PubMed HealthSearch

Biomedical subjects

M Bowman

Publications and source records attributed to M Bowman.

At least 19 recordsLinked to original sources

Molecular cloning of rat Wilms' tumor complementary DNA and a study of messenger RNA expression in the urogenital system and the brain.

In an effort to study the molecular basis of kidney development and carcinogenesis, we isolated complementary DNA clones of the rat homologue of the human Wilms' tumor gene, WT-1. When compared to the predicted sequence of the human WT-1 polypeptide, the rat WT-1 amino acid sequence is highly conserved (> 97%), except for the loss of one amino acid. In situ mRNA hybridization experiments localized WT-1 expression to the glomerular cells in the kidney during embryogenesis and the Sertoli cells of the testis. Similar to expression in humans and mice, WT-1 mRNA expression in the rat kidney and testis is developmentally regulated. In addition, two novel sites of specific high level WT-1 mRNA expression were seen. One is an area in the spinal cord where high level expression occurs throughout embryonic development. The second is the area postrema in the brain where localized expression continues through adulthood, suggesting a functional role for WT-1 in rat brain.

Amino Acid Sequence

Mutations in p53 as potential molecular markers for human breast cancer.

Based on the high incidence of loss of heterozygosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern blot analysis, immunoprecipitation, and nucleotide sequencing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. Multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studies by single-stranded conformation polymorphism analysis. We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.

Base Sequence

The CD4 molecule is not always required for the T cell response to bacterial enterotoxins.

T cells respond in a V beta-restricted fashion to bacterial enterotoxins bound to major histocompatibility complex (MHC) class II molecules. The requirement for CD4 in MHC class II-restricted T cell responses is very well established. We have assessed the role of CD4 in the T cell response to the bacterial enterotoxins Staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1. Three CD4- murine T cell hybridomas were transfected with the human CD4 molecule and assayed for interleukin 2 production in the presence of accessory cells bearing human MHC class II molecules and of the appropriate enterotoxin. The results clearly indicate that CD4- cells responded even to suboptimal concentrations of enterotoxin(s) equally well as CD4+ cells. Furthermore, expression of CD4 did not result in the acquisition of previously undetectable reactivity to enterotoxins. These results suggest that unlike the case with antigen-specific responses, formation of a T cell receptor-CD3/CD4 supramolecular complex is not always essential for T cell activation by bacterial enterotoxins.

Animals

Frequency and thoroughness of STD/HIV risk assessment by physicians in a high-risk metropolitan area.

The US Preventive Services Task Force recommends that all primary care physicians assess the sexually transmitted disease/human immunodeficiency virus (STD/HIV) risk of all adolescent and adult patients. To determine whether factors amenable to change through continuing medical education are associated with frequent and thorough STD/HIV risk assessment, a telephone survey of primary care physicians in the Washington, DC metropolitan area was conducted (n = 961). Thirty-seven percent of physicians reported regularly asking new adult patients about their sexual practices; 60% asked new adolescent patients. STD/HIV risk questioning was associated with physicians' confidence in their ability to help prevent HIV, comfort with discussing patients' sexual practices, and perception of a large STD/HIV problem in their practice. These findings suggest that continuing medical education should target improvement in physicians' sexual practice questioning skills.

Attitude of Health Personnel

Trauma during pregnancy--a review of management.

The assessment and management of 22 pregnant patients who were admitted after trauma to Westmead Hospital between July, 1987 and October, 1988 was reviewed. Thirteen of the 22 patients were victims of motor vehicle accidents. Despite the fact that an injury research unit, responsible for the clerking and review of all trauma patients, is well established at our institution, only 6 patients in this series had been assessed in this fashion. Although a number of important obstetric investigations (albeit uncommon in the accident and emergency room situation) are well described in the literature, these were not performed in a number of patients. A protocol for the management of such patients is recommended so that more standardized and appropriate care might be given to the injured pregnant patient.

Accidents, Home

Intradural herniation of a lumbar intervertebral disc.

Intradural disc herniation of an intervertebral disc is a rare occurrence. The clinical presentation varies in severity and a high level of suspicion is necessary to determine the diagnosis. This is a case report of an intradural disc herniation in a young male. A review of the literature identifying the pathophysiologic mechanisms of intradural disc herniation, diagnostic imaging techniques, and treatment is presented.

Adult

Bioconcentration of chlorinated hydrocarbons from sediment by oligochaetes.

Previously published data on the accumulation of 15 chlorinated hydrocarbons from sediment by oligochaetes have been interpreted on the basis of bioconcentration from interstitial water. Calculation of the interstitial water concentration allowed determination of uptake and clearance rate constants together with bioconcentration factors (KB) for these compounds. These three factors each exhibited a systematic relationship to the octanol/water partition coefficient (KOW). The log KB versus log KOW relationship was roughly linear over the log KOW range from 4.4 to 6.4 and displayed an increasing nonlinear deviation for log KOW values greater than 6.4. These relationships are qualitatively similar to those established for other aquatic organisms where bioconcentration from water was the mechanism involved. This suggests that interstitial water may be the phase from which lipophilic compounds in sediment are bioconcentrated by oligochaetes. An expression relating the bioconcentration factor to the biotic concentration and various sediment characteristics has also been developed.

Animals

Psychological treatment of distress, pain, and anxiety for young children with cancer.

The study compared the efficacy of hypnotic "imaginative involvement," behavioral distraction and standard medical practice for the reduction of pain, distress and anxiety in children with leukemia, during bone marrow aspirations. Two age groups of children, 3 to 6, and 7 to 10 years, were randomized to the three treatment groups. Two intervention sessions were given. At first intervention, observational ratings of distress indicated significant reductions for the younger group in the hypnotic treatment, whereas the older group achieved significant reductions in both treatment conditions for observer-rated pain and anxiety. At second intervention, all groups showed reductions and the control group appeared to be contaminated. The hypnotic method with its internal focus had an all-or-none effect, whereas distraction appeared to require that coping skills be learned over one session or more.

Anxiety

Evaluation of hospital-based aeromedical transport programs using therapeutic intervention scoring.

The number of patients transported by hospital-based aeromedical transport programs is increasing rapidly across the country. How many of these patients really need this kind of transport and how to compare the performance of different services in this regard remain controversial issues. We examined these questions in a prospective analysis of 1,081 flights in 5 aeromedical transport programs using the Therapeutic Intervention Scoring System (TISS) as the basis for an index of appropriateness. An average of 41.5% of flights in all programs were clearly appropriate according to the index, i.e., had scores associated with a 99% probability of validation by direct review. Another 34.9% of flights had a greater than 50% probability of being appropriate. From 18 to 28% of flights had scores associated with only a 20% probability of justification. Although TISS scoring, which is carried out after transfer, cannot provide a means of selecting individual patients for aeromedical transfer, a TISS-based index appears to be a simple and useful method for examining overall appropriateness of program activity, and could be used to set objective standards of appropriateness for evaluation and comparison of aeromedical programs.

Aircraft

Perinatal transmission of coxsackievirus B3 in mice.

Oral infection of pregnant mice with coxsackievirus B3 (CB3) late in gestation produced maternal viremia, which peaked three to four days after challenge, then rapidly diminished. Ninety percent of mice developed IgG antibody to CB3 by ten days after challenge. CB3 titers from placental tissue peaked at two to four days after maternal infection, but moderate titers persisted for at least eight days. Though virus could be recovered (less than 1.0-1.5 log10 pfu/g) from fetal tissue in only a small percentage (3%-13%) of pregnancies, virus could be found in some fetuses eight days after maternal infection. Despite the low rate of fetal infection, many pups born to dams infected one to eight days before delivery were either stillborn (4%-41%) or died from infection shortly after birth (14%-68%). The actual percentages depended on the time interval from infection of the dams to delivery. Maternal IgG antibody to CB3, which appeared at six to eight days after infection, protected against postnatal mortality, but did not protect against stillbirth.

Animals

Marker evolution during the development of the rat mammary gland: stem cells identified by markers and the role of myoepithelial cells.

Using monoclonal antibodies and other immunological reagents we have identified characteristic markers for various epithelial cell types within the rat mammary gland. We have followed the evolution of cell types from the emergence of mammary ducts from the epidermis in the fetus to adulthood. Throughout mammary development some cells retain a group of markers which characterize the early stages of development. We have previously suggested that these cells are the stem cells for mammary development. In the adult, these cells are present in end buds and in the myoepithelial layer of ducts. We suggest that the myoepithelial layer, which we propose should be called the "basal" layer, contains several cell types, of which two are pluripotent. It contains the stem cells for mammary development, which also are present in end buds, and a precursor of ductules and alveoli. In the ducts, basal cells are probably also the precursor of luminal cells. We propose a scheme of mammary development.

Age Factors

Distribution of developmental markers in rat mammary tumors induced by N-nitrosomethylurea.

We have examined the distribution of immunological markers in 55 intraductal carcinomas induced in rats by N-nitrosomethylurea using several different regimens of carcinogen treatment. The goal was to determine the possible relationship of the marker distribution to those existing at various stages of development of the mammary gland. We have also examined two passage lines in syngeneic rats derived from two of the tumors. The distribution of markers was not affected by the regimen of administration. The primary tumors were found to maintain the general topography of mammary ducts but with infoldings of the basal layer without accompanying stroma. We attribute this to an abnormal expression of the tendency of basal cells to migrate towards the lumen to generate luminal cells. The distribution of markers in the tumors was evaluated by identifying 13 special features of distribution that are common in tumors, using all-or-none criteria. The distribution of these features bears out the high heterogeneity of tumors in which the various features vary in a seemingly independent way. There is also heterogeneity within tumors, adjacent nodes often having different marker distributions. The distribution of the markers is related to that found in the early stages of mammary development. Because of this characteristic and of the fact that the tumors contain both basal and luminal cells, they must originate from multipotent cells, probably the stem cells present in end buds and ducts as already proposed by other work. As they develop, the tumors can both differentiate towards the adult type and dedifferentiate towards a fetal type. Of the two transplanted lines one retained the same general features of primary tumors in several passages, whereas the other evolved into a fusiform cell type with a marker distribution not seen at any stage of mammary development. Foci of similar cells were already present in the primary tumor, suggesting that the tendency to progress was already determined at an early stage. The fusiform cells are similar and probably equivalent to the fusiform cells that arise in vitro in cultures of rat mammary cancers.

Animals