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Biomedical subjects

K Fowler

Publications and source records attributed to K Fowler.

8 recordsLinked to original sources
PubMed1992

On the use of tester stocks to predict the competitive ability of genotypes.

It has been recently claimed that the outcome of competition between two phenotypically indistinguishable strains cannot be predicted from comparisons of their respective performances against a mutant tester stock. Our aim in the present paper is to disprove this claim and to show the potential pitfalls of deriving conclusions from a statistical analysis of experimental designs commonly employed for the study of competitive interactions in genetically homogeneous and heterogeneous mixtures. Using our own data, we conclude that evaluating the competitive interactions of phenotypically indistinguishable wild-type strains by competing them against mutant marked stocks still remains a valuable method.

Analysis of Variance↗
PubMed1992

Patient-interactive, computer-controlled neurological stimulation system: clinical efficacy in spinal cord stimulator adjustment.

Over the past 20 years, continuing technical advances have rendered spinal cord stimulation an easily implemented low-morbidity technique for the management of chronic intractable pain in properly selected patients. Percutaneous methods for the insertion of arrays of multiple epidural electrodes, which are driven by noninvasively programmable "multichannel" implanted devices, have been among the most important of these technical improvements. The same implanted electronics may be used with peripheral nerve or intracerebral electrodes. If the capabilities of this new hardware are to be used to full advantage, a major investment of time and effort is required to adjust the system postoperatively for optimum effect. Ideally, these adjustments should be based upon psychophysical data, obtained in a manner that minimizes influences such as potential operator bias or stimulus presentation-order effects. These requirements have been met by the development of a computerized system designed for direct patient interaction and for greater ease of operation than the standard external devices used with these implants. The system has been tested clinically in 25 patients with spinal cord stimulation for pain. It rapidly tests the available electrode combinations and stimulus pulse parameters at a rate comparable to or greater than that of a skilled human operator using the standard device. It records detailed graphic data and patient analog ratings at varying thresholds and implements "pain drawing" methods with novel input and analytical techniques. This patient-interactive computerized system has proved to be safe and effective clinically. The time required by the average patient working with this system to adjust the stimulator is comparable to or less than the time required by the same patient working with a physician's assistant. Psychophysical data collected by the system may be correlated with clinical observations. Ongoing development will permit delivery of novel pulse sequences and protocols to assess the mechanisms by which stimulation affords relief from pain.

Electric Stimulation Therapy↗
PubMed1990

Unusual X chromosome inactivation in a mentally retarded girl with an interstitial deletion Xq27: implications for the fragile X syndrome.

A de novo interstitial deletion (X)(q27.1q27.3), between the loci DXS 105 and F8, has been found in a mentally retarded female. The deleted X chromosome is preferentially early replicating in fibroblasts, B cells and T cells, suggesting that the missing region plays a role in inactivation of the X chromosome. None of the available DNA probes except DXS 98 maps to the deleted region of about 10,000 kb. The locus FRAXA is either included in the deletion, or located close to the distal break point.

Blotting, Southern↗
PubMed1988

Analysis of degradation of the basement membrane protein nidogen, using a specific monoclonal antibody.

A monoclonal antibody was produced against purified nidogen extracted from a mouse basement-membrane-producing tumor. This antibody reacted with a determinant on Nd-40, a rod which separates the globular domains of nidogen. Antigenicity depends on intrachain disulfide bonds within this rod. The monoclonal antibody was used to detect nidogen fragments after proteolytic cleavage of isolated nidogen, and nidogen complexed to laminin. The data indicate that thrombin and thermolysin generated very different patterns of degradation, but in both cases no differences were found between isolated and complexed nidogen. In contrast, nidogen in the laminin-nidogen complex was much less degraded by trypsin than isolated nidogen, indicating that an interaction between these basement membrane components reduces the susceptibility of nidogen to trypsin digestion. Immunofluorescent studies, using the monoclonal antibody on sections of the EHS tumor after proteolytic digestion, showed that the retention or disappearance of the Nd-40 determinant correlated with the in vitro digestion pattern of the laminin-nidogen complex.

Animals↗
PubMed1988

A human complement-fixing monoclonal anti-human lymphocyte antibody of rat origin.

MARCH 1E11 is an IgM monoclonal anti-human lymphocyte antibody of rat origin with the capacity to utilise both human and rabbit complement. The antibody reacts with all thymocytes and with all peripheral blood T and B lymphocytes. The treatment of human bone marrow or human peripheral blood mononuclear cells (PBMC) with MARCH 1E11 and either pooled human serum or autologous serum as a complement source resulted in cytolysis of greater than 99% of OKT3-positive lymphocytes. Under these conditions, progenitor cell recovery (colony-forming unit (CFU-c), burst forming unit--erythroid (BFU-e) and colony-forming unit--mixed (CFU-mix)) was greater than 90% of that of untreated cells. The response of treated marrow or PBMC to phytohaemagglutinin stimulation and in mixed leucocyte reactions demonstrated a reduction in thymidine incorporation to values similar to those obtained for unstimulated cells. The antibody does not cause modulation of the cell surface antigen and does not react significantly with non-lymphoid tissues. This monoclonal antibody may be useful for in vitro elimination of T lymphocytes from allogeneic bone marrow used for transplantation. The antibody may also be useful for treatment protocols requiring lymphoid depletion or immunosuppression as in organ transplantation.

Animals↗
PubMed1987

Computer-controlled, patient-interactive, multichannel, implanted neurological stimulators.

Programmable implantable neurological stimulation systems with multiple electrodes have many advantages in clinical use, but time-consuming postoperative adjustment of stimulation parameters is a distinct disadvantage. A personal computer interface to standard commercial radiofrequency-coupled devices has been developed, permitting direct patient interaction to expedite this process. In addition, the system permits simulated multichannel operation and implementation of various modulation schemes.

Electric Stimulation Therapy↗
PubMed1986

Vectors for expression and amplification of cDNA in mammalian cells: expression of rat phenylalanine hydroxylase.

We have constructed two recombinant plasmid vectors for direct expression and amplification of cDNA in mammalian cells. Each vector carries two dominant selectable markers (the bacterial neo gene and the mouse DHFR gene), a promoter sequence (viral LTR in pAV009/A+, and sheep metallothionein promoter in pMT010/A+), a polyadenylation signal sequence, and a Bam HI site to allow insertion of cDNA. We have used these vectors to prepare recombinant clones for the expression of rat phenylalanine hydroxylase (PH) in LTK- cells. Selection of transformants with neomycin followed by selection of the transformants in methotrexate led to a 30- to 60-fold amplification of the DHFR marker and co-amplification of the PH cDNA, with a corresponding increase in the level of PH mRNA and enzyme polypeptide. The expressed enzyme has a subunit molecular weight of 50,000 which corresponds to the W- allele of rat liver PH. PH activity was detected in the transfected cells by enzymatic measurement of the conversion of [14C]phenylalanine to [14C]tyrosine, and by growth of these cells in a tyrosine-free culture medium. Expression of rat PH in cell culture should facilitate the analysis of the biochemical properties of this enzyme.

Animals↗