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Biomedical subjects

J Walker

Publications and source records attributed to J Walker.

At least 307 records · Page 17Linked to original sources

The immediate effects of different light doses for photodynamic therapy of endobronchial tumors.

The immediate effects of different power densities and light dosages were determined on 77 sites of endobronchial tumors in 28 patients. All received 2 mg/kg of dihematoporphyrin ether 2 days prior to photodynamic therapy (PDT). Light (630 nm) was delivered with a tunable dye laser system through quartz fibers modified at the delivery end to disperse the light perpendicular to the axis of the fiber. The degree of obstruction, tumor consistency, edema, exudate, bleeding, amount of relief of obstruction, and complications were estimated before and at the end of treatment and toilet bronchoscopy. The authors found no difference in the effect of power densities of 400 mW/CF or 500 mW/CF when compared to the same total light dosage. However, 700 mW/CF produced coagulation of fibrin collection on fibers. By the end of the treatment, bleeding tumors did not bleed enough to prevent removal, although they were bleeding prior to PDT. The only complication during or after the increased light dosages was the formation of exudate. Hard tumors became soft and edematous by the end of the treatment permitting immediate removal of some tumors. At the time of discharge, the authors achieved greater than 50% reduction of obstruction, that is, complete and partial responses, in 64% of the patients with 200 J/CF, 71% with 300 J/CF, 82% with 400 J/CF, 77% with 500 J/CF, and 100% with 700 J/CF. Overall, they observed a 74% response, again, complete and partial response, at discharge.

Adult↗

Lymphocyte subpopulations in pyogranulomas of caseous lymphadenitis.

Pyogranulomas of ovine caseous lymphadenitis (CLA) are encapsulated lesions resulting from infections with Corynebacterium pseudotuberculosis, a bacterial pathogen able to grow within macrophages. Immunohistology of CLA lesions showed a band of lymphocytes lining the inside of the collagen capsule in intimate contact with necrotic tissue, the intracapsular lymphocytes being organized into three layers. The innermost layer, immediately adjacent to the central necrotic tissue consisted of a narrow band of MHC class II staining macrophages. Cells staining for CD4, CD8 and gamma delta T cell markers were unevenly distributed throughout the lymphoid layer, tending to be more numerous immediately external to the macrophage layer. The intracapsular lymphoid tissue contained a high proportion of CD8+ lymphocytes (CD4:CD8, 1.5:1) and of gamma delta lymphocytes (CD4:CD8:gamma delta, 1:0.7:0.8). External to the T cell-rich zone and adjacent to the surrounding collagen capsule was a dense band of cells, a proportion of which stained atypically for CD45R and were tentatively identified as B cells. CD8+ and gamma delta+ T cells showed similar distributions and their relative abundance, compared with CD4+ T cells, was a distinguishing feature of the CLA lesion. Staining for factor VIII-related antigen clearly showed endothelial venules throughout the intracapsular lymphoid tissue. The presence of endothelial venules and the organized architecture of the lymphoid tissue teleologically argues that lymphocytes are continually recruited into chronic CLA lesions and play an important role in the ongoing disease process.

Animals↗

Coordination of low birthweight seven-year-olds.

The coordination and laterality of a group of 171 seven-year-old children, free from major disability, with a birthweight of 2,000 g or less, were examined and compared with those of normal birthweight peers. More low birthweight children were left-handed and of mixed or undetermined hand, foot and eye dominance. Left-handedness may adversely affect some areas of performance of normal birthweight but not of low birthweight children. Low birthweight children performed significantly less well in tests of both fine and gross motor coordination. Girls tended to perform better than boys in fine motor tests. In the low birthweight group there was a correlation between IQ and coordination.

Child↗

The renal vascular response to mild and severe haemorrhage in the anaesthetized rat.

1. In order to document the characteristics of the renal vascular response to blood losses of varying severity, Inactin-anaesthetized rats were subjected to a haemorrhage of 5, 10, 15 or 20 ml (kg body weight)-1, while a fifth group (control rats) remained unbled. Radioactive microspheres (diameter 10 microns) were used to determine cardiac output, total renal blood flow and the distribution of blood flow within the kidneys; measurements were made before and 5-120 min after haemorrhage. 2. In control animals none of the variables studied changed significantly during the experimental period. 3. Immediately after haemorrhage there were reductions in arterial pressure and cardiac output which were roughly proportional to the severity of haemorrhage. Arterial pressure recovered to some extent during the next 30 min, then stabilized; cardiac output recovered only slightly. 4. Total renal blood flow fell to an extent dependent on the degree of haemorrhage, with no evidence of subsequent recovery. The approximate reductions in renal blood flow were 2% (n.s.), 15%, 30% and 50% after bleeds of 5, 10, 15 and 20 ml kg-1, respectively. Renal vascular resistance increased consistently only in the groups bled 15 and 20 ml kg-1. When renal blood flow was expressed as a fraction of cardiac output, it increased during the period immediately after haemorrhage, indicating some degree of 'protection' of the renal circulation in the face of hypotension. 5. Measurements of intrarenal blood flow indicated a significantly reduced flow to the superficial cortex after every degree of haemorrhage. Inner cortical flow was less affected and fell significantly only in the groups bled 15 and 20 ml kg-1; blood flow to the mid-cortex was intermediate.

Anesthesia↗

Standards of care and practice: a vital link in quality assurance.

In the critical care unit setting, a quality assurance program is based on the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) ten-step model for monitoring and evaluation. The addition of nursing standards of patient care and standards of nursing practice to that ten-step model provides the vital link between patient expectations, staff performance, and quality assurance in that unit.

Critical Care↗

Five cases of neurocysticercosis diagnosed in Sydney.

Cysticercosis, once rare in Australia, is now more frequently diagnosed. This change reflects the countries of origin of new immigrants and the destinations of Australians travelling. Five cases of neurocysticercosis diagnosed at Westmead Hospital in Sydney are described. Two involved Australians, a father and son who had visited eastern and southeastern Asia 10 years before presentation. The other three included immigrants from Chile and India and a visitor from Timor. Ages ranged from 5 to 57 years. Three individuals presented after focal seizures involving the upper limb, one had a long standing history of neurological dysfunction and one suffered from persistent headaches. In all cases computed tomographic scanning (CT) or magnetic resonance imaging (MRI) revealed cystic brain lesions and three of the five were seropositive as well. Four were treated with praziquantel and in one the lesions regressed significantly following treatment. However, the lesion in one case had decreased in size prior to treatment and that in the untreated individual also became smaller.

Adult↗

Hookworm folliculitis.

A case of persistent folliculitis in a 21-year-old man was demonstrated to be due to Ancylostoma caninum larvae. Treatment with oral thiabendazole was curative. Cutaneous larva migrans may be due to A caninum, but this presentation appears to be unique. The literature concerning etiology and pathogenesis of larva migrans is discussed with reference to this case.

Adult↗

Scanning electron microscopic study of microaneurysms in the diabetic retina.

We describe the clinical and pathologic appearance of the retinal microcirculation in a patient with a 22-year history of diabetes mellitus. A vascular cast of one eye was prepared and studied with scanning electron microscopy. The three-dimensional views obtained give insight into the pathogenesis of microaneurysms.

Aged↗

Factors affecting nucleosome structure in transcriptionally active chromatin. Histone acetylation, nascent RNA and inhibitors of RNA synthesis.

The nucleosomes of transcriptionally active genes can be separated from those of inactive genes by affinity chromatography on organomercury-agarose (Hg-agarose) columns. The basis for this separation is the difference in accessibility of the sulfhydryl groups of histone H3 and certain non-histone proteins in active and inactive chromatin. A new procedure distinguishing between different modes of binding of transcriptionally active nucleosomes to the Hg-agarose column has been applied to study several factors which might influence the binding reaction. Nucleosomes that bind to the column because of salt-labile associations with SH-reactive non-histone proteins, such as the high-mobility-group proteins, HMG-1 and HMG-2, were released by adding 0.5 M NaCl to the eluting buffer. The remaining nucleosomes, in which reactive histone H3 thiol groups can bind covalently to the organomercury, were then displaced from the column by 10 mM dithiothreitol. Both Hg-agarose-bound fractions contain the transcriptionally active DNA sequences of the cell, but inactive nucleosomes, such as those containing alpha-globin DNA, pass through the column. The histones of both Hg-agarose-bound fractions have significantly higher levels of acetylation than do histones of the unbound fraction, but the content of tri- and tetra-acetylated H3 and H4 is significantly higher in the nucleosomes with reactive H3 thiols. The rate of turnover of histone N-acetyl groups is also far greater in the Hg-agarose-bound nucleosomes than in the unbound nucleosomes. Although the overall levels of histone acetylation can be increased significantly by incubating HeLa cells in the presence of the deacetylase inhibitor, 5 mM sodium butyrate, this treatment has little if any effect on the total number of nucleosomes retained on the Hg-agarose column. However, the ability of Hg-agarose chromatography to detect localized changes in chromatin structure is evidenced by an 11-fold increase in the Hg-agarose binding of nucleosomes containing the DNA of the butyrate-inducible alkaline phosphatase gene, compared to the Hg-agarose-bound nucleosomes of control cells. Although nascent RNA chains are present in the Hg-agarose-bound nucleosomes released by dithiothreitol, binding of the SH-reactive nucleosomes to the Hg-agarose column is not dependent on the presence of proteins associated with nascent RNA chains, since binding does not decrease following removal of the nascent transcripts by ribonuclease treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylation↗

Nafenopin, a hypolipidemic and non-genotoxic hepatocarcinogen increases intracellular calcium and transiently decreases intracellular pH in hepatocytes without generation of inositol phosphates.

Addition of nafenopin (30-300 microM to 45Ca2+ preloaded cultured hepatocytes caused a rapid and concentration-dependent increase in 45Ca2+ efflux in a manner similar to vasopressin, as evidenced by the loss of radioactivity from the cells. In contrast to vasopressin, addition of nafenopin to [3H]inositol prelabelled hepatocytes in culture did not increase [3H]inositol phosphate production. When added simultaneously with vasopressin, nafenopin inhibited the vasopressin-stimulated [3H]inositol phosphate production. In hepatocyte suspensions isolated from rats treated for 1 week with a carcinogenic dose of nafenopin (1000 ppm in their daily food) the incorporation of [3H]inositol into the phosphoinositide fraction, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, was much less than that in hepatocytes isolated from untreated rats. The vasopressin-stimulated [3H]inositol phosphate production was also decreased. Experiments with hepatocyte suspensions preloaded with Ca2+ or pH sensitive fluorescent indicators demonstrated that addition of nafenopin caused an increase in intracellular free Ca2+ and transient acidification of the cells. The increase in [Ca2+]i was decreased by only about 25% when extracellular calcium was removed indicating that nafenopin mainly mobilizes Ca2+ from intracellular stores. The recovery to basal pH was amiloride-sensitive indicating the importance of Na+/H+ exchange in pH recovery after intracellular acidification. Amiloride also inhibited DNA synthesis induced by nafenopin and by epidermal growth factor in cultured hepatocytes; but this effect occurred concomitantly with inhibition of basal DNA synthesis. We suggest that hepatic Ca2+ mobilization induced by nafenopin may play an important role in the mechanism by which nafenopin exerts its physiological as well as its tumour promotive activity upon chronic treatment with carcinogenic doses.

Animals↗

Impact of childhood cancer on return to normal schooling.

Most of the research into the psychosocial impact of treatment for cancer in children has concentrated on effects on the family rather than on the children's return to school. Thus parents and teachers were questioned about the problems experienced by 117 children who returned to school after spending time in hospital. The children comprised 51 with cancer and two groups of control children (34 with chronic diseases such as renal disease and cardiac conditions and 32 with orthopaedic conditions such as thoracic scoliosis, club foot, and injuries resulting from trauma). Children in all three groups experienced problems on returning to school, the greatest number and variety occurring in the children treated for cancer and the fewest in the children with orthopaedic conditions. The variety of physical problems was greatest and the variety of academic problems was least, with psychological and behavioural problems intermediate. Several problems seemed to be related to drug treatment. Several children missed a considerable amount of full time education. Many teachers were unsure of the academic expectations and physical capabilities of children returning to school. To facilitate a smooth return to school for a child with cancer improved liaison is needed between the hospital, school, and home during the child's absence and teachers need to be better informed.

Adolescent↗

Affinity chromatography of mammalian and yeast nucleosomes. Two modes of binding of transcriptionally active mammalian nucleosomes to organomercurial-agarose columns, and contrasting behavior of the active nucleosomes of yeast.

The reasons for the selective binding of nucleosomes from transcriptionally active genes to the organomercurial-agarose columns have been investigated. At least two modes of binding are identified by a new two-stage elution procedure that discriminates between nucleosomes which are retained by the Hg-column because of their salt-labile associations with SH-reactive non-histone proteins, and nucleosomes in which a conformational change has made the thiol groups of histone H3 accessible to SH-reagents. The first class is released from the column in 0.5 M NaCl; the second class is eluted in 10 mM dithiothreitol which displaces the bound H3-thiols. In mammalian cells, both classes of Hg-bound nucleosomes are enriched in the DNA sequences being transcribed at the time, and their histones H3 and H4 are hyperacetylated. In yeast cells, in which histone H3 lacks cysteinyl residues, only a small fraction of nucleosomes binds to the mercury column, and it has no enrichment of DNA sequences derived from the actively transcribed GAL, HIS4, and ACT1 genes. Since few nucleosomes remain on the column after elution in 0.5 M NaCl, the bound nucleosomes of yeast are retained primarily because of salt-labile associations with thiol-reactive nonhistone proteins. Thus, the presence of histone H3-thiol groups appears to be essential for the mercury binding of the second class of nucleosomes which, in mammalian cells, is derived from the transcriptionally active genes. The results support models of reversible nucleosome unfolding during transcription in mammalian cells to reveal previously inaccessible H3-SH groups, and they also indicate that other thiol-containing proteins, including high mobility group 1 and 2, become closely but transiently associated with the chromatin subunits during their transcription.

Acetylation↗

First record of human acanthocephalan infections in Australia.

Two cases of asymptomatic acanthocephalan infections in infants are described. We believe this is the first report from Australia of infection with these parasites in humans. Their clinical, epidemiological and biological significance is discussed.

Acanthocephala↗

Action of cyclosporin A on the tapeworm Hymenolepis diminuta in mice.

Cyclosporin A (CsA), administered in 5 daily subcutaneous doses of 50 mg/kg to MF1 mice immediately following infection with Hymenolepis diminuta enhanced parasite growth relative to controls. Drug administered at 24 h intervals for 10 days, and thereafter every 48 h to MF1 and CBA/Ca mice infected with H. diminuta, increased worm survival and growth, delayed host-mediated expulsion of the parasite and enabled some worms to develop to patency. Worm survival and weight both increased in a dose-dependent manner following daily CsA treatment of infected CBA/Ca and BALB/c mice (0-150 mg/kg CsA/day). Delay in parasite elimination was accompanied by increased frequency of worm-attachment in the anterior small intestine (MF1 mice given 5 daily doses of CsA [0-150 mg/kg] following infection); posteriad migration of worms was restricted in a dose-dependent manner. The data presented contrast markedly with the action of the same drug on H. microstoma in mice. Thus CsA treatment acts in opposing ways on two closely related parasites in the same host; this possibly reflects the mechanistic antagonism between immunosuppression and anthelmintic activity. This paper reports the first use of a specific T cell-suppressive drug on H. diminuta in the mouse, implicating the role of T cells in protective immunity to this parasite.

Animals↗