerevisiae pre-mRNA splicing gene PRP31 in families with autosomal dominant retinitis pigmentosa linked to chromosome 19q13.4 (RP11; MIM 600138). A positional cloning approach supported by bioinformatics identified PRPF31 comprising 14 exons and encoding a protein of 499 amino acids. The level of sequence identity to the yeast PRP31 gene indicates that PRPF31 is also likely to be involved in pre-mRNA splicing. Mutations that include missense substitutions, deletions, and insertions have been identified in four RP11-linked families and three sporadic RP cases. The identification of mutations in a pre-mRNA splicing gene implicates defects in the splicing process as a novel mechanism of photoreceptor degeneration.

Alleles↗
PubMed2001

PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans.

PAX6 is widely expressed in the central nervous system. Heterozygous PAX6 mutations in human aniridia cause defects that would seem to be confined to the eye. Magnetic resonance imaging (MRI) and smell testing reveal the absence or hypoplasia of the anterior commissure and reduced olfaction in a large proportion of aniridia cases, which shows that PAX6 haploinsuffiency causes more widespread human neuro developmental anomalies.

Adult↗
PubMed2000

Quantification of free mycophenolic acid by high-performance liquid chromatography-atmospheric pressure chemical ionisation tandem mass spectrometry.

To facilitate the investigation of free mycophenolic acid concentrations we developed a high-performance liquid chromatography tandem mass spectrometry method using indomethacin as an internal standard. Free drug was isolated from plasma samples (500 microl) using ultrafiltration. The analytes were extracted from the ultrafiltrate (200 microl) using C18 solid-phase extraction. Detection was by selected reactant monitoring of mycophenolic acid (m/z 318.9-->190.9) and the internal standard (m/z 356.0-->297.1) with an atmospheric pressure chemical ionisation interface. The total chromatographic analysis time was 12 min. The method was found to be linear over the range investigated, 2.5-200 microg/l (r>0.990, n=6). The relative recovery of the method for the control samples studied (7.5, 40.0 and 150 microg/l) ranged from 95 to 104%. The imprecision of the method, expressed in terms of intra- and inter-day coefficients of variation, was <8 and <9%, respectively. Further, analysis of pooled patient plasma produced an intra-day imprecision of 6.6%. The signal-to-noise ratio at the limit of quantification (2.5 microg/l) was approximately 5:1. The mean absolute recovery (n=6) of mycophenolic acid and the internal standard were 76.0+/-13.5% and 86.0+/-9.1%, respectively. The method reported provides an accurate and precise quantification of free mycophenolic acid over a wide analytical range and thus can be used for routine monitoring and pharmacokinetic studies.

Atmospheric Pressure↗
PubMed2000

Beta-adrenoceptor signaling and its control of cell replication in MDA-MB-231 human breast cancer cells.

MDA-MB-231 human breast cancer cells express high beta-adrenoceptor levels, predominantly the beta2 subtype. Receptor stimulation by isoproterenol evoked immediate reductions in DNA synthesis which were blocked completely by propranolol and were of the same magnitude as effects elicited by high concentrations of 8-Br-cAMP. Isoproterenol-induced inhibition of DNA synthesis was maintained throughout several days of exposure, resulting in a decrement in total cell number, and the effects were augmented by cotreatment with dexamethasone; an even greater effect was seen when cAMP breakdown was inhibited by theophylline, with or without addition of isoproterenol. Despite the persistent effect of isoproterenol, receptor downregulation was evident with as little as 1 h of treatment, and over 90% of the receptors were lost within 24 h. Receptor downregulation was paralleled by homologous desensitization of the adenylyl cyclase response to beta-adrenoceptor stimulation. Dexamethasone augmented the effects of isoproterenol on DNA synthesis but did not prevent receptor downregulation or desensitization. These results indicate that beta-adrenoceptors are effectively linked, through cAMP, to the termination of cell replication in MDA-MB-231 human breast cancer cells, and that activation of only a small number of receptors is sufficient for a maximal effect. Novel pharmacologic strategies that focus on cell surface receptors operating through adenylyl cyclase may offer opportunities to combat cancers that are unresponsive to hormonal agents, or that have developed multidrug resistance.

Adenylyl Cyclases↗
PubMed2000

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL.

BACKGROUND: Standard therapy for lymphoma consists of a cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP) combination regimen. Liposomal daunorubicin (DaunoXome) is an alternative to doxorubicin for patients with lymphoma because of its more favorable safety profile and potentially more selective uptake in lymphoma. The objectives of this study were to determine the maximum tolerated dose (MTD) of liposomal daunorubucin with CVP (COP-X) and the tolerability of the regimen in patients with indolent lymphoma. PATIENTS AND METHODS: Patients with low-grade and intermediate-grade lymphoma having adequate cardiac, hepatic, and renal function were enrolled. Patients received C 750 mg/m2, V 1.4 mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50-100 mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1-5. MTD was the liposomal daunorubicin dose associated with 20% dose-limiting toxicity (ANC < 500/mm3 for > 5 days or febrile neutropenia). RESULTS: Twenty patients, median age 59 years, were treated. The liposomal daunorubicin MTD combined with CVP was 70-80 mg/m2, depending on patient population. No significant non-hematologic toxicity occurred. Response rate was 44% (2 complete and 5 partial responses). CONCLUSIONS: A liposomal daunorubicin dose of 80 mg/m2 in the COP-X regimen was well tolerated with little nonhematologic toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients.

Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the investigation of pharmacokinetic-pharmacodynamic relationships of mycophenolic acid in the clinical setting, limited blood sampling strategies have been proposed, and models from these developed, for the estimation of mycophenolic acid area under the concentration-time curve (AUC). In the current study, the authors investigated the predictive performance of six published models to estimate AUC. A total of 49 profiles from 25 renal transplant patients were used to test each model's performance against a full 14 time-point AUC. A wide range of agreement was found when predicted AUCs were compared with full AUCs using linear regression analysis (range: r2 = 0.499 to 0.836). Model 1, which uses 4 time-points over 6 hours, was found to be superior to all other models. The range of time-points used in this model takes into account patients with variable absorption. This model should be further tested on data sets from other centers. The relatively poor performance of the other models may be caused by their inability to describe the peak concentration in these patients. Caution is warranted when using limited sampling strategies on patients whose absorption of mycophenolic acid is altered, compared with those of the pharmacokinetic profiles from which the model was developed.

Adult↗
PubMed2000

Preference of female rats for the odours of non-parasitised males: the smell of good genes?

Many animals obtain reliable information about potential mates, including whether they are parasitised or not, mostly from olfactory cues in urine. Previous experiments with rodents have shown that females can detect parasites in males that are potentially transmissible during copulation, so that females can directly avoid infection by discriminating against parasitised males. Here, using choice tests, we examine whether female rats can distinguish males infected with the tapeworm Hymenolepis diminuta Rudolphi, 1819, a parasite with a complex life cycle and thus not directly transmissible among rats. Female rats tended to spend more time investigating the urine of non-parasitised males than that of parasitised males. The magnitude of the parasite burden in the infected males had no effect on the females' preference for the non-parasitised males. We also found that parasitised males had lover testosterone levels in their blood than non-parasitised males. These results suggest that females use cues in male urine reflecting either the presence of the parasite and/or lower testosterone levels to avoid parasitised males and possibly secure resistance genes for their offspring.

Animals↗
PubMed1999

Detection of antibacterial agents in warm water prawns.

Samples of cooked and raw prawns intended for human consumption were collected by officers at Southampton Port Health Authority, and tested for the presence of antimicrobial agents. Antimicrobial activity was detected in 23 out of 98 cooked prawn samples but in none of the 20 raw samples collected. Samples that showed antimicrobial activity were analysed using high performance liquid chromatography and immunoassay, resulting in the presumptive identification of trimethoprim in 15 samples, and low levels of gentamicin in three samples. Prawns in which trimethoprim was putatively detected contained bacteria with significantly greater resistance to this antibiotic than samples in which no trimethoprim was found. This suggests that the presence of antibiotics in prawn samples may be correlated with increased resistance to these drugs in the associated microflora. There are currently no guidelines regarding acceptable levels of antibiotics in seafood products. These results indicate that the use of these drugs by prawn farmers may be widespread, and may be an issue that requires further attention in the future.

Animals↗
PubMed1998

Clinical morphology of sodium lauryl sulfate (SLS) and nonanoic acid (NAA) irritant patch test reactions at 48 h and 96 h in 152 subjects.

In this study of 152 women, comparison of patch test responses between 2 irritants over 96 h at 2 symmetrical anatomical sites is studied. 2 irritants, each at 4 different concentrations (nonanoic acid (NAA) 80%, 40%, 20%, 10%; sodium lauryl sulfate (SLS) 3%, 2%, 1% and 0.5%) and using propan-1ol and 'water for injection' as the respective controls, were placed as 15 microl aliquots, soaked onto filter paper discs in Finn Chambers, on the volunteer's left and right lower back. The patches were removed at 47, and read at 48 and 96 h. Irritant reactions were evaluated for erythema and surface changes by degree and area affected. Statistical analysis of the results showed that erythema decreased with time for all concentrations of NAA, and at higher concentrations for SLS. Surface changes increased with time for SLS and at higher concentrations of NAA. There was no statistically significant difference comparing left and right sides. Traditionally in patch testing, reactions which fade after 48 h have been regarded as irritant rather than allergic. This study refutes that assumption. Data from our left to right comparisons, made in the same individuals at the same time, show that irritant reactions may be more reproducible than previously appreciated.

Adolescent↗
PubMed1997

Guidelines on sodium lauryl sulfate (SLS) exposure tests. A report from the Standardization Group of the European Society of Contact Dermatitis.

This report reviews the clinical and histopathological reactions caused by sodium lauryl sulfate (SLS), and the non-invasive methods that can characterize these reactions. Furthermore, SLS exposure techniques and factors that may influence the outcome of these exposures are discussed. Finally, guidelines are introduced for each exposure technique in order to have a uniform approach to SLS testing in man. Since different study aims warrant different testing conditions, we have proposed 2 categories, namely susceptibility testing and provocative testing, tailored to the aim with which the study is performed.

Dermatitis, Contact↗
PubMed1994

What is the significance of black-white differences in risky sexual behavior?

A sample of African-American and white young adults were classified as having multiple sex partners or one sexual partner. Subjects with multiple sexual partners were more likely to use drugs and practice risky sexual behaviors such as having anal intercourse, having sexual experiences with a prostitute, and having a history of gonorrhea (P < .001) and genital warts (P < .01). Additional analyses were conducted to determine African-American versus white differences in risky sexual behaviors. Results indicated that whites in the multiple partners and single partner groups were more likely to engage in anal and oral sex, while African Americans were more likely to have sex with prostitutes. Attitudes about the use of condoms differed significantly by multiple partner status (P < .004) and gender (P < .007), but not ethnicity. However, angry reactions about the use of condoms occurred more with African Americans (P < .003) and males (P < .05) than with whites or females. While whites reported a greater use of drugs and a significantly higher level of knowledge about HIV/AIDS, African Americans reported a significantly greater perception of risk for being exposed to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (P < .01) and significantly more gonorrhea (P < .10), syphilis (P < .05), and HIV/AIDS (P < .05). No whites in our sample were treated for syphilis nor had they tested positive for HIV/AIDS. On the other hand, 4.5% of the total sample of African Americans reported testing positive for HIV/AIDS. Finally, the results from discriminant analysis indicate that a large number of variables significantly discriminate between subjects who engage in risky sexual behaviors and those who do not. Although there is some similarity in the variables for African Americans and whites, there was tremendous variability between the ethnic groups in the factors that predict risky behaviors. These findings are discussed with reference to the need to develop HIV/AIDS prevention programs for African Americans that are based on data derived from African-American populations rather than from black versus white comparison studies.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cascade testing for carrier status in cystic fibrosis in a large family.

The offer to determine carrier status for cystic fibrosis (CF) was made to the 230 descendants of a couple who were presumed to carry the delta F508 mutation. "Cascade testing" was employed, in which the mutation is followed from the oldest generation down. Compliance was over 75% and family members were relieved of the anxiety engendered by uncertainty. In one couple considering having a family, both partners were found to be carriers.

Adolescent↗
PubMed1992

Delayed allograft rejection in mice transgenic for a soluble form of the IL-4 receptor.

Accumulating evidence suggests that in serum and other biological fluids, cytokine binding is a property associated with soluble proteins, including a high-affinity soluble version of the IL-4 receptor (sIL-4R). While it is tempting to speculate that sIL-4R might act as a serum carrier protein or serve to inhibit or modulate IL-4 action, specific biological roles for sIL-4R remain to be established. To further assess the immunoregulatory and therapeutic potential of sIL-4R and other soluble receptors, we have created transgenic mice which constitutively express elevated levels of biologically active sIL-4R. Phenotypic characterization of lymphoid organs in sIL-4R transgenic mice revealed normal numbers of B and T cells and normal surface marker expression. Splenic lymphocytes displayed normal in vitro activities as measured by the PFC response and generation of cytotoxic T cells. In addition, antigen-specific IgE and IgG1 in vivo responses were similar in control and transgenic mice. Despite the apparent developmental normality of the sIL-4R transgenic mice, these animals were markedly deficient in the ability to reject cardiac allografts, suggesting that IL-4 is critical for the generation of alloreactivity. The results further suggest that the ability of sIL-4R to regulate IL-4 activities may be under the control of complex interactions that remain to be elucidated.

Amino Acid Sequence↗
PubMed1992

Do African-American men and women differ in their knowledge about AIDS, attitudes about condoms, and sexual behaviors?

This study identified a sample of young African-American men and women classified as having multiple sex partners or one sex partner. Of the 149 men, 71 (47%) were classified as having multiple sex partners and 78 (53%) as having one sex partner. Of the 165 women, 29 (19%) were classified as having multiple sex partners and 126 (81%) as having one sex partner. Results indicated that the groups did not differ in their knowledge about acquired immunodeficiency syndrome (AIDS). However, attitudes about condom use differed significantly by gender (P less than .01) and by multiple sex status (P less than .001). Angry reactions regarding the negotiation of condom use occurred more with men than with women (P less than .05). Men and members of the multiple sex partners group tended to engage in more risky sexual behavior. These two groups also had a significantly (P less than .001) higher incidence of gonorrhea. While the multiple sex partners group had significantly more smokers (P less than .01), drinkers (P less than .01), and crack users (P less than .05), men were significantly higher consumers of marijuana (P less than .001) and alcohol (P less than .01). Overall, the results indicate that African Americans are knowledgeable about AIDS, but there appears to be a gap between knowledge and risky sexual behaviors. Prospective studies are needed to clarify the factors that determine the relationship (or lack of) between knowledge and risky sexual behaviors. Without such studies, a major part of the foundation that is needed for the development of sensitive and effective AIDS prevention programs for African Americans will be missing.

Acquired Immunodeficiency Syndrome↗
PubMed1991

An evaluation of AIDS education: a quasi-experimental exploration.

This study reports on a quasi-experimental study designed to evaluate the relationship between receiving classroom instruction and subsequent AIDS knowledge, behavior, and attitudes. Survey information was gathered from 61 students enrolled in an AIDS course and 68 students enrolled in "control" courses. Both groups were pretested at the beginning of the semester and again at the end of the semester concerning AIDS knowledge, behavior, and attitudes. The results obtained indicated that there was a widespread acceptance of the conventional wisdom concerning AIDS in both the experimental and control groups prior to the study. Few behavior changes were observed as a result of the AIDS curriculum. Three empirically distinct factors, "interaction," "constraint," and "testing," emerged from the attitude measures. Respondents were more accepting of interacting with persons with AIDS across time. Moreover, respondents in the experimental group were more reticent to advocate mandatory AIDS testing vis-à-vis those in the control group across time.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Chronic massive fetomaternal hemorrhage: a case report.

We report a case of massive chronic fetomaternal hemorrhage with remarkable fetal compensation. The labor course was complicated by a fetal heart rate pattern showing decreased long- and short-term variability and the eventual development of persistent late decelerations. The fetal scalp blood pH and cord blood pH values were normal. A living male infant was delivered by cesarean section for persistent late decelerations. A Kleihauer-Betke stain on a maternal blood sample was positive at 14.5%, which is equivalent to 700 mL of fetal blood in the maternal circulation.

Adult↗