Biomedical subjects
Publications and source records attributed to C Jackson.
The health of the nation white paper has been widely welcomed as a clear shift in NHS policy towards health promotion. But will the strategy achieve real improvements in the health of those who need help most? What part can health visitors and school nurses expect to play?
Explore the source record for details and available documents.
Explore the source record for details and available documents.
NHS employers must take positive steps to increase the number of women in senior management posts, the NHS management executive has ordered. It has even set up a women's unit. Cath Jackson talks to caroline Langridge, head of the unit, and to some of the women who have made it to the top.
Many severely overweight women find it difficult to follow conventional exercise programmes. Salisbury health visitors Rosalind Griffith and Pauline Sharp run weekly 'Swim-slim' sessions at the local hospital swimming pool where overweight women, too embarrassed to go to their local baths on their own, exercise together to lose weight and gain confidence to tackle social isolation and depression.
Explore the source record for details and available documents.
To many health visitors they are a threat. To others they are a unique and invaluable resource. Cath Jackson talks to the health visitors and women involved in two projects pioneering community mother programmes in England.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The fragile X syndrome, a common X-linked form of mental retardation and autism, affects females as well as males. Previous work has shown that approximately 35% of heterozygotes (women who carry the fragile X gene) demonstrate cognitive impairment. Thirty-two girls, 18 years or younger, who demonstrate the fragile X chromosome were evaluated and compared with 19 sisters who do not demonstrate the fragile X chromosome. Evaluations included a physical examination, behavioral assessment, and intelligence testing. Significant differences (in intellectual, behavioral, and physical features) were seen between the two groups. Twenty-five percent of fragile X-positive girls had an IQ in the mentally retarded range (IQ less than 70) and 28% had an IQ in the borderline range (70 to 84). Prominent ears, shyness, and poor eye contact were significant findings in fragile X-positive girls compared with fragile X-negative girls. Thirty-one percent of the fragile X-positive girls had significant attentional difficulties and most of these girls were successfully treated with stimulant medication. The majority of fragile X-positive girls in this study demonstrated significant behavioral and developmental problems which required identification and appropriate treatment. Pediatricians and health care providers should be aware of the frequency and manner with which fragile X affects females in order to initiate cytogenetic studies and treatment when indicated.
An investigation of the mechanism of action of the antitumour agent trimelamol has established that it is an efficient interstrand DNA cross-linker in vitro, comparable to nitrogen mustards such as melphalan. Studies have shown that the cross-linking reaction is acid-catalysed but, unlike the nitrogen mustards, only partially reversible after treatment with piperidine. The bisalkylation (cross-linking) reaction appears to be concerted, and no "second arm" reaction has been detected. The results of thermal denaturation studies are consistent with general DNA binding, and suggest a preference for GC-rich sites. The acid-catalysed reaction of trimelamol with a model nucleophile (thiophenol) has also been investigated and an adduct resulting from displacement of the three carbinolamine functions has been isolated and characterized.
The stability of trimelamol (N2,N4,N6-trimethylol-N2,N4,N6-trimethylmelamine) a synthetic carbinolamine-containing antitumor drug, has been studied. Two major degradation pathways have been characterized and a unified mechanism proposed to rationalize the chemistry involved. One degradation pathway involves the consecutive loss of hydroxymethylene units by elimination of formaldehyde until the parent trimethylmelamine (4) results. An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products. This pathway was shown to follow first-order kinetics at all pH values studied at both 18 and 37 degrees C. The second pathway involves the coupling of two trimelamol molecules via a methylene bridge to form bis(trimelamol) (6) which had been previously referred to in the literature as a "polymer". This reaction is acid catalyzed and temperature dependent. Bis(trimelamol) is virtually water insoluble and adheres strongly to glass surfaces. Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature. The data reported here are relevant to both the formulation and clinical administration of trimelamol, and may contribute to an understanding of mechanism of action and future analogue development studies.
A number of new intracellular renal flush solutions have been found to be more efficacious than Collins-2 (C-2) solution in extending organ viability during simple cold storage. However, the mechanism of action of these solutions remains poorly understood. To delineate better underlying intracellular mechanisms, we studied a modified, simple, hypothermic, intracellular (340 mOsm/kg) flush solution (PB-2). The development of PB-2 solution is based on the ability of some of its individual components to minimize ischemic adenine nucleotide (AN) catabolism and endothelial post "reperfusion injury." Preliminary results in 10 canine autorenal transplants show a significant (P less than 0.02) improvement in renal recovery and viability (recipient posttransplant inulin clearance and survival) after 50 h of cold storage compared with 10 canine kidneys similarly preserved using conventional C-2 flush solution. High performance liquid chromotography (HPLC) studies show a significant (P less than 0.01) loss of AN using C-2, while PB-2 was associated with regeneration of AN within 45 min of reperfusion. Magnetic resonance spectroscopy using phosphorus 31 (31P-MRS) showed more high energy phosphorus metabolites (phosphomonoester and nicotinamide-adenine-dinucleotide phosphate: P less than 0.001) at 50 h cold storage using PB-2 compared with C-2. Electron micrographs (EM) revealed normal microcapillary morphology for the PB-2 group; however, moderate vascular red and white blood cell clumping was observed in the C-2 group. Characterization of the basic preservation mechanisms by HPLC, 31P-MRS, and EM studies indicates that PB-2 solution enhances renal preservation by diminution of both reperfusion injury and the loss of intracellular high energy metabolites that are necessary for viability.
Mouse embryo cultures derived in serum-containing medium undergo growth crisis or senescence after fewer than 20 population doublings, followed by the emergence of genetically altered, polyploid 'immortalized' cells capable of growing indefinitely. Serum-free mouse embryo (SFME) cells, derived in medium in which serum is replaced with growth factors and other supplements, do not exhibit growth crisis or gross chromosomal aberrations when cultured for well over 100 population doublings and display other unique properties. We examined culture conditions and physiological factors affecting karyotypic stability in long term cultures of SFME cells derived from several mouse strains. Cloning SFME cells consistently isolated colonies with altered karyotype, even when the clones were derived from parent cultures with no karyotypic alterations. After 140-200 population doublings in vitro, the percentage of SFME cells showing hyperdiploidy or structural chromosomal abnormalities increased, although the modal chromosome number remained diploid. SFME cells transformed with molecularly cloned oncogenes did not show alterations in karyotype beyond that expected from the clonal origins of these cells, indicating that malignant transformation of SFME cells does not result in general karyotypic instability.
The morphogenetic processes responsible for the initial phase of gastrulation in sea urchin embryos are not known. Here we report observations of the size and position of clones of cells derived from horseradish peroxidase (HRP)-injected mesomeres and macromeres. The displacement of these clones during the initial phase of gastrulation suggests that involution is a mechanism involved in primary invagination. Experiments with embryos marked with vital dyes indicate that movements occur only during a brief phase coincident with the invagination of the vegetal plate. Counts of cells derived from HRP-injected mesomeres and macromeres suggest it unlikely that localized growth in the vegetal plate is involved in gastrulation. An analysis of changes in cell shape during the initial phase of gastrulation indicates that there is a stage-dependent shift from cells being columnar to having their apices skewed toward the vegetal plate and an increase in the proportion of cells having basal processes during gastrulation. When embryos are grown in the presence of monoclonal antibodies to the apical lamina or monovalent fragments of these antibodies, the initial phase of gastrulation is delayed and they form partial exogastrulae. Analysis of embryos marked with HRP indicate that the antibody treatments interfere with the cellular movements observed in untreated embryos. We conclude that directed movements of cells within the blastoderm, probably employing tractoring on components of the hyaline layer, cause the buckling of the vegetal plate and displacement of presumptive endoderm cells seen during the initial phase of gastrulation.
Explore the source record for details and available documents.
Cryptococcus neoformans is a pathogenic yeast causing disease predominantly in immunosuppressed patients. C. neoformans is acquired by the pulmonary route, where the alveolar macrophage (AM) is a resident mechanism of host defense. The ability of rat AM to be activated by products of the immune response for enhanced anticryptococcal effect has not previously been demonstrated. Rat AM could be activated in vitro for anticryptococcal activity by medium conditioned by concanavalin A-stimulated splenic lymphocytes. A monoclonal antibody that neutralizes interferon-gamma (IFN-gamma) inhibited the macrophage-activating activity of lymphokine-containing medium (LCM). Further, recombinant IFN-gamma activated AM for anticryptococcal activity. The concentration of IFN-gamma in LCM, determined by enzyme-linked immunosorbent assay, was equivalent to the range of concentrations of recombinant IFN-gamma which activated AM. Thus, IFN-gamma was necessary and sufficient for optimal macrophage activation by medium conditioned by proliferating lymphocytes. Lipopolysaccharide could not enhance the anticryptococcal activity produced by optimal concentrations of LCM or IFN-gamma but did augment the effects of submaximal stimulation. Both LCM and recombinant IFN-gamma increased the percentage of macrophages with cell-associated cryptococcus, suggesting that activation of AM enhanced the adhesion or uptake of cryptococcus. We speculate that inadequate availability of lymphokines such as IFN-gamma may result in the immunodeficient state in hosts unable to generate an appropriate response to cryptococcal antigens. Administration of lymphokines such as IFN-gamma to immunosuppressed hosts might circumvent the defect in cell-mediated immunity.
Explore the source record for details and available documents.