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Biomedical subjects

J Hudson

Publications and source records attributed to J Hudson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Severe aplastic anaemia in association with a unique constitutional translocation 46,XY,t(6;10)(q13;q22)c.

Severe aplastic anaemia (SAA) is an uncommon disorder which may be associated with several congenital syndromes. However, it has rarely been described in association with a constitutional karyotypic abnormality. The breakpoint of the balanced t(6:10)(q13:q22) translocation described here does not disrupt any currently recognized gene of haemopoietic or stromal importance. This report also highlights the problems inherent in the use of bone marrow transplantation (BMT) for treating multiply transfused aplastic anaemia patients.

Adolescent↗
PubMed1997

A first-generation whole genome-radiation hybrid map spanning the mouse genome.

We have assembled a first-generation anchor map of the mouse genome using a panel of 94 whole-genome-radiation hybrids (WG-RHs) and 271 sequence-tagged sites (STSs). This is the first genome-wide RH anchor map of a model organism. All of the STSs have been previously localized on the genetic map and are located 8.8 Mb apart on average. This mouse WG-RH panel, known as T31, has an average retention frequency of 27.6% and an estimated potential resolution of 145 kb, making it a powerful resource for efficient large-scale expressed sequence tag mapping. [All of the mapping data for the maps presented here have been deposited at the Research Genetics, Inc., web site and can be freely accessed and downloaded at http://www.resgen.com/.]

Animals↗
PubMed1997

Craving for cocaine in addicted users. Role of serotonergic mechanisms.

Very few studies have examined the role of serotonin (5-HT) in the modulation of craving for cocaine in cocaine-addicted persons. The authors evaluated whether the acute increase in serotonergic neurotransmission after the administration of a challenging dose of the 5-HT partial agonist meta-chlorophenylpiperazine (m-CPP) had an effect on spontaneous cocaine craving. Male inpatients (N = 31) who met DSM-III-R criteria for cocaine dependence completed 2 days of testing (separated by 48 hours) that involved the oral administration of m-CPP (0.5 mg/kg of body weight) or placebo in random order and under double-blind conditions. Patients' craving for cocaine was found to decrease significantly after the administration of m-CPP. These data could provide evidence for a modulation of cocaine craving by 5-HT systems.

Administration, Oral↗
PubMed1997

Hormonal, psychological, and alcohol craving changes after m-chlorophenylpiperazine administration in alcoholics.

To assess the serotonergic function of alcoholics, their neuroendocrine and psychological responsivities to the serotonergic partial agonist meta-chlorophenylpiperazine (m-CPP) was compared with the responsitivity of healthy subjects. The effect of m-CPP on craving for alcohol was also assessed in the alcoholics. Sixteen patients and 14 controls were tested under double-blind, placebo-controlled conditions. m-CPP (0.5 mg/kg of body weight) was given orally. Alcoholics were tested after a period of abstinence of 15 to 39 days. The two groups of subjects did not differ in their cortisol response to m-CPP, but the prolactin response of alcoholics was significantly blunted. Alcoholics reported a significantly more intense "high" feeling after m-CPP than the healthy subjects. m-CPP induced also a decreased craving for alcohol. Our data thus provide further evidence for the existence of a serotonergic dysfunction in alcoholics and a modulation of craving for alcohol by serotonergic systems.

Adult↗
PubMed1996

Antibody ligation of CD9 modifies production of myeloid cells in long-term cultures.

The KMC8.8 monoclonal antibody was made by immunizing rats with the BMS2 stromal cell clone, and was selected for further study because its ability to inhibit production of myeloid cells in Dexter cultures but not that of lymphoid cells in Whitlock-Witte cultures. The influence on myeloid progenitors might have been indirect, since the antibody did not prevent responsiveness to colony-stimulating factors in semisolid agar cultures. Furthermore, there was no inhibition, and some augmentation, of cell production when the antibody was added to established Dexter cultures. A cDNA clone that encoded the KMC8.8-recognized molecule was isolated by expression cloning and found to be identical in sequence to a previously published murine CD9 homologue. The antibody and cDNA clone were used to establish that CD9 is expressed by stromal cells, megakaryocytes, platelets, myeloid cells, and subpopulations of mature lymphocytes in mice. Treatment with the KMC8.8/CD9 antibody slightly augmented adhesion between myeloid cells and stromal cells, consistent with previous reports that this member of the tetraspan family of proteins can transmit proadhesive signals to human platelets and lymphoid cells. CD9 might participate in cell-cell interactions critical for correct orientation and movement of maturing myeloid cells in bone marrow.

Animals↗
PubMed1996

Effect of ultraviolet-B light on lymphocyte activity at doses at which normal bone marrow stem cells are preserved.

Ultraviolet B (UVB) light is known to be immunosuppressive, but, probably because of a small UVC component in the emission spectra of some of the UVB lamps used, reports vary on effective dose levels. To prevent potentially lethal graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, alloreactive donor T-cell activity must be suppressed. In this study, a narrow wavelength UVB lamp (TL01, 312 nm peak emission) was used to determine what doses of UVB were required to abolish rat lymphocyte proliferation while simultaneously preserving rat bone marrow progenitor cell and primitive hematopoietic stem cell viability. Lymphocyte proliferation, as measured by 3H-Thymidine incorporation, in response to lectin stimulation was abolished below detection at doses greater than 3,500 J/m2. When T-cell clonogenicity was measured in a limiting dilution assay, a small fraction (0.6%) was maintained at doses up to 4,000 J/m2. Cytotoxic T-lymphocyte (CTL) activity was reduced after treatment with 4,000 J/m2, but a significant level of cytotoxicity was still maintained. Natural killer cell cytolytic activity was not affected by doses up to 4,000 J/m2. At 4,000 J+m2 there was a 10% survival of colony-forming units-granulocyte-macrophage; a 1% and 4% survival of day-8 and day-12 colony-forming units-spleen, respectively; and 11% survival of marrow repopulating ability cells. Up to 25% of late cobblestone area forming cells (4 to 5 weeks), reflecting the more immature hematopoietic stem cells, were preserved in bone marrow treated with 4,000 J/m2, indicating that early stem cells are less sensitive to UVB damage than are more committed progenitor cells. Thus, a potential therapeutic window was established at approximately 4,000 J/m2 using this light source, whereby the potentially GVHD-inducing T cells were suppressed, but a sufficient proportion of the cells responsible for engraftment was maintained.

Animals↗
PubMed1996

In vivo electrochemical studies of dopamine overflow and clearance in the striatum of normal and MPTP-treated rhesus monkeys.

Rapid chronoamperometric recordings, using Nafion-coated carbon-fiber electrodes (30-90 microns o.d.), were used to investigate overflow and uptake of dopamine (DA) in the striatum of normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys. The monkeys were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging-guided sterile stereotaxic procedures were used for implantations of the electrochemical electrodes coupled with single-barrel micropipettes that were used to apply potassium or DA locally. Potassium evoked a robust overflow of DA-like electrochemical signals into the brain extracellular space in the unlesioned or normal putamen and caudate nucleus of the rhesus monkeys. In contrast, potassium did not produce any detectable changes (> 97% depletion) of DA in the MPTP-lesioned striatum. In addition, the diffusion/clearance of locally applied DA was markedly altered in the lesioned caudate nucleus and putamen compared with unlesioned striatum. Cell counts of the number of residual tyrosine hydroxylase-positive neurons in MPTP-treated monkeys, in conjunction with whole-tissue levels of DA and its metabolites, showed that the MPTP lesions produced extensive damage of the nigrostriatal DA system. These data indicate that residual dopaminergic fibers remaining after MPTP lesions are dysfunctional and have a greatly diminished capacity for high-affinity DA uptake.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

PCR amplification of short tandem repeat sequences allows serial studies of chimaerism/engraftment following BMT in rodents.

Animal models of bone marrow transplantation (BMT) allow evaluation of new experimental treatment strategies. One potential strategy involves the treatment of donor marrow with ultra-violet B light to allow transplantation across histocompatibility boundaries without an increase in graft rejection or graft-versus-host disease. A major requirement for a new experimental protocol, particularly if it involves manipulation of the donor marrow, is that the manipulated marrow gives rise to long-term multilineage engraftment. DNA based methodologies are now routinely used by many centres to evaluate engraftment and degree of chimaerism post-BMT in humans. We report the adaptation of this methodology to the serial study of engraftment in rodents. Conditions have been defined which allow analysis of serial tail vein samples using PCR of short tandem repeat sequences (STR-PCR). These markers have been used to evaluate the contribution of ultraviolet B treated marrow to engraftment following BMT in rodents without compromising the health of the animals under study. Chimaerism data from sequential tail vein samples and bone marrow from selected sacrificed animals showed excellent correlation, thus confirming the validity of this approach in analysing haemopoietic tissue. Thus the use of this assay may facilitate experimental studies in animal BMT.

Animals↗
PubMed1996

Severity of radiographic findings in hip osteoarthritis associated with total hip arthroplasty.

OBJECTIVE: The decision to perform total hip arthroplasty (THA) in patients with osteoarthritis (OA) of the hip is based largely on patients' reports of pain and disability and not on radiographic findings of OA. We determine the severity of radiographic OA and its association with disability in patients undergoing THA. METHODS: Individual radiographic features (osteophytes, joint space narrowing, sclerosis, cysts, deformity) and global severity of hip OA were assessed in 95 consecutive elderly patients with hip OA undergoing THA who were enrolled in a Patient Outcome Research Team (PORT) project. RESULTS: Eighty-seven patients (91.5%) had either severe or moderate OA in the hip to be replaced; 17% of these had a previous contralateral THA. Only 8 patients (8.4%) had mild or no signs of OA in the hip to be replaced and 4 (50%) of these patients had their opposite hip replaced previously. CONCLUSION: These data indicate that radiographic features of moderate to severe hip OA are associated with clinical findings and the necessity to perform THA in the majority of patients. Patients who have had a prior hip replacement, however, may be more likely to have a contralateral replacement done earlier (p = 0.03), before radiographic signs are evident.

Aged↗
PubMed1995

Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo.

Recently, a novel glial cell line-derived neurotrophic factor (GDNF) has been identified, cloned, and shown to have potent survival- and growth-promoting activity on fetal rat midbrain dopaminergic neurons in cell culture. In this study, we document marked and long-lasting effects on adult rat midbrain dopaminergic neurons in vivo after intracranial administration. A single injection of this factor into the substantia nigra elicited a dose-dependent increase in both spontaneous and amphetamine-induced motor activity, and a decrease in food consumption, lasting 7-10 days. Using immunocytochemistry, we found sprouting of tyrosine hydroxylase-positive neurites towards the injection site, and increased tyrosine hydroxylase immunoreactivity of the ipsilateral striatum was produced by GDNF. There was also a marked and dose-dependent increase in dopamine turnover in the substantia nigra and striatum, and in ipsilateral dopamine levels in the substantia nigra. Little or no effects of GDNF were seen on norepinephrine or serotonin levels. The neurochemical changes on dopaminergic afferents persist for at least 3 weeks after a single intracranial injection of 10 micrograms. Taken together, these data suggest that this glial cell line-derived factor has a potent influence on adult rat dopamine neurons and may have a potentially important role as a trophic factor for these neurons.

Animals↗
PubMed1994

Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo.

Fischer 344 rats were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA). Apomorphine-induced rotational behavior was used to select animals whose rotation exceeded 300 turns/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurotrophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 micrograms). The highest dose of GDNF tested produced a marked decrease in rotational behavior. This dose also produced levels of DA in the ipsilateral substantia nigra (SN) which were not statistically different from the contralateral side. Vehicle-treated animals showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggesting that GDNF may develop into a useful therapy for Parkinson's disease.

Animals↗
PubMed1993

Alternatively spliced pp52 mRNA in nonlymphoid stromal cells.

The 52-kDa phosphoprotein, also reported as lymphocyte-specific gene 1 and WP34, is transcribed as a 1.6-kb mRNA in B lymphocytes, B cell lines, and untransformed T cells. This gene encodes a cytoplasmic and plasma membrane-associated protein that is phosphorylated at a casein kinase II site and reportedly binds calcium. Based on these properties, it has been hypothesized that lymphoid form of the 52-kDa phosphoprotein protein may play a role in lymphocyte signal transduction. We show that alternatively spliced mRNA are expressed from this gene in nonlymphoid cell lines (myocytes, stromal cells, fibroblasts). These cell lines do not express the 1.6-kb lymphoid cell-specific transcript. Instead, mRNA of 2.0 and 2.8 kb are detected in varying abundance. A full-length 2.0-kb cDNA has been cloned and sequenced from the BMS2 stromal cell line by conventional screening and polymerase chain reaction-based methods. This cDNA clone, designated S37, has a single open reading frame encoding a 328 amino acid peptide. The nucleotide sequence of the S37 stromal cell cDNA is identical to that of the lymphocyte derived pp52 cDNA from the 3' poly(A) tail to the codon encoding the amino acid at residue 24. This region of the S37 cDNA clone encodes a protein that is identical to that encoded by the lymphoid pp52 cDNA and includes a casein kinase II phosphorylation site. However, the two clones differ in their 5' nucleotide sequence and their NH3 terminal amino acid sequence. This organization is consistent with alternative exon utilization. These results suggest that tissue-specific control mechanisms are used to generate different forms of lymphoid form of the 52-kDa phosphoprotein mRNA in lymphoid cells versus mesoderm-derived, nonlymphoid cell lineages.

Alternative Splicing↗
PubMed1993

Osteoblastic gene expression during adipogenesis in hematopoietic supporting murine bone marrow stromal cells.

A growing body of data suggests that the bone marrow stroma contains a population of pluripotent cells capable of differentiating into adipocytes, osteoblasts, and lymphohematopoietic supporting cells. In this work, the murine stromal cell lines BMS2 and +/+ 2.4 have been examined as preadipocytes and adipocytes for evidence of osteoblastic gene expression. Adipocyte differentiation has been quantitated using fluorescence activated cell sorting. Within 7-10 days of adipocyte induction by treatment with glucocorticoids, indomethacin, and methylisobutylxanthine, between 40% to 50% of the cells contain lipid vacuoles and exhibit a characteristic adipocyte morphology. Based on immunocytochemistry, both the adipocytes and preadipocytes express a number of osteoblastic markers; these include alkaline phosphatase, osteopontin, collagen (I, III), bone sialoprotein II, and fibronectin. Based on biochemical assays, the level of alkaline phosphatase expression is not significantly different between preadipocyte and adipocyte cells. However, unlike rat cell lines, dexamethasone exposure causes a dose-dependent decrease in enzyme activity. The steady-state mRNA levels of the osteoblast associated genes varies during the process of adiopogenesis. The relative level of collagen I and collagen III mRNA is lower in adipocyte-induced cells when compared to the uninduced controls. Osteocalcin mRNA is detected in preadipocytes but absent in adipocytes. These data indicate that osteoblastic gene expression is detected in cells capable of undergoing adipocyte differentiation, consistent with the hypothesis that these cell lineages are interrelated.

Adipose Tissue↗