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Biomedical subjects

J Clayton

Publications and source records attributed to J Clayton.

At least 91 records · Page 5Linked to original sources

No evidence for sex ratio distortion in relation with feto-maternal HLA-DR compatibility.

Two separate studies have shown a distortion in the sex ratio of first born children from HLA-DR compatible parents (Ober et al. 1985, Radvany et al. 1987). Kilpatrick (1987) was unable to confirm this distortion on an independent family data set. The question of the HLA-DR related sex ratio distortion still remained open. In the data set, "Provinces Françaises" families from 15 French provinces and Quebec were tested for a number of genetic markers including HLA-DR. In 1304 of these families, the HLA-DR results and family structure information were sufficient to allow the testing of this hypothesis. There were 2265 male and 2156 female children (overall sex ratio: 1.05); 1307 males and 1237 females were HLA-DR typed. In this group, the sex ratios are little different from those in the overall set, except for the firstborns which exhibit an apparent increase in the sex ratio. When dividing the sample between children fully HLA-DR compatible with their mother and those incompatible (i.e. having one antigen not present in the mother), the sex ratios in the two groups are little different whatever the birth order. This analysis has failed to observe any significant distortion in the sex ratio related to fetomaternal compatibility in agreement with the study of Kilpatrick. We conclude that, if such a distortion exists, it must be small.

Female↗

Production of an ovine monoclonal antibody to testosterone by an interspecies fusion.

Hybridomas were made between NS1/1-Ag4-1 mouse myeloma cells and peripheral blood lymphocytes from a sheep immunized with a testosterone-protein conjugate. ELISAs were developed to detect ovine IgG and specific ovine anti-testosterone and these were used to screen the colonies. Although the cells fused acceptably only 3% of colonies secreted detectable quantities of antibody. The antibody was secreted at low levels (2.5 ng/ml) but was of high affinity (KD = 7.63 x 10(-12) M/1). One line, O/M 4.22, continued to secrete in culture for four months until the termination of the experiment.

Animals↗

Neuroblastoma: new approaches to diagnosis.

Monoclonal antibodies can play an important part in distinguishing neuroblastoma from other small round cell tumours of childhood. In addition, they have been useful in the identification of metastatic tumour cells in bone marrow. Though these roles for antibodies are now well proven, other functions for these reagents such as radioimmunolocalization and targeted therapy need further evaluation. The problems in the diagnostic use of monoclonal antibodies are reviewed and an assessment given on the type of panels that can be constructed as diagnostic aids. Other new diagnostic approaches in vivo and in vitro are reviewed for comparison. The rapidly developing specialties of molecular biology and molecular cytogenetics will almost certainly have an impact on the diagnosis and prognosis of patients with neuroblastoma. Although these are currently research tools, in a short time they will be in use in routine diagnosis. With the increased basic research into neuroblastoma, it is hoped that it will not be too long before the overall survival rate for the disease is improved. In the meantime the new diagnostic approaches outlined in this paper will ensure that patients are treated with an appropriate chemotherapeutic regimen and will allow the selection of subgroups of individuals for new aggressive chemo/radiotherapeutic protocols.

Antibodies, Monoclonal↗

Preparation of a bovine monoclonal antibody to testosterone by interspecies fusion.

This communication reports the first successful attempt to produce a hybridoma cell line secreting bovine immunoglobulin to a small hapten, starting with peripheral blood lymphocytes, rather than spleen or lymph node cells. A heteromyeloma line, sensitive to selective media, was made by fusing NS1/1-Ag4-1 mouse myeloma cells with bovine peripheral blood lymphocytes. This cell line was then fused with blood lymphocytes from a steer immunised with a testosterone immunogen. Cell cultures were screened using an ELISA specific for bovine antibodies to testosterone. Following repeated cloning, a cell line was established which secretes moderate levels of a specific, high affinity antibody to testosterone. This particular cell line has significant potential for veterinary application and the successful fusion demonstrates the possibilities of heteromyelomas for the development of non-murine monoclonal antibodies.

Animals↗

A multipoint linkage analysis program for X-linked disorders, with the example of Duchenne muscular dystrophy and seven DNA probes.

The analysis of linkage data with multiple markers is a complex problem, only soluble with the help of computer programs. A package of programs is presented which allows the analysis of X-linked data with reasonable speed. Published data relating Duchenne muscular dystrophy and seven X-specific DNA probes are analysed. The results presented are the maximum likelihoods of the eight possible orders and the interlocus distances of the most likely order. Also calculated are the mean and standard deviation of risk for selected cases with information derived from both single probes and pair of probes bridging the disease locus.

Chromosome Mapping↗

Comparative studies between a new human rhabdomyosarcoma cell line, JR-1 and its tumour of origin.

A new human embryonal rhabdomyosarcoma cell line, designated JR-1, is described that closely resembles the tumour from which it was derived. Comparative studies, by light and electron microscopy reveal morphological features such as myofibre formation, that are concordant with embryonal rhabdomyosarcoma. Immunohistological investigations using a panel of monoclonal antibodies indicate that the cell surface antigen profile of the JR-1 cell line is similar to other embryonal rhabdomyosarcomas. In addition the cell line expresses the cytoplasmic intermediate filament protein desmin, only found in cells of rhabdoid origin. Karyotyping JR-1 shows the cells to contain variable numbers of chromosomes (range 44-100). DNA flow cytometry indicates that cells have an DNA content which is approximately twice normal. The JR-1 cell line has a doubling time of 29 h in culture and, in common with several other human cell lines, produces xenografts in nude mice within 6 weeks of inoculation. With detailed studies on the original tumour and the JR-1 cell line, the latter should prove an excellent model system for investigating the biology of rhabdomyosarcoma.

Animals↗

Acute cigarette smoke exposure increases alveolar permeability in rabbits.

We measured lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (99mTcDTPA) as an index of alveolar epithelial permeability in rabbits exposed to cigarette smoke. Eighteen rabbits were randomly assigned to 3 equal-size groups: control, all smoke exposure (ASE), and limited smoke exposure (LSE). Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 20-min counting period between each subset of breaths to determine 99mTcDTPA biologic half-life (T1/2). Mean T1/2 minimum (i.e., the smallest T1/2 observed) was significantly lower (p less than 0.05) for ASE and LSE rabbits than by control rabbits. We observed a significant difference at 20 and 30 breath exposures between the control and ASE group mean values (% baseline) for T1/2, arterial blood pressure, and peak airway pressure. A combination of light and electron microscopy showed focal alveolar edema and hemorrhage in the ASE and LSE groups but no alveolar-capillary membrane damage. In summary, acute cigarette smoke exposure increases alveolar permeability as measured by 99mTcDTPA clearance, but there was no detectable ultrastructural alteration of the alveolar-capillary membrane.

Animals↗

SEQ: a nucleotide sequence analysis and recombination system.

SEQ is an interactive, self-documenting computer program that contains procedures for the analysis of nucleotide sequences and the manipulation of such sequences to allow the simulation and prediction of the results of recombinant DNA experiments.

Amino Acid Sequence↗

GEL, a DNA sequencing project management system.

We have developed an automated system for management of DNA sequencing projects. The system, named GEL, can handle data from both random sequences and from fragments whose relative positions are known. The system is highly interactive, self-documenting, and forgiving; it is designed for use by computer-naive molecular biologists. An editor designed specifically for sequences allows simple entry of data. Special functions allow direct checking and immediate editing of paired readings of the same gel. Merging of new random fragment sequences into the project as a whole is semi-automated. The user is shown probable overlaps if they exist, and can edit either the sequences or the consensus. Heuristic approaches to limiting the kinds of searches made in the merging process reduces the problem of combinatoric data overload as sequencing projects grow large. Complete histories of all entries, editing changes, and generation of consensus sequences are automatically prepared.

Base Sequence↗

Characteristics of the residency interview process preferred by medical student applicants.

This study elucidates the characteristics of the interview day preferred by medical students applying to family practice residencies. Interviews and informal meetings with residents were regarded as being the most helpful, followed by interviews with the director or faculty. Perceptions of other components of the interview day are also described. October was the month most students preferred, and two interviews each lasting 20 to 30 minutes were considered ideal. Group interviews were regarded negatively. The results of this survey are generalizable to other residency programs and could be helpful in planning the interview day.

Attitude of Health Personnel↗