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Biomedical subjects

D M White

Publications and source records attributed to D M White.

At least 37 records · Page 2Linked to original sources

Increased neurite outgrowth of cultured rat dorsal root ganglion cells following transection or inhibition of axonal transport of the sciatic nerve.

Dissociated dorsal root ganglion cells (DRGs), taken from rats 2 weeks after sciatic nerve transection, have an increase in the percentage of cells with neurites compared to DRGs taken from normal animals. This study examines the possible factors that may contribute to the nerve injury-induced increase in neuritogenesis. Topical application of the local anaesthetic, bupivicaine, either to the nerve trunk prior to transection or to the proximal nerve stump for 2 weeks had no effect on the increased neurite outgrowth induced by nerve transection. Neurite outgrowth was also not influenced by administration of either nerve growth factor (NGF) via the femoral artery into normal rats or anti-NGF antiserum to the proximal nerve stump. Inhibition of axonal transport by topical application of vinblastine, however, induced a significant increase in neurite outgrowth compared to untreated controls. In addition, vinblastine-treated animals also develop hyperalgesia to mechanical stimulation and transganglionic labelling of sensory neurons with choleragenoid-horseradish peroxidase shows that the area of termination of myelinated sensory neurons in the spinal cord expands into lamina II. The results suggest that nerve injury-induced increase in neurite outgrowth is not dependent on NGF nor nerve impulses generated at the site of injury and supports the view that the absence of an inhibitory factor(s), that in normal animals may regulate neuronal outgrowth.

Anesthetics, Local↗

Mechanism of prostaglandin E2-induced substance P release from cultured sensory neurons.

Hyperalgesia (tenderness) is a prominent feature of the inflammatory response. It is thought to be mediated, in part, by humoral factors such as prostaglandin E2, which act directly to sensitize primary afferent nociceptors. Prostaglandin E2 also interacts with nociceptors to induce a release of substance P, which can feed back to enhance the inflammatory response and also induce a long-lasting hyperalgesia. This study examined the mechanism of prostaglandin E2-induced substance P release from cultured adult rat dorsal root ganglion cells. Release studies were performed by bathing cultures with Tyrode solution +/- test agents and substance P was measured by radioimmunoassay. Substance P release induced by 100 nM prostaglandin E2 was inhibited by the prostaglandin antagonist, SC19220, and modulated by the guanine nucleotide analogs, guanosine-5'-[gamma-thio]triphosphate and guanosine-5'-[beta-thio]diphosphate, which stimulate and inhibit, respectively, stimulatory G-proteins. Substance P release was found to be Ca(2+)-dependent, requiring an influx of Ca2+ via N-type voltage-sensitive Ca2+ channels, since it was blocked by omega-conotoxin, but not nifedipine. The results suggest that prostaglandin E2 acts via a G-protein-coupled binding site on dissociated dorsal root ganglion cells to induce a Ca(2+)-dependent release of substance P, and provide further insight into the possible mechanisms underlying hyperalgesia associated with inflammation.

Animals↗

Vasoactive intestinal polypeptide and neuropeptide Y act indirectly to increase neurite outgrowth of dissociated dorsal root ganglion cells.

Recent studies suggest that rearrangement of synaptic circuitry of primary afferent neurons in the spinal cord may contribute, in part, to hyperalgesia that is often associated with peripheral nerve injury. This study of cultured adult rat dorsal root ganglion cells examined whether vasoactive intestinal polypeptide and neuropeptide Y, which are up-regulated in sensory neurons following nerve transection, possibly contribute to the morphological alterations induced by nerve injury. Neurite outgrowth of dissociated dorsal root ganglion cells was examined two weeks following either sciatic nerve transection or intrathecal administration of test agents via osmotic pumps. Dissociated cells taken from rats with transected sciatic nerve or following intrathecal administration of either vasoactive intestinal polypeptide or neuropeptide Y had a significant increase in the percentage of cells with neurites as compared to dorsal root ganglion cells taken from normal animals. Intrathecal administration, into rats with nerve lesion, of the vasoactive intestinal polypeptide and neuropeptide Y antagonists, vasoactive intestinal polypeptide(10-28) and alpha-trinositol, respectively, significantly attenuated the nerve injury-induced increase in neurite outgrowth. Vasoactive intestinal polypeptide and neuropeptide Y had no influence on neurite outgrowth when applied to normal dissociated dorsal root ganglion cells, however, when added to cells co-cultured with spinal cord explants, both peptides significantly increased the percentage of cells with neurites. K252a, a protein kinase inhibitor, attenuated the trophic action of neuropeptide Y, but not that of vasoactive intestinal polypeptide. The action of vasoactive intestinal polypeptide on neurite outgrowth was attenuated by the protein kinase A inhibitor, the Rp-isomer of adenosine-3',5'-cyclic monophosphorothioate. The results suggest that the peptides may contribute, indirectly, to the nerve injury-induced increase in neurite outgrowth of sensory neurons via separate spinally-derived neurotrophic factors and the study provides further insight into the possible mechanisms underlying hyperalgesia associated with nerve injury.

Animals↗

Successful induction ovulation and completed pregnancy using recombinant human luteinizing hormone and follicle stimulating hormone in a woman with Kallmann's syndrome.

The induction of ovulation in women with hypogonadotrophic hypogonadism requires follicle stimulating hormone (FSH) for follicular growth and both FSH and luteinizing hormone (LH) to induce optimal follicular steroidogenesis. The development of human recombinant FSH and LH means that individually tailored doses of both hormones can be used with the aim of inducing unifollicular ovulation. This report describes the use of recombinant human FSH and LH for the induction of ovulation and conception in the second cycle of treatment, and subsequently a successfully completed pregnancy in a woman with Kallmann's syndrome.

Adult↗

Interstitial deletions of the short arm of chromosome 4 in patients with a similar combination of multiple minor anomalies and mental retardation.

Interstitial deletions of chromosome 4 have been described rarely and have had variable presentations. We describe the phenotypic characteristics associated with interstitial deletion of the p14-16 region of chromosome 4 in 7 patients with multiple minor anomalies in common, and with mental retardation. A review of published cases of interstitial deletions of the short arm of chromosome 4 is provided. These deletions present a distinct phenotype which is different from that of Wolf-Hirschhorn syndrome.

Abnormalities, Multiple↗

Detection of minimal residual disease in childhood acute lymphoblastic leukaemia using fluorescence in-situ hybridization.

Using centromere-specific probes and a fluorescence in-situ hybridization (FISH) technique in cases of childhood hyperdiploid acute lymphoblastic leukaemia (ALL), cells with extra copies of chromosomes can be differentiated from normal cells by their extra signals in both metaphase and interphase nuclei. In this way the entire cell population, not only those cells in division, can be analysed, thereby providing a valuable technique not only for determining leukaemia cell karyotype at diagnosis but also for the detection of minimal residual disease (MRD). We have conducted 161 analyses of remission bone marrow aspirates (BMs) in 13 children with hyperdiploid ALL. Slides were analysed blind and in parallel to 35 control samples. Control BMs showed very low numbers of trisomic cells (mean +/- 2 x SD = 0.13 +/- 0.34%). MRD was detected in 5/13 cases of ALL investigated while on chemotherapy. One out of five newly diagnosed cases and all three relapse cases of ALL had significantly raised levels of hyperdiploid cells in day 28 BMs. The presence of detectable disease in day 28 BMs suggests the need for larger studies to find whether this data is of prognostic value.

Child↗

Use of standardized activities of daily living rating scales in spinal cord injury and disease services.

OBJECTIVE: Although standardized activities of daily living (ADL) rating scales offer advantages in reliability and consistency of reporting, the literature has revealed that most occupational therapists tend to use informal assessments and reporting methods. This study investigated the use of standardized ADL rating scales by occupational therapists who treat patients with spinal cord injury and disease (SCI/D). METHOD: Fifty-two SCI/D rehabilitation sites were selected by stratified random sampling, and surveys were completed by the occupational therapist in each site who worked most extensively with patients with SCI/D: Occupational therapists at 49 of the sites completed the survey. RESULTS: Survey results indicated that 68% of the respondents tend not to use standardized ADL rating scales in their work with SCI/D patients. Of those who used standardized ADL rating scales, the Functional Independence Measure (FIM) was more widely used than any other. Most respondents learned about this measure on the job. Many of the respondents indicated that a limitation of the FIM was its inability to detect progress in their patients with SCI/D: DISCUSSION: The results indicate that although widely used, the FIM may need to be supplemented by other standardized ADL rating scales in order for a therapist to objectively document the progress made by patients with SCI/D: To be able to choose the most appropriate assessment tools, students and practicing therapists need to be educated in a variety of standardized ADL rating scales.

Activities of Daily Living↗

Catecholamine-induced mechanical sensitization of cutaneous nociceptors in the rat.

C-Fiber mechanoheat (C-MH) nociceptors from the saphenous nerve were studied, in control rats and in rats that underwent surgical sympathectomy. Intradermal injection, alone, of either norepinephrine (NE) or the calcium ionophore, A23187, did not affect mechanical threshold. The combination of A23187 and NE, however, significantly decreased mechanical threshold. In the presence of the alpha 2-adrenergic antagonist, yohimbine, or the cyclooxygenase inhibitor, indomethacin, C-MHs were not sensitized by the combination of NE + A23187. One week after surgical sympathectomy, the number of C-MHs sensitized by NE + A23187 was significantly reduced. In summary, NE appears to sensitize nociceptors indirectly. These data are compatible with the suggestion that a sympathetic postganglionic neuron-dependent release of prostaglandins mediates the sensitization. NE appears to act at an alpha 2-adrenergic receptor, only in the presence of an increased intracellular Ca2+.

Action Potentials↗

Assessment of proliferative activity in leukaemic bone marrow using the monoclonal antibody Ki-67.

AIMS: To investigate proliferative activity in leukaemic and lymphomatous bone marrow infiltrates and to assess the feasibility of transport of specimens among institutions. METHODS: Proliferative activity in bone marrow trephine cryosections from 99 patients with non-Hodgkin's lymphoma (NHL), 23 patients with acute myeloid leukaemia (AML), 11 with acute lymphoblastic leukaemia (ALL), and two with acute undifferentiated leukaemia (AUL) was investigated. Infiltration was seen in 52 out of 99 cases of NHL on bone marrow cryosections. A score was devised to assess pathological infiltrates in bone marrow trephine cryosections using the monoclonal antibody Ki-67. This method of scoring gave a measure of non-erythroid proliferative activity. RESULTS: Mean Ki-67 positivity in bone marrow infiltrates in 31 low grade B cell lymphomas (Kiel classification) was 0.3% before and 4.7% after treatment, 16.4% in seven high grade B cell lymphomas, and 17.8% in 12 peripheral T cell lymphomas. In 48 cases of NHL, bone marrow cryosections had not been infiltrated, and in all but one case the percentage of Ki-67 positive cells in normal marrow was less than 3%; the remaining case showed coexistent myelodysplasia and 8% bone marrow Ki-67 positivity. In eight cases of common ALL at diagnosis, the mean Ki-67 positivity in marrow cryosections was 24.9%, significantly higher than the 2.4% Ki-67 positivity seen in AML (p < 0.05). One of the two cases of common ALL with less than 1% Ki-67 positivity was refractory to treatment. CONCLUSIONS: Proliferative activity of erythroid elements in the bone marrow varies greatly. Immunostaining of bone marrow cryosections using Ki-67 permits accurate assessment of non-erythroid proliferative activity in lymphomas and leukaemia. High grade B cell lymphomas and peripheral T cell lymphomas invading the marrow have very similar mean proliferative activities. Such levels of proliferation are of the same order as those seen in common ALL, but much higher than those seen in AML.

Adult↗

PTA supervision.

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Personnel Management↗

Mechanism of oxyhemoglobin-induced release of endothelin-1 from cultured vascular endothelial cells and smooth-muscle cells.

Release of endothelin-1 from cultured endothelial cells can be induced with oxyhemoglobin (oxyHb). The present study was conducted to explore whether oxyHb affects the release of endothelin-1 and the induction of endothelin-1 messenger ribonucleic acid (mRNA) and to examine the mechanism whereby oxyHb induces endothelin-1 production in cultured vascular smooth-muscle cells as well as in cultured endothelial cells. Oxyhemoglobin produces concentration-dependent (0.1 to 10 microM) and time-dependent (0 to 24 hours) increases in immunoreactive endothelin-1 in conditioned medium from bovine arterial endothelial cells. Oxyhemoglobin induces immunoreactive endothelin-1 in rat aortic smooth-muscle cells in the same fashion, although the rate is 30-fold less than that of endothelial cells. This promoting effect is much higher than that of other stimulators such as thrombin and phorbol 12-myristate 13-acetate. Northern blot analysis of total RNA from endothelial cells also showed endothelin-1 mRNA induction. Staurosporine, a protein kinase C (PKC) inhibitor, inhibited oxyHb-induced endothelin-1 production in both vascular endothelial and smooth-muscle cells, whereas an increase of intracellular cyclic adenosine monophosphate (cAMP) by forskolin or an addition of 8-bromo-cAMP only inhibited this effect in smooth-muscle cells. These findings suggest that oxyHb-induced endothelin-1 production in endothelial cells is regulated by PKC, and in smooth-muscle cells by both PKC and the cAMP-dependent pathway. The production of endothelin, the most potent vasoconstrictor, in both vascular endothelial and smooth-muscle cells by oxyHb may have significance in the pathogenesis of cerebral vasospasm.

8-Bromo Cyclic Adenosine Monophosphate↗

Structure and chromosomal localization of the human gene for a brain form of prostaglandin D2 synthase.

We have cloned and characterized the human gene for the 21-kDa brain form of prostaglandin D2 synthase. The gene was isolated from a human genomic lambda library and spans 3600 base pairs. It consists of seven exons and six introns. Southern blot analysis indicates that there is a single copy of the gene in the haploid genome. The transcriptional start site was mapped to a G residue 74 base pairs 5' of the ATG initiation codon. A TATA box-like element (ATAAATA) is situated 21 base pairs upstream of the mRNA start site. The gene was mapped to chromosome 9 bands q34.2-q34.3. The gene bears close resemblance to the genes for murine major urinary protein and ovine beta-lactoglobulin.

Amino Acid Sequence↗

Risk level, knowledge, and preventive behavior for human papillomaviruses among sexually active college women.

During the past decade, there has been mounting scientific evidence linking human papillomavirus (HPV) with cervical cancer and, at the same time, a great increase in physician consultations for HPV infections. HPV infection risk factors include multiple sex partners, early age at first intercourse, history of sexually transmitted diseases (STDs), and smoking. This study surveyed 263 sexually active college women and concluded that (1) they are at considerable risk for contracting HPV, (2) they lack awareness of HPV, and (3) they are not practicing preventive behaviors that could reduce their risk of HPV and its serious consequences.

Adolescent↗

Eicosanoids, but not tachykinins, excite C-fiber endings in rat sciatic nerve-end neuromas.

Normal nociceptors are sensitized by hyperalgesic mediators such as eicosanoids and tachykinins. The possibility that these mediators contribute to hyperalgesic pain associated with neural injury was investigated by examining their effects on the excitability of injured afferent nerve endings. In amounts that sensitize normal nociceptors and are hyperalgesic in normal skin, the eicosanoids prostaglandin I2 (PGI2), and 8(R),15(S)-dihydroxyicosatetraenoic acid (8(R),15(S)-diHETE) both excited some C-fibers in chronic neuromas of rat sciatic nerve. In contrast, the selective tachykinin-receptor agonists septide and senktide did not excite C-fibers. None of the mediators affected A-fibers. We conclude that PGI2 and 8(R),15(S)-diHETE may contribute to post-injury pain and hyperalgesia by an action on injured afferent endings.

Animals↗