Biomedical subjects

H Hall

Publications and source records attributed to H Hall.

At least 73 records · Page 4Linked to original sources

PubMed1997

[125I] beta-CIT-FE and [125I] beta-CIT-FP are superior to [125I] beta-CIT for dopamine transporter visualization: autoradiographic evaluation in the human brain.

The binding of the three dopamine transporter radioligands ([125I] beta-CIT, [125I] beta-CIT-FE, and [125I] beta-CIT-FP) was studied using whole-hemisphere autoradiography on postmortem human brains. The autoradiograms revealed an intense and homogeneous labeling of the nucleus caudatus and putamen but also to varying extent to serotonergic and noradrenergic transporters of neocortex and thalamus. The order of specificity estimated (striatum over neocortex ratios) was beta-CIT-FP > beta-CIT-FE > > beta-CIT, suggesting that beta-CIT-FE and beta-CIT-FP should be preferred for in vivo studies of the dopamine transporter in the human brain.

Autoradiography↗

PubMed1997

L1/HNK-1 carbohydrate- and beta 1 integrin-dependent neural cell adhesion to laminin-1.

We have shown recently that mouse small cerebellar neurons adhere to a short amino acid sequence of the G2 domain of the laminin alpha 1 chain via the cell surface-expressed HNK-1 carbohydrate. Therefore, we were interested in identifying glycoproteins carrying the HNK-1 carbohydrate at the cell surface of these neurons. Adhesion of small cerebellar neurons to laminin is partially dependent on Ca2+, Mn2+, and Mg2+, indicating the involvement of integrins, which were identified as beta 1, alpha 3, and alpha 6. They could be shown to bind to laminin by a beta 1-dependent adhesion mechanism. None of these subunits was found to carry the HNK-1 carbohydrate. HNK-1-immunoreactive glycoproteins were immunoprecipitated and shown to consist of predominantly one molecular species, which was identified as the neural cell recognition molecule L1. L1 was demonstrated to bind in a concentration-dependent and saturating manner to laminin. The binding could be partially inhibited by Fab fragments of monoclonal antibodies against the HNK-1 carbohydrate and against the Ig-like domains of L1. Furthermore, antibodies to the Ig-like domains of L1 and beta 1 integrin inhibited partially cell adhesion to laminin. Determination of the association of L1, beta 1 integrin, and the HNK-1 carbohydrate on the cell surface of live cerebellar neurons by antibody-induced patching and copatching revealed HNK-1 to be linked to L1, but less so to beta 1 integrin. However, only negligible association was found between L1 and beta 1 integrin. Furthermore, it could be shown that adhesion to laminin is mediated by L1/HNK-1- and beta 1 integrin-dependent mechanisms that act at least partially independent of each other.

Animals↗

PubMed1997

Improved receptor analysis in PET using a priori information from in vitro binding assays.

An accurate determination of non-specific binding is required for the analysis of in vitro and in vivo receptor binding data. For some radioligands the non-specific binding is of the same magnitude as the specific binding. Furthermore, in vitro measurements have shown that the non-specific binding can be different in different brain regions. If this is the case in a PET study for determining Bmax and Kd, a correction for the non-specific binding has to be applied. The aim of the present communication is to present a means for determining corrected Bmax and Kd with Scatchard analysis using in vitro binding studies. The influence of non-specific binding on the free and specifically bound radioligand is expressed with the aid of a correction factor, which can be calculated from measurable quantities. Introduction of the corrected free and specifically bound radioligand should give binding parameters closer to reality than previously obtained results.

Animals↗

PubMed1997

The relationship between nonorganic signs and centralization of symptoms in the prediction of return to work for patients with low back pain.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the relationship between the nonorganic signs (Waddell scores) of patients with low back pain, their response to repetitive end-range lumbar spine test movements (centralization of symptoms), and the rate of return to work at a 6-month follow-up. SUBJECTS: Patients were assessed at five locations of the Canadian Back Institute. A consecutive sample of 126 patients with low back pain, with or without referred leg pain, was selected and reviewed. METHODS: Physical therapists assessed patients' responses to repetitive test movements (centralization), as described by McKenzie, and tested the patients for nonorganic signs (Waddell scores). Therapists completed a data sheet that classified patients as either those who centralize their symptoms or those who do not centralize their symptoms and recorded their Waddell scores. Although the patients were classified at assessment, they remained in treatment. All patients followed a structured Canadian Back Institute protocol of active exercise, regardless of centralization status or Waddell score. RESULTS: The inability to centralize symptoms indicated a decreased likelihood of returning to work, regardless of the Waddell score. A high Waddell score predicted a poor chance of returning to work, regardless of the patients' ability to centralize symptoms. CONCLUSION AND DISCUSSION: A high Waddell score appears to be the best predictor of outcome, as indicated by return to work.

Adult↗

PubMed1997

Outcomes of surgeons who have undergone spine surgery.

The objective of this study was to examine the prevalence, characteristics, and outcomes of spine surgery among a membership of American orthopaedic surgeons with a particular interest in spine care [North American Spine Society (NASS)] and a general membership of Canadian orthopaedic surgeons [Canadian Orthopaedic Association (COA)]. A 25-item multiple choice questionnaire was developed and mailed to both memberships. The COA response rate was 45.9%; the NASS response rate was 45.8%. Of those who replied, 17.2% had undergone spinal surgery, and the results differed significantly between the COA at 12.9% and NASS at 21.9%. As a percentage of the total mailing, 7.7% had undergone spinal surgery. These results differed significantly between the COA at 5.9% and NASS at 9.7%. Although the surgery rate for NASS respondents was more than 1.5 times that of COA respondents, they had strikingly similar outcomes. They are a highly motivated, self-employed group who missed little work before and after having surgery.

Back Pain↗

PubMed1996

Inhibition of FGF-stimulated phosphatidylinositol hydrolysis and neurite outgrowth by a cell-membrane permeable phosphopeptide.

BACKGROUND: Activated receptor tyrosine kinases bind downstream effector molecules with high affinity. Provided that they can be introduced into cells, peptides corresponding to these high-affinity sites should be able to compete for the interaction and thereby inhibit specific signal transduction cascades. The high-affinity binding site for phospholipase C gamma (PLCgamma) on the activated fibroblast growth factor receptor (FGFR) is centred around the tyrosine at position 766 (766Tyr), and peptides corresponding to this site inhibit PLCgamma binding to the receptor in vitro. A 16 amino-acid peptide from the third helix of the Antennapedia homeodomain protein has recently been shown to be able to act as an internalization vector that can deliver other peptides into cells. Here, we have designed a peptide that contains both the internalization sequence and the FGFR high-affinity binding site for PLCgamma, and tested it in cultures of cerebellar neurons for its ability to inhibit the activation of PLCgamma by basic FGF. RESULTS: The peptide containing the FGFR high-affinity binding site for PLCgamma inhibited phospholipid hydrolysis stimulated by basic FGF with a maximal effect at 1 microg ml-1. Phosphorylation of 766Tyr was required for this effect. The phosphorylated peptide had no effect on phospholipid hydrolysis stimulated by platelet-derived growth factor, neurotrophin-3 and bradykinin. The phosphorylated peptide also inhibited neurite outgrowth stimulated by FGF, but had no effect on neurite outgrowth stimulated by agents that activate the FGFR signal transduction cascade downstream from the activation of PLCgamma. CONCLUSIONS: Cell-permeable peptides can be designed that inhibit the function of receptor tyrosine kinases. In this context we have developed a peptide that prevents the FGFR from activating PLCgamma, and have used this peptide to obtain the first direct evidence that activation of PLCgamma is required for the neurite outgrowth response stimulated by basic FGF.

Amino Acid Sequence↗

PubMed1996

Autoradiographic localization of extrastriatal D2-dopamine receptors in the human brain using [125I]epidepride.

Epidepride is a benzamide with high affinity for central D2- and D3-dopamine receptors. The anatomical distribution of [125I]epidepride binding was examined by autoradiography, using postmortem human whole-hemisphere cryosections. The density of [125I]epidepride binding sites was high in caudate nucleus and putamen. [125I]epidepride also labeled receptors in extrastriatal region such as in the pallidum, some thalamic nuclei, the neocortex, and the substantia nigra. The neocortical binding was heterogeneously distributed. In most cortical regions, binding sites were located in superficial layers (I-II). However, in basal levels of the occipital cortex, [125I]epidepride binding was located in a deeper layer, probably corresponding to layer V. Competition studies indicated that most of the [125I]epidepride binding represented predominantly D2-dopamine receptors, in striatal as well as in extrastriatal regions. The presence of extrastriatal D2-dopamine receptor populations is of particular interest for research on schizophrenia and antipsychotic drug action.

Aged↗

PubMed1996

Autoradiographic localisation of D3-dopamine receptors in the human brain using the selective D3-dopamine receptor agonist (+)-[3H]PD 128907.

The selective D3-dopamine receptor agonist 4aR, 10bR-(+)-trans-3,4,4a, 10b-tetrahydro-4-[N-propyl-2,3-3H]-2H,5H-[1] benzopyrano[4,3-b]-1,4-oxazin-9-ol ([3H]PD 128907) was used to visualise D3-dopamine receptors in whole hemisphere cryosections from post-mortem human brain. [3H]PD 128907 has an 18- to 40-fold selectivity for D3- over D2-dopamine receptors as compared to a 7- to 24-fold selectivity of the more commonly used ligand [3H]7-OH-DPAT. [3H]PD 128907 accumulated markedly in the nucleus accumbens and in the ventral parts of caudate nucleus and putamen, with a slightly heterogeneous (patch-matrix like) distribution. The binding in the lateral parts of caudate nucleus and putamen was much less dense. No binding was obtained in any other regions. A very high proportion of [3H]PD 128907 was specifically bound, as judged from the low binding remaining in the presence of the D2/D3-dopamine receptor antagonist raclopride. This gives the ligand a potential for the detection of low density D3-dopamine receptors in the human brain. The binding obtained with [3H]PD 128907 was qualitatively similar to that using [3H]7-OH-DPAT in the presence of GTP. However, [3H]7-OH-DPAT labelled, in contrast to [3H]PD 128907, also D3-dopamine receptors in neocortex. The new compound [3H]PD 128907 appears to be a suitable radioligand for autoradiographic examination of the D3-dopamine receptor localisation in the human brain, and should also be useful for pharmacological studies of this receptor subtype.

Adult↗

PubMed1996

Directional changes in neutrophil adherence following passive resting versus active imagery.

This study was designed to determine whether increases or decreases in neutrophil adherence could be achieved following a self-regulation (relaxation/imagery) intervention. Fifteen subjects were randomly assigned to one of three conditions. Two experimental groups employed imagery focussed on either increasing or decreasing neutrophil adherence. Subjects had two weeks of self-regulation practice (4 total training sessions) prior to blood drawings. A third group of control subjects had the same number of resting sessions without imagery training. All subjects had blood samples collected before and after either 30 minutes of self-regulation or resting practice for two sessions. Pulse and peripheral finger temperature measures were taken before and after the blood samples. Both experimental groups demonstrated decreases in neutrophil adherence, and the control showed a tendency toward increases in this measure. The psychophysiologic data for the control group was suggestive of a relaxation response. The experimental group that attempted to increase neutrophil adherence demonstrated psychophysiologic responses that were contrary to relaxation. We concluded that an active cognitive exercise or process is associated with decreases in neutrophil adherence irrespective of the exercise. In contrast, relaxation without an active imagery exercise was associated with increases in neutrophil adherence. The results of this study are discussed in terms of behavioral engineering of directional immune changes.

Adolescent↗

PubMed1996

Review: a role for the FGF receptor in the axonal growth response stimulated by cell adhesion molecules?

Cell adhesion molecules (CAMs) have been shown to stimulate axonal growth. The molecular basis of this response has been extensively studied and a range of agents that promote or inhibit CAM stimulated axonal growth have now been identified. These studies have led to the suggestion that following homophilic and/or heterophilic interactions CAM specific signal transduction pathways are activated which are directly responsible for promotion of axonal growth. In this review we will suggest that the axonal growth response stimulated by three CAMs (NCAM, N-cadherin and L1) can be operationally divided into a number of phases. During the first phase homophilic and/or heterophilic binding between the CAMs expressed on the axonal growth cone and cellular substrate take place. This is followed by an interaction of the neuronal CAMs with the fibroblast growth factor receptor (FGFR), leading to receptor activation by autophosphorylation. This results in the recruitment and activation of additional effector molecules via interactions of their SH2 domains with the activated receptor. In this context the key event in terms of neurite outgrowth appears to be the activation of phospholipase C gamma (PLC gamma) which sets into motion a second messenger cascade that ultimately leads to a modification, most likely by phosphorylation, of cytoskeletal elements that are involved in growth cone motility.

Animals↗

PubMed1995

A test to measure lift capacity of physically impaired adults. Part 1--Development and reliability testing.

STUDY DESIGN: Two laboratory studies and one field study evaluated the safety and test-retest reliability of a new test of lift capacity. The first two studies were conducted in a carefully controlled laboratory setting. The first study investigated the safety and intra-rater reliability of the EPIC Lift Capacity test protocol with healthy adult subjects. The second study assessed the safety and inter-rater reliability of the test with disabled subjects. The third study was conducted in the field with 65 evaluators and investigated the safety and intra-rater reliability of the test with healthy adult subjects. OBJECTIVE: To assess the safety and reliability of a new test of lift capacity. SUMMARY OF BACKGROUND DATA: A new test of lift capacity has been developed. Test development occurred within the context of ergonomic standards and guide-lines of the major professional associations and public agencies that govern test development in the United States. METHODS: In study no. 1, 26 healthy subjects participated. In study no. 2, 14 disabled subjects participated. In study no. 3, 318 healthy subjects participated. After subjects underwent basic screening and warm-up, the EPIC Lift Capacity test was administered. One to 2 weeks later, the test was administered again. Correlations between the times of testing were calculated. RESULTS: No subjects were injured. Hamstring soreness the next day that resolved without complication was reported by some healthy subjects. None of the disabled subjects reported new symptoms. CONCLUSION: The safety and reliability of the EPIC Lift Capacity test was adequately demonstrated in a laboratory setting and across multiple field sites with evaluators who have varying types and degrees of professional preparation.

Adult↗

PubMed1995

Spine rehabilitation. Secondary and tertiary nonoperative care.

To achieve desirable behavioral outcomes, physicians treating spinal pain patients should be aware of appropriate algorithms for conservative care. Lower cost secondary rehabilitation can be effective if deconditioning, severity of physical symptoms, surgical equivocation, or psychosocial barriers to recovery are not present. Patients who have extended disability in excess of 6 months, recognized psychosocial barriers (depression, substance abuse, personality disorders, secondary gain), or severe deconditioning have a better prognosis with tertiary care.

Humans↗

PubMed1995

Controversy. Low back school. Education or exercise?

Few interventions have conclusively changed the natural history of low back pain with respect to recovery once an episode has begun, or have prevented future recurrence. Variations of the low back school, an educational approach, have become increasingly popular but their efficacy remains controversial. Dr. Hall is emphatic that patient education is a less than perfect but nonetheless an important approach. Dr. Hadler believes that these programs re-enforce the misconception that low back pain is an injury rather than a commonly occurring life event, such as the flu, and should be handled but not overtreated. He offers a more tempered opinion.

Exercise Therapy↗

PubMed1995

Variability in D2-dopamine receptor density and affinity: a PET study with [11C]raclopride in man.

The variability of D2-dopamine receptor binding parameters in man was determined using Positron Emission Tomography (PET) and [11C]raclopride. A saturation analysis based on five PET-experiments was performed in each of ten men and ten women. The mean density of D2-dopamine receptors (Bmax) was 28 +/- 6.9 pmol/ml (mean +/- S.D.) and the apparent affinity (Kdapp) 9.1 +/- 1.9 pmol/ml. The Hill coefficient was in all subjects close to unity (nH: 0.999 +/- 0.020), thereby indicating binding to a homogeneous class of receptors. No significant differences between males and females were found in Bmax or Kdapp. The interindividual difference in Bmax was statistically significant (alpha = 0.01). The difference in Kdapp was not significant. Upregulation of the receptor density (Bmax) has been widely discussed as a mechanism for increased dopaminergic neurotransmission in schizophrenia. This study indicates that receptor density varies considerably in a group of healthy subjects.

Adult↗

PubMed1995

Distribution of messenger RNAs for D1 dopamine receptors and DARPP-32 in striatum and cerebral cortex of the cynomolgus monkey: relationship to D1 dopamine receptors.

Messenger RNAs for the D1 dopamine receptor and dopamine- and cyclic AMP-regulated phosphoprotein of relative mass 32,000 (DARPP-32) were examined by in situ hybridization in the cynomolgus monkey brain. The messenger RNA distribution was compared to the distribution of D1 dopamine receptors using [3H]SCH 23390 autoradiography. In the caudate nucleus and putamen, D1 dopamine receptor messenger RNA-positive cells were unevenly distributed. Clusters of cells with an approximately three-fold higher intensity of labeling, as compared to surrounding regions, were found. Some of these D1 dopamine receptor messenger RNA intensive cell clusters in the caudate nucleus appeared to some extent to be matched to regions of higher intensity of [3H]SCH 23390 binding. The distribution of cells expressing DARPP-32 messenger RNA in the caudate nucleus and putamen was found to be non-clustered. In neocortical regions, cells of different sizes expressing D1 dopamine receptor messenger RNA were present in layers II-VI. D1 dopamine receptor messenger RNA-positive cells were most abundant in layer V. Unexpectedly, no DARPP-32 messenger RNA signal was detected in neocortex. Chronic SCH 23390 administration did not change the relative levels of messenger RNAs for the D1 dopamine receptor and DARPP-32 or [3H]SCH 23390 binding as measured by quantitative image analysis. The clustered distribution of D1 dopamine receptor messenger RNA is in contrast to that of DARPP-32 messenger RNA. This suggests that D1 dopamine receptors may play a more significant role in regulating DARPP-32 function in patch regions as compared to matrix regions. D1 dopamine receptor messenger RNA-expressing cells could also be visualized in several layers of the primate neocortex, implying that dopamine acts through D1 dopamine receptors within functionally different neuronal circuits of the neocortex.

Animals↗

PubMed1995

Effect of clozapine and risperidone on 5-HT2 and D2-dopamine receptor binding in the post-mortem human brain. An autoradiographic study.

Effects of the antipsychotics risperidone and clozapine on 5-HT2 and D2-dopamine receptor binding were examined using [3H]N-methylspiperone ([3H]NMSP) and in vitro receptor autoradiography on human whole hemisphere cryosections. The 5-HT2 receptor antagonist ketanserin and the D2-dopamine receptor antagonist raclopride were used as references. [3H]NMSP binding was observed in caudate nucleus, putamen, and cerebral cortex indicating binding to D2-dopamine and 5-HT2 receptors. Risperidone and clozapine counteracted the binding to both receptor types. This was in contrast to raclopride, which selectively blocked the D2-dopamine receptors in the basal ganglia, and ketanserin, which selectively blocked the 5-HT2 receptors in the cerebral cortex. Risperidone (100 nM and 10 microM) blocked up to 90% of [3H]NMSP binding to both receptor types, whereas the blocking capacity of clozapine (10 microM) was lower (approximately 60%). The lack of total blockade of D2-dopamine receptors is in line with results obtained in with [11C]raclopride and positron emission tomography studies of clozapine treated human subjects. However, autoradiographic studies of clozapine competition of [3H]raclopride binding show total displacement of the binding at high clozapine concentrations, thus contradicting the PET results with [11C]raclopride, as well as the autoradiographic results obtained with [3H]NMSP. In conclusion it can be stated that pharmacological concentrations of the two drugs clozapine and risperidone block a large proportion of D2-dopamine receptors and 5-HT2 receptors in the human brain. Moreover, the study shows the usefulness of human whole hemisphere autoradiography for the study of interaction of drugs with different central neurotransmitter receptors.

Adult↗

PubMed1995

Synthesis and binding properties of [3H]NNC 12-0781, a new radioligand for the dopamine reuptake system.

The tritiated dopamine reuptake inhibitor [3H]NNC 12-0781 ([1-[2-(bis(4-fluorophenyl)-methoxy)-ethyl]-4-(3-(2-furanyl)-2,3-[3H] - propyl)-piperazine) was radiolabelled in one step starting from 1-[2-(bis(4-fluorophenyl)-methoxy)-ethyl]-4-(3-(2-furanyl)-2-propenyl)- piperazine, using tritium gas and PdO as catalyst. The radiochemical purity of [3H]NNC 12-0781 was higher than 99% after HPLC purification with a specific radioactivity of 21 Ci/mmol. [3H]NNC 12-0781 bound specifically to rat striatum in vitro at +4 degrees C with a Kd of 1.76 nM and Bmax of 587 fmol/mg tissue. The nonspecific binding was about 10% at Kd. At +37 degrees C no acceptable binding was observed. The association of [3H]NNC 12-0781 thus has the characteristics of a radioligand for the dopamine transporter in vitro at +4 degrees C.

Animals↗

PubMed1995

[O-methyl-11C]beta-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: preparation, autoradiography, metabolite studies, and positron emission tomography examinations.

beta-CIT-FP [N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-11C]beta-CIT-FP ([11C]beta-CIT-FP) was prepared by O-alkylation of the free acid with [11C]methyl iodide. The total radiochemical yield of [11C]beta-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was > 99%, and the specific radioactivity at time of injection was about 37 GBq/mumol (1000 Ci/mmol). Autoradiographic examination of [11C]beta-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [11C]beta-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of beta-CIT, indicating that striatal radioactivity following injection of [11C]beta-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [11C]beta-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [11C]beta-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

Animals↗