Stroke rehabilitation: can we do better?
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Cerebrovascular Disorders↗
Biomedical subjects
J Young
Publications and source records attributed to J Young.
Neurosteroids: pregnenolone in human sciatic nerves.
The characterization and quantification of pregnenolone in human sciatic nerves were undertaken, following previous demonstration of the synthesis of this steroid in rat brain oligodendrocytes, to explore the hypothesis that Schwann cells may demonstrate the same biosynthetic activity. Pregnenolone was definitively identified by mass spectrometry and quantified by specific radioimmunoassay. Its concentration (mean +/- SD, 63.9 +/- 45.9 ng/g of wet tissue, n = 12) was greater than or equal to 100 times the plasma level and concentration found in tendons and muscle. No correlation was found with sex or age. Free dehydroepiandrosterone as well as sulfate and fatty acid esters of pregnenolone and dehydroepiandrosterone were also measured. Results are discussed in terms of the concept that these "neurosteroids" may be synthesized in the peripheral nervous system.
Adult↗
In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia.
We show that a highly aggressive subclone of murine BCL-1 B-lineage leukemia expresses a single 2.4-kb transcript hybridizing to the human CD19 cDNA probe and reacts strongly with the anti-human CD19 monoclonal antibodies (MoAb) B43, B4, Leu-12, and J3-119. In contrast to their strong reactivity with anti-human CD19 MoAb, BCL-1 cells show no reactivity with MoAb directed against human CD22, CD72, HLA-DR, IgD, or IgM. Western blot analysis of BCL-1 whole cell lysates with the anti-human CD19 MoAb J3-119 showed a single 69-Kd protein band, which was not detected by the negative control MoAb G19.4 (anti-CD3). In contrast to BCL-1 cells, normal BALB/c splenocytes or mouse splenocyte/myeloma hybridoma cell lines did not (1) express any transcripts that hybridized to the human CD19 cDNA probe, (2) react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts with the anti-human CD19 MoAb J3-119. Murine BCL-1 B-cell leukemia thus provides a unique model of disseminated B-lineage leukemia to evaluate the antileukemic efficacy of anti-CD19 immunotoxins. This model was subsequently used to evaluate the in vivo homing ability, pharmacokinetics, and antileukemic efficacy of B43 MoAb conjugated to the plant hemitoxin pokeweed antiviral protein (PAP). B43-PAP immunotoxin (1) showed strong and antigen-specific reactivity with BCL-1 cells, (2) promptly penetrated the spleens of leukemic mice, (3) rapidly reduced the BCL-1 leukemia burden of leukemic mice and, most importantly, (4) improved survival. Finally, B43-PAP immunotoxin was more effective against BCL-1 leukemia than 700 cGy (LD100/30) total body irradiation (TBI) followed by syngeneic bone marrow transplantation (BMT).
Animals↗
On the mechanism of inhibition of viral and vesicle membrane fusion by carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine.
The mechanism by which the hydrophobic peptide Z-D-Phe-L-PheGly inhibits membrane fusion was investigated. Differential scanning calorimetry, 2H nuclear magnetic resonance (NMR), and 13C NMR of phosphatidylcholine bilayers in the presence of Z-D-Phe-L-PheGly indicate that this hydrophobic peptide penetrates the phospholipid bilayer but does not strongly perturb the properties of phosphatidylcholine bilayers with a large effective radius of curvature. However, Z-D-Phe-L-PheGly does affect the properties of highly curved phosphatidylcholine bilayers. Small, sonicated vesicles (SUV) of dipalmitoylphosphatidylcholine (DPPC) were made in the presence and absence of Z-D-Phe-L-PheGly. At pH 4.5, the presence of Z-D-Phe-L-PheGly inhibited the formation of SUV. At pH 6.7 and 7.4, SUV could form. Once sonication ceased and the vesicles were incubated at 23 degrees C, modest growth in vesicle size occurred for pure DPPC SUV. Rapid change to large sheetlike structures occurred in the presence of Z-D-Phe-L-PheGly. Z-D-Phe-L-PheGly appeared to favor the formation of phospholipid structures with large radii of curvature. In these experiments, Z-D-Phe-L-PheGly had access to both sides of the bilayer. If Z-D-Phe-L-PheGly was added to preformed DPPC SUV (and thus present initially only in the outer leaflet of the vesicle bilayer) and incubated at 23 degrees C, only modest growth in vesicle size was observed with little difference from control values at short to intermediate incubation times.(ABSTRACT TRUNCATED AT 250 WORDS)
1,2-Dipalmitoylphosphatidylcholine↗
Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in colorectal tumors.
Kirsten-ras-revertant-1 (Krev-1/Rap1A) is a recently identified tumor suppressor gene which induces flat revertants when introduced into a variety of ras-transformed cell lines in vitro. Since 47% of colorectal carcinomas have transforming mutations in ras protooncogenes, and since Krev-1 is expressed at high levels in normal colonic mucosa, we hypothesized that inactivation at the Krev-1 locus may be necessary for transformation of colonic cells. Loss of heterozygosity is a common method of inactivation of tumor suppressor genes in colorectal tumors. Therefore, we analyzed loss of heterozygosity in 52 patients with sporadic colorectal cancer. Because Krev-1 had no previously described polymorphisms, we first identified a BclI restriction fragment length polymorphism which showed 40% heterozygosity in 50 unrelated individuals. However, only one tumor from 18 informative patients showed allelic loss at the Krev-1 locus. This suggests that loss of heterozygosity is not a common mechanism of inactivation at the Krev-1 locus in colorectal cancer. However, the results do not exclude a role for Krev-1 in the etiology of this neoplasm because inactivation may occur by other mechanisms.
Alkaline Phosphatase↗
Lymphocyte responses to DR4/1-restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19-kd Mycobacterium tuberculosis protein.
OBJECTIVE: Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1-restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1-restricted lymphocyte responses in healthy volunteers and patients with RA were determined. METHODS: Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19-kd Mycobacterium tuberculosis (MT) protein. RESULTS: 3H-thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N-terminal peptide (residues 1-20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N-terminal peptide was not a common antibody-binding site, unlike several of the other peptides. CONCLUSION: Similar responses by RA and normal PBL to a DR4/1-restricted immunodominant T cell epitope on the 19-kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1-restricted peptide immunotherapy.
Adult↗
Variation in mantle technique: implications for establishing priorities for quality assurance in clinical trials.
74 European and American radiotherapists responded to a questionnaire investigating the treatment of a patient with stage IIA non-bulky Hodgkin's disease by mantle irradiation. A consensus was present for the dose aims to involved and uninvolved lymph nodes and the acceptable incidence of late normal tissue effects. There was less agreement as to the total dose and dose per fraction required to maintain normal tissue toxicity within the agreed acceptable incidence. Variation was found in the radiation technique employed, the amount of spinal cord shielding used, the prescription point, modifications if irradiation was given after chemotherapy, and the routine recording of dose and dose per fraction to the normal tissue at risk. This descriptive survey confirms the need for well designed quality assurance programmes and indicates the areas of particular uncertainty that currently exist.
Clinical Trials as Topic↗
The role of a radiographer counsellor in a large centre for cancer treatment: a discussion paper based on an audit of the work of a radiographer counsellor.
It is widely accepted that cancer patients have unmet psychosocial needs. There are as yet few guidelines on the appropriate role of a counsellor in centres for cancer treatment. In this study the activities of a radiographer counsellor were audited to try to identify the proportion of patients who would benefit from seeing a counsellor, to estimate the cost of such a service, and to obtain indications of how the effects of counselling could be evaluated. The study suggested that 44% of patients attending for routine radiotherapy have abnormally high levels of anxiety and might benefit from counselling. The Hospital Anxiety and Depression Scale (HADS) is proposed as an objective measure of benefit. Costing and resource allocation are discussed.
Adult↗
Community based cancer support groups: an undervalued resource?
A pilot study was set up and to identify the local community based cancer support groups and to examine the links these groups and the staff of the regional and district general hospitals. The objective was to evaluate the current role of cancer support groups and identify strategies which would improve communication. Results of the study indicated that local support groups played an important role in providing support to cancer patients in the community. Hospital staff were not well informed about support groups and felt uncertain about their use as a resource for patients. There was a need to improve communication between local cancer support groups and hospital staff in order to offer a more comprehensive service to patients. Any strategies developed to improve communication depend on finding ways in which lay care and professional health care can work together. Specific recommendations were made as a result of the research and a number of initiatives undertaken, including a local directory of community resources and a forum where representatives from the local support groups can meet with hospital staff.
Communication↗
The effects of heating and devitrification on the structure and biological activity of aluminosilicate refractory ceramic fibres.
Three grades of ceramic fibre have been examined for their composition, structures and biological effect in several in vitro assay systems. The fibres were examined in the 'as-manufactured' state and after heating at 1200 and 1400 degrees C. Devitrification of the fibres at 1200 degrees C probably gave mullite crystals on the surface and caused the formation of the high-temperature form of cristobalite and, in zirconia grade fibres, the high-temperature, tetragonal form of zirconia as well. Further heating changed surface structure and led to zircon production in the zirconia fibres. Heating reduced the affinity of the fibres for the surface of V79-4 cells and lowered fibre toxicity toward these cells and towards macrophage-like cells. These changes in toxicity were not due to a reduction in the fibrous nature of the materials although they did become more brittle and powders prepared from them contained more isometric particles than those from as-manufactured materials. This suggests that the devitrification occurring during the use of these materials in high-temperature environments will not necessarily enhance their adverse biological activities despite the production of one phase of crystalline silica.
Aluminum Silicates↗
Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome.
OBJECTIVE: To determine the feasibility of utilizing a scintigraphic technique to differentiate patients with adult respiratory distress syndrome due to sepsis syndrome from control volunteers and patients with congestive heart failure. Gamma scintigraphy was compared with chest roentgenograms to predict mortality rate and morbidity in adult respiratory distress syndrome (ARDS) patients. DESIGN: Prospective study. SETTING: University hospital ICUs. PATIENTS: Thirty-five control volunteers, 19 patients with congestive heart failure, 30 patients with a diagnosis of sepsis. MEASUREMENTS AND MAIN RESULTS: All patients were infused iv with technetium 99m-labeled albumin and underwent computerized gamma-scintigraphic analysis with a portable gamma camera. Lung-to-heart ratio of tracer was calculated and expressed as the slope index. Increase in slope index indicated increased pulmonary albumin flux. Slope index was no different in controls compared with congestive heart failure patients, unless the pulmonary artery occlusion pressure (PAOP) was greater than 30 mm Hg. Patients with a diagnosis of sepsis had an overall increased slope index compared with the other groups. A subgroup of patients in the septic group had a normal slope index. Septic patients with an increased slope index had a significantly (p less than .01) longer duration of mechanical ventilation (36 +/- 5 vs. 7 +/- 1 days), spent longer in the ICU (67 +/- 9 vs. 11 +/- 1 days), and had a longer hospital stay (113 +/- 20 vs. 35 +/- 5 days) than septic patients with a normal slope index. CONCLUSIONS: Gamma scintigraphy successfully differentiated between control volunteers and patients with congestive heart failure with PAOP less than 30 mm Hg from patients with sepsis-induced ARDS. Although all of the patients with a clinical diagnosis of septic ARDS had similar impairments in oxygenation and chest roentgenograms, those patients with a significantly increased pulmonary albumin flux (greater than 2 SD above control mean) had a markedly increased morbidity.
Adult↗
Neutrophil-activating proteins in psoriasis.
Neutrophil accumulation in the epidermis is a histologic characteristic of psoriasis. We addressed the question: What is the major protein-like chemotactic principle responsible for neutrophil accumulation? Purification of proteinaceous neutrophil chemoattractants from extracts obtained from psoriatic scales by multistep high-performance liquid chromatography (HPLC) yielded three biochemically distinct polypeptides with potent neutrophil chemotactic activity. Aminoterminal amino acid sequence analysis of the quantitatively major neutrophil attractant revealed the sequence ELRXQXIKTYSK, which is identical to that of a 69 residue form of neutrophil-activating peptide-1/interleukin 8 (NAP-1/IL-8). The second major attractant showed the sequence XXVATELRXQXL . . ., which is identical to that of the gene product of the oncogene "gro" as well as "melanoma growth stimulatory activity, MGSA," whereas the third and minor neutrophil chemotaxin has an NH2-terminal sequence identical with NAP-1/IL-8. Estimation of NAP-1/IL-8-related proteins and gro/MGSA by HPLC combined with bioassay revealed a mean of 3.3 +/- 1.7 ng NAP-1/IL-8-related proteins (n = 11) and 3.2 +/- 1.9 ng gro/MGSA (n = 11) per 1 mg psoriatic scales. In normal heel callus (n = 8), these neutrophil attractants were found at concentrations below 0.02 +/- 0.01 ng/mg. The finding of more than 150-times increased amounts of both NAP-1/IL-8 and gro/MGSA in lesional psoriasis material suggest that these mitogenic as well as neutrophil- and lymphocyte-chemotactic compounds may play an important role in the pathogenesis of psoriasis.
Amino Acid Sequence↗
Changing attitudes towards families of hospitalized children from 1935 to 1975: a case study.
The introduction of 'open' visiting and family involvement in the care of hospitalized children created a revolution in the care of children in hospitals. This historical study utilized the situation at the Hospital for Sick Children, Toronto (HSC), as a case study illustrating change. Although psychological research provided a strong rationale for including families in the care of hospitalized children, change occurred slowly. In this regard, HSC was typical of many children's hospitals. However, there seemed to be a significant failure to learn from innovations elsewhere. Paediatric nurses, in particular, were slow to encourage family visiting and participation in care.
Attitude of Health Personnel↗
Phase I study of antilipopolysaccharide human monoclonal antibody MAB-T88.
Monoclonal antibody MAB-T88 is a human monoclonal immunoglobulin M antibody directed at the lipopolysaccharide of gram-negative bacteria. In this study, nine patients who were expected to become neutropenic from antineoplastic chemotherapy received an infusion of MAB-T88, three patients at each of three doses: 1, 4, and 8 mg/kg of body weight. MAB-T88 was shown to be safe, with an effective half-life in plasma of 25.4 h, and no patient developed immunoglobulin G antibody to MAB-T88.
Antibodies, Monoclonal↗
Dihydrolipoamide dehydrogenase from the halophilic archaebacterium Haloferax volcanii: characterization and N-terminal sequence.
Dihydrolipoamide dehydrogenase, a flavin disulfide reductase, has been purified and characterized from Haloferax volcanii. The enzyme is a dimer of relative mass 128,000, with an optimal activity at pH 9.0 in 1 M NaCl. Following reduction with its substrate, dihydrolipoamide, the enzyme is inactivated through covalent bond formation with the trivalent arsenical p-aminophenyl arsenoxide. The amino acid composition and the amino acid sequence of the first 49 residues of the N-terminus have been determined.
Amino Acid Sequence↗
Heterogeneity of chromogranin A-derived peptides in bovine gut, pancreas and adrenal medulla.
Chromogranin A is produced in many endocrine cell types, and is widely used as a marker in endocrine-cell pathology and secretory-cell biology. There is some evidence that it may be proteolytically processed to yield the putative pancreatic regulatory peptide, pancreastatin, and, in order to characterize the relevant pathways in gastrointestinal and pancreatic endocrine cells, we have used, in radioimmunoassay, site-directed antibodies to pancreastatin itself (L331) and to a sequence of chromogranin A immediately C-terminal to pancreastatin (L300). The latter antibody revealed three major forms of immunoreactivity of 8 kDa and five peptides of approx. 3 kDa in bovine pancreas and gut extracts. The 8 kDa peptides were characterized as chromogranin A-(248-313)-peptides, i.e. C-terminally extended forms of pancreastatin; two of the 8 kDa variants differed in two positions, confirming a polymorphism predicted from cDNA sequencing. One of the 3 kDa peptides was characterized as chromogranin A-(297-313)-peptide, i.e. the C-terminal heptadecapeptide of the 8 kDa peptide that would be liberated after cleavage to yield pancreastatin. On the basis of chromatographic studies, immunohistochemistry and the stoichiometry of different immunoreactive peptides, three different pathways of chromogranin A processing were identified: in adrenal chromaffin cells chromogranin A existed mainly as the unmodified intact protein, in pancreatic islet and gastric antral endocrine cells pancreastatin and the 3 kDa peptides were major products, but in small intestine and gastric corpus endocrine cells there was little nor no pancreastatin and the 8 kDa cleavage product predominated. There are therefore important differences in the distribution of chromogranin A-derived peptides between quite closely related populations of endocrine cells that are attributable not only to variable post-translational cleavage but also to the expression of different primary sequences. It seems possible that in different cell types chromogranin A-derived peptides might subserve a variety of different functions.
Adrenal Medulla↗
Ion channel involvement in hypoxia-induced spreading depression in hippocampal slices.
Rat hippocampal tissue slices were made hypoxic in control medium and in medium containing the ion channel blockers tetraethylammonium (TEA), 4-aminopyridine (4-AP), or tetrodotoxin (TTX). Postsynaptic evoked potentials, extracellular DC potential Vec, and in some experiments extracellular potassium concentration [K+]o were monitored in stratum pyramidale of the CA1 region. TEA (10 mM) decreased the latency of hypoxia-induced spreading depression (SD), and reduced the amplitudes of the changes in Vec and [K+]o. 4-AP (50 microM) also decreased the latency of SD but had no effect on the Vec shift. In most slices, TTX (1 microM) increased SD latency but had no effect on the Vec shift. In some slices, TTX blocked the occurrence of SD.
4-Aminopyridine↗
Suppressive effects of dehydroepiandrosterone and 3 beta-methyl-androst-5-en-17-one on attack towards lactating female intruders by castrated male mice. II. Brain neurosteroids.
Dehydroepiandrosterone (DHA) and 3 beta-methyl-androst-5-en-17-one (CH3-DHA) suppress attacks by castrated male mice towards lactating female intruders (Haug et al. Physiol. Behav. 46:955, 1989). Their effects on the concentrations of DHA, pregnenolone (delta 5P), and their sulfate ester (S) have been investigated in the brain of control and treated mice. A more than 2 fold, significant, decrease of delta 5P-S was the only change common to both steroids. DHA and CH3-DHA effects might be related to the antagonistic action of delta 5P-S on GABAA receptors.
Aggression↗