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M Paterson

Publications and source records attributed to M Paterson.

At least 19 recordsLinked to original sources

The extragenomic action of progesterone on human spermatozoa is influenced by redox regulated changes in tyrosine phosphorylation during capacitation.

Capacitation had no effect on the ability of progesterone to elicit a rapid calcium transient in the acrosomal domain of human spermatozoa but had a marked influence of the ability of this steroid to induce a biological response. The development of this responsiveness to progesterone appeared to be redox regulated in that it was promoted by the stimulation of reactive oxygen species generation and inhibited by the presence of antioxidants, including catalase and membrane permeant thiols. The ability of redox conditions to influence the biological responsiveness of human spermatozoa did not involve changes in the dynamics of the calcium transients induced by progesterone but was causally linked with clear differences in tyrosine phosphorylation. We conclude that the ability of human spermatozoa to respond to the calcium transients induced by progesterone depends on a background of phosphotyrosine expression that can be profoundly influenced by the redox status of the spermatozoa during capacitation.

Humans

Sequence databases and homology searching using the World Wide Web.

RNA, DNA and protein sequence data produced in laboratories around the world may be freely accessed by other scientists using the Internet. Originally, these sequence databases were compiled from published literature, but now researchers may deposit sequence data directly, using the World Wide Web. Almost 50,000 protein sequences and over 600,000 nucleotide sequences are available, forming a significant scientific resource. By comparing novel sequence data with sequence entries and structural data showing significant homology, it is possible to predict the function and three-dimensional structure of novel proteins.

Amino Acid Sequence

The potential of the zona pellucida as a target for immunocontraception.

PROBLEM: To investigate the contraceptive potential of the zona pellucida. METHOD: Generation of antibodies against native and recombinant zona glycoproteins which have then been assessed for their capacity to disrupt sperm-zona interaction in vivo and in vitro. The animal model selected for these studies was the common marmoset and the end points examined were antibody titre, ovarian cyclicity and fertility. RESULTS: The fact that antibodies against the major zona glycoprotein, ZP3, block both the primary and secondary phases of sperm-zona interaction suggests that this molecule might have potential for contraceptive vaccine development. Active immunization of marmoset monkeys with native porcine ZP3 or recombinant human ZP3 produced long term infertility but also precipitated a premature decline in the primordial follicle population. CONCLUSIONS: Future studies will have to determine whether a safe, effective vaccine can be engineered by coupling unique B-cell epitopes from ZP3 to foreign T-cell antigens.

Animals

Parent comprehension of polio vaccine information pamphlets.

BACKGROUND: Medical information pamphlets often are written using language that requires a reading level higher than parents of many pediatric patients have achieved. Anecdotal reports suggest that many parents may not readily understand the federally mandated Public Health Service vaccine information pamphlets prepared by the Centers for Disease Control and Prevention (CDC) in 1991. The level at which the pamphlets need to be written for low-reading-level parents is undetermined, as is whether parents reading at higher levels will accept low-reading-level materials. METHODS: To determine whether a simple pamphlet prepared at a low reading level using qualitative and adult education techniques would be preferable to the available CDC polio vaccine information pamphlet, we conducted an integrated qualitative-quantitative study. We compared the parent reading time and comprehension of a simplified pamphlet (Louisiana State University, LSU) comprising 4 pages, 322 words, 7 instructional graphics, and a text requiring a 6th grade reading ability with the equivalent 1991 CDC vaccine information pamphlet comprising 16 pages, 18,177 words, no graphics, and a text requiring a 10th grade reading level. We measured the reading ability of 522 parents of pediatric patients from northwest Louisiana seen at public clinics (81%) and in a private office (19%). Of the entire group, 39% were white, 60% African-American, and 1% Hispanic; the mean age was 29 years; the mean highest grade completed was 12th grade 3 months; and the reading level was less than 9th grade in 47% of parents and less than 7th grade in 20%. After parents were given one of the pamphlets to read, their reading time, comprehension, and attitude toward the pamphlet were measured. RESULTS: Mean comprehension was 15% lower for CDC than for LSU (56% vs 72% correct; P < .001) and reading time was three times longer for CDC than for LSU (13 minutes 47 seconds vs 4 minutes 20 seconds; P < .0001). These trends were significant for parents reading at all but the lowest levels. Mean comprehension and reading time did not differ among parents reading at the third grade level or less. However, mean comprehension was greater and reading time lower for LSU among parents at all reading abilities greater than the third grade. Parents in the private practice setting took the longest time to read the CDC (20 minutes 59 seconds vs 5 minutes 46 seconds, LSU), yet their comprehension on the LSU was significantly higher than on the CDC (94% vs 71%; P < .0001). Two focus groups of high-income parents were unanimous in preferring the LSU. CONCLUSIONS: A short, simply written pamphlet with instructional graphics was preferred by high- and low-income parents seen in private and public clinics. The sixth grade reading level appears to be too high for many parents in public clinics; new materials aimed at third to fourth grade levels may be required. The new 1994 CDC immunization materials, written at the eighth grade level, may still be inappropriately high. The American medical community should adopt available techniques for the development of more effective patient-parent education materials.

Adolescent

Evaluation of zona pellucida antigens as potential candidates for immunocontraception.

Antibodies directed against the zona pellucida can interrupt sperm-egg recognition in vitro. However, the mechanisms by which anti-zona antibodies exert this contraceptive effect in vivo remain uncertain. There is an accumulating body of evidence to suggest that active immunity against zona antigens not only induces infertility via an antibody-mediated interruption of sperm--egg interaction but also disrupts normal ovarian function. We have evaluated the consequence of inducing active immunity against purified recombinant human ZP3 (rec.hZP3) and human ZP3 peptides, using the marmoset monkey, Callithrix jacchus, as an animal model. Although infertility was established in animals that received rec.hZP3, it was associated with ovarian dysfunction characterized by suppression of folliculogenesis and depletion of the primordial follicle pool. Immunization with continuous human ZP3 peptides, identified by epitope mapping studies, did not induce ovarian pathology but the antibody titres were insufficient to suppress fertility significantly and consistently. Clearly, further research is required to identify and segregate epitopes on the zona glycoproteins that are capable of inducing infertility without any side effects.

Animals

Hen's teeth and whale's feet: generalized characters and their compatibility.

We propose a new model of computation for deriving phylogenetic trees based upon a generalization of qualitative characters. The model we propose is based upon recent experimental research in molecular biology. We show that the general case of determining perfect compatibility of generalized ordered characters is an NP-complete problem, but can be solved in polynomial time for a special case.

Algorithms

Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function.

The redox status of human spermatozoa was found to have a profound influence on the fertilizing potential of these cells in association with qualitative and quantitative changes in the patterns of tyrosine phosphorylation. In general, oxidizing conditions enhanced tyrosine phosphorylation and stimulated sperm function, whereas reducing conditions had the opposite effect. Unstimulated human spermatozoa exhibited low levels of spontaneous acrosomal exocytosis and sperm-oocyte fusion and minimal reactive oxygen species generation, while phosphotyrosine expression was largely confined to a single protein of 116 kDa. However, if the spermatozoa were exposed to oxidizing conditions through the addition of exogenous H2O2, or the stimulation of endogenous NADPH-dependent reactive oxygen species generation, then a dramatic increase in tyrosine phosphorylation was observed (major phosphotyrosyl bands at 222 kDa, 200 kDa, 159 kDa, 133 kDa, 116 kDa and 82 kDa) in concert with the functional activation of the spermatozoa. A causal association between reactive oxygen species generation, tyrosine phosphorylation and sperm function was indicated by studies with the ionophore, A23187, which induced high rates of spermoocyte fusion together with enhanced rates of reactive oxygen species production and the increased expression of phosphotyrosyl proteins. This functional response to A23187 could be abrogated, without any concomitant change in sperm motility or viability, by using membrane permeant thiols or catalase to suppress the reactive oxygen species-induced increase in phosphotyrosine expression. The fact that the biological responses of human spermatozoa to biological agonists (recombinant human ZP3 and progesterone) could also be inhibited by catalase indicated the general relevance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome

Contraceptive vaccines.

Three major approaches to contraceptive vaccine development are being pursued at the present time. The most advanced approach, which has already reached the stage of phase 2 clinical trials, involves the induction of immunity against human chorionic gonadotrophin (hCG). Vaccines are being engineered based on conjugates incorporating tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centred on the beta-subunit of this molecule. Clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. However, the long term consequences of such immunity in terms of safety or efficacy are, as yet, unknown. The alternative approaches to contraceptive vaccine development involve the induction of immunity against gamete-specific antigens found on the surface of the human spermatozoon or the zona pellucida. There is an abundance of experimental and clinical data to suggest that this approach is feasible although the biochemical characterization and synthesis of candidate antigens is still incomplete.

Animals

Faculty research productivity in allied health settings: a TQM approach.

Faculty research productivity in colleges of allied health has often been discussed in the literature over the last five years. Articles have focused on the problem of faculty research productivity from various viewpoints, but none have used a theoretical framework to analyze the problem. The total quality management (TQM) framework is currently being used in health care to improve quality and productivity. This article uses the TQM framework to synthesize literature concerning faculty research productivity and verifies the current relevance of synthesis findings using an allied health faculty survey. These analyses show that the TQM framework is useful in suggesting ways to increase faculty research productivity in colleges of allied health.

Allied Health Personnel

Analysis of the contraceptive potential of antibodies against native and deglycosylated porcine ZP3 in vivo and in vitro.

We have undertaken a comparative analysis of the contraceptive activity of antibodies directed against the porcine sperm receptor zona pellucida antigen (ZP3) and its Mr = 32,000 polypeptide core (DGZP-32). The strategies employed for this analysis included the induction of active immunity in a primate, the common marmoset, and an in vitro fertilization protocol involving the use of viable human ova. In both experimental situations, antibodies against ZP3 were shown to exhibit contraceptive activity, leading respectively to the induction of long-term infertility in the primate model and to the complete inhibition of human fertilization in vitro. The in vivo studies also revealed that the induction of high titer antibodies against ZP3 was inevitably associated with the appearance of an ovarian pathology characterized by the progressive depletion of the primordial follicle pool within one to two years. This side effect could not be alleviated by the use of DGZP-32 as antigen since the induction of immunity against this polypeptide was also associated with the eventual appearance of an ovarian pathology identical to that observed with ZP3. Furthermore, the DGZP-32 peptide was less effective than ZP3 in inducing the formation of antibodies capable of inhibiting the fertilization of human ova in vitro. We conclude that significant problems remain with the use of deglycosylated zona peptides for the development of contraceptive vaccines and that their potential will not be realized until the epitopes responsible for the induction of infertility and the primordial follicle depletion have been identified and segregated.

Animals

Phase II studies of ifosfamide alone and in combination in cancer of the cervix.

A series of phase II studies using ifosfamide (IFX) as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer have been coordinated at the West Midlands CRC Clinical Trials Unit (Birmingham, UK). The aims of these studies were to identify single agents and combination regimens that may be of value for palliation and have potential for use as neoadjuvant and adjuvant therapy at the time of primary treatment. A total of 79 patients with disease non-amenable to radical local therapy were treated with single-agent IFX or the BIP combination. In 30 patients treated with single-agent IFX, 10 objective responses (30%) were seen, with 1 complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxicity included alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function and disturbance of consciousness. These data indicate that IFX is highly active in cervix cancer and, in combination with bleomycin and cisplatin, can be used for effective palliation and cytoreduction in greater than 70% of patients. IFX-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomised trials.

Adult

Factors associated with childhood cancer in a national cohort study.

Information on 16,193 infants delivered in Great Britain in one week of April, 1970 was collected by midwives at the birth and during the first 7 days of life. Using multiple sources, 33 children developing cancer by 1980 were identified from this cohort, giving an incidence of 2.04 per 1,000 total births by the age of 10. Comparisons of these 33 children were made with 99 controls, three for each index case, matched on maternal age, parity and social class. Statistically significant associations were initially found with maternal X-rays and smoking during pregnancy, and the use of analgesics such as pethidine during labour, confirming the findings of retrospective case-control studies. Unexpected statistically significant associations were found with delivery of the child outside term, and drug administration in the first week of life. The latter was found in the absence of an association with neonatal abnormalities in the child and relates mostly to the administration of prophylactic drugs such as vitamin K. Logistic regression involving the whole cohort showed independent statistical associations with maternal smoking (OR 2.5), and drugs to the infant (OR 2.6). After adjusting for these factors no other statistically significant associations were found.

Adult

Gradient high-performance liquid chromatography using alkylphenone retention indices of insecticidal extracts of Penicillium strains.

Purified extracts of four Penicillium strains which were active against the insect pest Spodoptera littoralis were analysed by gradient high-performance liquid chromatography (HPLC) for secondary metabolites using alkylphenone retention indices. HPLC of pure secondary metabolite standards detected previously in the extracts by thin-layer chromatography (TLC) was undertaken in order to obtain bracketed retention indices. More metabolites were detected by HPLC than by TLC, although some compounds detected by TLC in some strains were not detected by this HPLC method. A minority of metabolites were exclusive to each strain, and most were produced by more than one strain. The profiles were more characteristic of each strain when only the larger peaks were considered. This emphasizes the importance of detection limits in secondary metabolite analysis. Some of the implications of these analyses to fungus toxicity and systematic mycology are discussed.

Chromatography, High Pressure Liquid

Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer.

We report a phase II study of bleomycin, ifosfamide, and cisplatin (BIP) in cervical cancer. Our aims were to assess response rate, toxicity, and survival in women treated with this combination. Among 49 patients, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxic effects were assessed in 186 treatment cycles. All patients had alopecia and nausea and vomiting. Other effects included myelosuppression, infection, reduction in renal function, and disturbance of consciousness. These data indicate that BIP is highly active against advanced and recurrent cervical cancer.

Adult

The role of ifosfamide in cervical cancer.

A series of phase II studies using ifosfamide as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer were coordinated at the West Midlands Cancer Research Campaign Clinical Trials Unit, Birmingham, UK. The aim of these studies was to identify single agents and combination regimens that might be of value for palliation and have potential for neoadjuvant and adjuvant therapy in primary treatment. Ninety-eight patients were studied. Seventy-nine patients with disease not amenable to radical local therapy were treated with single-agent ifosfamide or the BIP combination. In 30 patients treated with single-agent ifosfamide, ten objective responses (33%) were seen, with one complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with ten complete responses (20%). Eleven (79%) of 14 patients with primary inoperable disease had at least a 50% reduction in tumor bulk before radical local radiotherapy. Toxicity resulted in alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function, and disturbance of consciousness. There was no evidence that neoadjuvant chemotherapy enhanced the acute toxic effects of pelvic radiotherapy. These data indicate that ifosfamide is highly active in cervical cancer and that in combination with bleomycin and cisplatin, it can be used for effective palliation and cytoreduction in around 70% of patients. Ifosfamide-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomized trials.

Adult

The cost effectiveness of auranofin: results of a randomized clinical trial.

In a 6-month randomized trial at 14 sites, the cost effectiveness of auranofin (AF) treatment for patients with rheumatoid arthritis was gauged in comparison with placebo. Measures of global health and of impacts on daily life suggest that the benefits of disease modification outweigh adverse effects after 4 and 6 months of treatment (p less than 0.01), with negligible differences between placebo and treated patients after 1 and 2 months. Additional medical costs directly associated with AF treatment amounted to $778/patient annually. Observed differences in less direct medical costs, help received, and earnings were not statistically significant.

Adult