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Biomedical subjects

J E Hudson

Publications and source records attributed to J E Hudson.

18 recordsLinked to original sources
PubMed2004

Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?

Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural-derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic-derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three-drug treatment) animals. The triple-suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CD antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human-specific antibodies (anti-human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, "neuralization," and migratory features of HUCB-derived cells.

Age Factors↗
PubMed2004

Green fluorescent protein bone marrow cells express hematopoietic and neural antigens in culture and migrate within the neonatal rat brain.

Finding a reliable source of alternative neural stem cells for treatment of various diseases and injuries affecting the central nervous system is a challenge. Numerous studies have shown that hematopoietic and nonhematopoietic progenitors derived from bone marrow (BM) under specific conditions are able to differentiate into cells of all three germ layers. Recently, it was reported that cultured, unfractionated (whole) adult BM cells form nestin-positive spheres that can later initiate neural differentiation (Kabos et al., 2002). The identity of the subpopulation of BM cells that contributes to neural differentiation remains unknown. We therefore analyzed the hematopoietic and neural features of cultured, unfractionated BM cells derived from a transgenic mouse that expresses green fluorescent protein (GFP) in all tissues. We also transplanted the BM cells into the subventricular zone (SVZ), a region known to support postnatal neurogenesis. After injection of BM cells into the neurogenic SVZ in neonatal rats, we found surviving GFP+ BM cells close to the injection site and in various brain regions, including corpus callosum and subcortical white matter. Many of the grafted cells were detected within the rostral migratory stream (RMS), moving toward the olfactory bulb (OB), and some cells reached the subependymal zone of the OB. Our in vitro experiments revealed that murine GFP+ BM cells retained their proliferation and differentiation potential and predominantly preserved their hematopoietic identity (CD45, CD90, CD133), although a few expressed neural antigens (nestin, glial fibrillary acdiic protein, TuJ1).

Animals↗
PubMed1991

Metabolism of the aldose reductase inhibitor ALO1567 in man.

1. The metabolism of the aldose reductase inhibitor, ALO1567, was studied in man. The major biotransformation pathway was aromatic hydroxylation followed by glucuronide conjugation. 2. Hydroxylation occurred at several positions on the fluorene ring. The major metabolite was identified as the 7-hydroxy analogue of ALO1567 and three minor metabolites were characterized as positional isomers of the 7-hydroxy metabolite. 3. Oxidative defluorination and metabolism on the hydantoin ring were also indicated as minor pathways. 4. The capacity of normal subjects to oxidize ALO1567 was indicated by the urinary ratio of the parent drug to the 7-hydroxy metabolite after daily oral administration of 100 mg and 200 mg of ALO1567. Most subjects having higher ALO1567 plasma concentrations showed higher ratios.

Adult↗
PubMed1982

Crithidia fasciculata: a catalase-containing trypanosomatid sensitive to nitroheterocyclic drugs.

Crithidia fasciculata, which contains high levels of a cytosolic catalase, is sensitive to inhibition by at least two nitroheterocyclic drugs, Nifurtimox and MK 436, both of which are also active against Trypanosoma cruzi. Drug sensitivity is not enhanced in organisms containing reduced levels of catalase. The ultrastructural lesions in T. cruzi produced by nitroheterocycles, especially the swelling and gross vacuolation of the mitochondria, are seen also in C. fasciculata. These results are not consistent with the hypothesis that the action of drugs such as Nifurtimox on T. cruzi involve hydrogen peroxide accumulation as a result of the absence of catalase.

Animals↗
PubMed1980

Synthesis of [8,9-2H2]apomorphine and [1,3,8,9-2H4]apomorphine for PMR, 13C-NMR, and mass spectral studies.

Methods are described for the preparation of [8,9-2H2]apomorphine and [1,3,8,9-2H4]apomorphine based on reaction of apomorphine in trifluoroacetic acid-d. The mass spectral properties of these compounds and of the O,O-bis(heptafluorobutyrate) ester and the O,O-bis(tert-butyldimethylsilyl) ethers of apomorphine, using electron impact and chemical ionization, are reported. [1,3,8,9-2H4]Apomorphine was used to elaborate the 13C-NMR chemical shifts of the proton-bearing carbons of apomorphine.

Apomorphine↗
PubMed1977

The degradation and turnover of fucosylated glycoproteins in the plasma membrane of a neuroblastoma-cell line.

When monolayer cultures of neuroblastoma N2a cells were prelabelled with [(3)H]fucose to steady state, and then reincubated in complete medium in the presence of unlabelled 40mm-l-fucose, there was a rapid metabolism of fucosylated cellular macromolecules and the specific radioactivity of the acid-insoluble material decreased by 22% within 2h. After this period of time the remaining radioactive glycoproteins appeared to be more stable and the rate of loss of specific radioactivity markedly decreased. Since fucose is known to be associated predominantly with plasma-membrane components, the analysis of fucosylated glycoproteins was characterized in plasma-membrane fractions by polyacrylamide-gel electrophoresis. Two experimental approaches were used to measure glycoprotein degradation and turnover in the cell-surface membranes. In one set of experiments, with a similar incubation procedure to that used with intact cells, three membrane components were rapidly degraded (150000, 130000 and 48000 daltons), but another surface glycoprotein (68000 daltons) appeared to be more slowly metabolized than the mean rate of glycoprotein degradation. The relationship of the degradation of membrane glycoproteins to their turnover was analysed by dual-label experiments that used both [(14)C]fucose and [(3)H]fucose. Glycoproteins of the surface membrane of neuroblastoma cells were found to turn over at heterogeneous rates. The components mentioned above that exhibited significantly rapid rates of degradation, were also shown to turn over more rapidly than the average surface component. In addition to the membrane components detected by the use of only [(3)H]fucose, dual-label experiments illustrated that numerous surface glycoproteins were metabolized more rapidly or slowly than most of the cell-surface constituents.

Cell Line↗
PubMed1977

Rapidly metabolized glycoproteins in a neuroblastoma cell line.

The metabolism of neuroblastoma cell glycoproteins was examined using L-E13H]fucose. Incubation of monolayer cultures with [3H]fucose resulted in a rapid uptake of the radioactive precursor and its incorporation into acid-insoluble macromolecules. Less than 3% of the [3H]fucose that was isolated from neuroblastoma cells by trichloroacetic acid precipitation was associated with glycolipids. The metabolism of fucosylated macromolecules was studied in cells which were labelled to a steady state, and then reincubated under conditions which limited reutilization of the radioactive precursor (40 mM unlabelled fucose). During reincubation of the cells, we observed a rapid metabolism (27% by 2 h) of the prelabelled macromolecules which stabilized within a cell generation time to give an overall rate of turnover of 9%. This rapid loss of radioactivity from the cells was not due to exocytosis since less than 4% of the [3H]-fucose was lost into the media as macromolecules during a 5 h reincubation period. The presence of 40 mM fucose in the media did not affect cell growth until after 24 h of incubation or cellular protein synthesis until after 15 h of incubation. When the metabolism of neuroblastoma cell glycoproteins was measured in the presence of 1.8 - 10(-4) M cycloheximide, there appeared to be a less rapid decrease in cell-associated specific activity, and an increased reutilization of [3H]fucose. Although the major proportion of the radioactivity remained as e13H]fucose, extensive incubation of neuroblastoma cells with this radioactive precursor led to increased amounts of tritium associated with other cellular components; However, a rapid rate of glycoprotein metabolism could also be demonstrated with cells incubated with [14C]fucose. This eliminated the possibility that the above results were restricted to the tritiated precursor and merely a reflection of hydrogen-tritium exchange.

Cell Line↗
PubMed1976

Synthesis and turnover of plasma-membrane proteins and glycoproteins in a neuroblastoma cell line.

A kinetic analysis of the appearance of 14C-labelled proteins in the surface membranes isolated from exponentially growing neuroblastoma cells (N2a) showed that the total membrane proteins reached a steady-state specific radioactivity in 18-20 h. However, examination of individual protein bands resolved by sodium dodecyl sulphate-urea-polyacrylamide-gel electrophoresis illustrated that differences in the kinetics of specific surface-membrane proteins could be detected. Although most of the protein bands reached a steady-state specific radioactivity at a time similar to that for total membrane proteins, at least two bands (mol. wt. 180000 and 130000) attained the steady-state within 8-10 h. It was shown by the use of dual-labelling techniques that these two protein bands turned over in the surface membranes of neuroblastoma N2a cells at least 180 and 150% faster than the total membrane protein. These two proteins were glycosylated and located on the outer surface of the cells, since they were labelled with radioactive carbohydrates and readily removed by treatment of the intact neuroblastoma cell with proteinases.

Cell Line↗
PubMedDate not supplied

Teflon buttress inhibits recanalization of uncut stapled bowel.

The uncut Roux limb operation is designed to have the benefits of a Roux limb but still have electrical continuity from proximal to distal bowel, thus eliminating the risk of Roux stasis syndrome. The main complication has been recanalization of the uncut staple line leading to bile reflux. This study aims to employ a new technique, which will not allow recanalization of an uncut staple line but will not interfere with normal bowel myoelectric activity. Fourteen mongrel dogs, 25 to 35 kg, underwent a midline laparotomy under general anesthesia. An uncut staple line was placed 25 cm from the ligament of Treitz. In seven animals an uncut staple line alone was placed, and in the other seven animals the bowel was stapled between a sandwich of Teflon reinforcing strips such that the staples were held on both sides of the bowel by the Teflon. A jejunojejunostomy was placed 6 cm proximal to the staple line. Insulated bipolar electrical leads were placed around the staple line. After the electrical leads were monitored 2 days to 3 months postoperatively for bowel myoelectric activity, The animals were killed and the operative sites inspected. No animal suffered morbidity or mortality from the procedure. All seven unreinforced staple lines recanalized and all seven reinforced staple lines remained competent. The duodenal pacemaker potentials were transmitted through the staple line in five animals (3 controls and 2 with Teflon reinforcement) with in 1 week postoperatively. The uncut staple line does not reliably transmit the duodenal pacemaker potentials. The staple line does not recanalize when it is reinforced with a permanent material, increasing the utility of the "uncut" Roux limb operation.

Action Potentials↗
PubMedDate not supplied

A profile of Canadian hospital-based palliative care.

This article describes the characteristics of hospice-based palliative care programs in Canada, based on a sampling of respondents, teams, programs, and hospitals. This report is an outgrowth of a study of social services in Canadian, hospital-based palliative care programs. One hundred eighty-five hospitals were polled between December 1987 and March 1988, using a mailed-out questionnaire. One hundred sixty programs replied, a response rate of 86.5 percent.

Canada↗