Biomedical subjects

B Dean

Publications and source records attributed to B Dean.

At least 91 records · Page 5Linked to original sources

PubMed1994

The development of a method to measure [3H] dopamine uptake by washed platelets provides no evidence for circulating inhibitors of platelet dopamine uptake in schizophrenia.

Altered [3H] dopamine uptake by platelet-rich plasma (PRP) has been reported in some subjects with schizophrenia (Rotman et al 1980; Dean et al 1990). As platelet dopamine uptake was measured using PRP, it was not possible to determine if the changes in schizophrenia were intrinsic to the platelet or due to plasma factors. Furthermore, the constraints of plasma as a medium for platelet suspension has hindered the study of the physiological requirements of platelet dopamine uptake. A method is now reported that allows platelets to be suspended in a controlled medium while preserving the dopamine uptake mechanism of the platelet. Dopamine uptake by platelets in a controlled medium was dependent on temperature, energy, sodium, and chloride. Furthermore, plasma from subjects with schizophrenia and schizophreniform disorder did not significantly alter [3H] dopamine uptake by platelets compared to the effect of plasma from control subjects. Hence, these data provide no evidence for a circulating inhibitor of platelet [3H] dopamine uptake in plasma from subjects with schizophrenia.

Blood Platelets↗

PubMed1993

Significant correlation between 14C-5-HT uptake by and 3H-paroxetine binding to platelets from healthy volunteers.

The lack of correlation between 5-HT uptake by platelets and the ability of platelet membrane to bind antidepressant drugs, particularly imipramine, has been reported. However, more recently it has been suggested that 3H-paroxetine could be a better drug with which to study the platelet 5-HT uptake mechanism in disease states. We have therefore compared the ability of platelet-rich plasma (PRP) from normal individuals to take up 5-HT with the ability of platelet membranes to bind paroxetine. A significant correlation was apparent between the Vmax of 14C-5-HT uptake by PRP and the Bmax of 3H-paroxetine binding to platelet membrane from 30 individuals (r = 0.6468, p = 0.0001). Furthermore, this correlation was highly significant in the 20 female (r = 0.7768, p = 0.00006) but not in the 10 male volunteers. There was also a significant association between Vmax and Bmax and the month of blood sampling but this did not totally account for the correlation between Vmax and Bmax. The simultaneous measurement of 5-HT uptake by PRP and paroxetine binding to platelet membranes from both depressed patients and matched controls should be carried out to confirm and extend these findings.

Adult↗

PubMed1993

Synthesis of multivalent beta-lactosyl clusters as potential tumor metastasis inhibitors.

A beta-lactosyl residue was linked to the amino groups of L-lysyl-L-lysine through spacer arms of three different lengths (C2, C4, and C9) to give trivalent beta-lactosyl clusters in order to increase the inhibitory activity of the beta-lactosyl group against tumor cell colonization. Thus, O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->4)-2,3, 6-tri-O-acetyl-glucopyranosyl trichloroacetimidate was treated with methyl or benzyl hydroxyethanoate, methyl or benzyl 4-hydroxybutanoate, and methyl 9-hydroxynonanoate, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate to give the corresponding beta-lactosides. These were coupled to L-lysyl-L-lysine, after conversion to the N-hydroxysuccinimide esters, to yield the corresponding trivalent beta-lactosyl-L-lysyl-L-lysine conjugates in good yields. The beta-lactosyl group with a C4 spacer arm was also coupled similarly to poly(L-lysine) (M(r) 3800) to form a polyvalent beta-lactosyl cluster. Coinjection of the trivalent (with C2 and C4 spacer arms) and polyvalent beta-lactosyl clusters with the highly metastatic B16 murine melanoma cells inhibited the formation of lung colonies in C57/BL mice, whereas the trivalent cluster with a C9 spacer arm displayed no activity.

Animals↗

PubMed1993

Introduction of hip ultrasonography to the neonatal services of a Fife District General Hospital.

Ultrasonography of the hip is a new technique which is said to assist in the diagnosis of neonatal hip disorders. The authors were unaware of any reports of formal evaluation of the introduction of this new technology into a District General Hospital. This study outlines several aspects of patient care before and after the introduction of neonatal hip ultrasonography to a Fife hospital as an adjunct to a neonatal orthopaedic clinic. After introduction of ultrasound the proportion of patients where the consultant was 'very confident' in the diagnosis increased by 29% (95% confidence intervals 9% to 49%); the proportion of children requiring three or more x-rays in the year following referral fell by 46% (95% confidence intervals 27% to 65%) and the proportion of children requiring five or more follow up attendances in the year following referral fell by 56% (95% confidence intervals 38% to 74%). Introduction of this technology has benefited patients by reducing their need to attend clinics and reducing their overall exposure to ionising radiation. There is a continuing need for ultrasonography to be provided in Fife neonatal orthopaedic outpatient clinics.

Data Collection↗

PubMed1993

Effect of weekend physical therapy treatment on postoperative length of stay following total hip and total knee arthroplasty.

Postoperative length of stay (LOS) may be affected by more intensive physical therapy following surgery. This study was designed to assess whether LOS could be affected by weekend physical therapy following surgery in patients who had undergone total hip arthroplasty (THA) or total knee arthroplasty (TKA). Weekend coverage for these patients was made possible by increased staffing in the Physical Therapy Department. The study group consisted of 84 patients who had undergone THA or TKA and had physical therapy treatment the weekend following surgery. The Control group consisted of 53 patients who had undergone THA or TKA prior to the implementation of the weekend intervention program. A retrospective chart audit was used to obtain pertinent information about control group patients. In the total sample mean LOS following weekend therapy (10.84 days) was significantly different (p < 0.05) from mean LOS prior to implementation of the study (12.28 days). Significant decreases in postoperative LOS were also found within the two subgroups of patients who had undergone THA and TKA. The results indicate that physical therapy treatment the weekend following THA or TKA significantly decreases postoperative LOS when physical therapy resources are increased to accommodate this increase in coverage.

Adolescent↗

PubMed1992

Identification of a dopamine-binding protein on the membrane of the human platelet.

The binding of [3H]dopamine to platelet membranes has been examined in an attempt to identify the putative dopamine-uptake mechanism of the platelet. [3H]Dopamine has been shown to bind to a 42,000 Da glycoprotein in platelet membrane with high affinity (Kd = 22.6 nM) and binding of [3H]dopamine was competed for by dopamine, molecules with catechol moieties, 5-hydroxytryptamine, GSH and ascorbic acid. Differences in pharmacological profile and molecular mass suggest that [3H]dopamine does not bind to a known receptor, a neuronal-type dopamine transporter or the platelet 5-hydroxytryptamine-uptake site. It is proposed that this novel binding site for dopamine, which has been purified 1000-fold from particulate platelet membrane, is likely to be a component of the dopamine-uptake mechanism of the human platelet.

Biological Transport↗

PubMed1992

An assay to measure the simultaneous uptake of [3H]dopamine and [14C]serotonin by the human platelet reveals an imipramine-insensitive [3H]dopamine uptake mechanism.

To determine whether a specific dopamine uptake mechanism is present on the human platelet the simultaneous uptake of [3H]dopamine and [14C]serotonin by platelets was measured. Utilising a dual radiolabel uptake technique, platelets have been shown to take up serotonin more rapidly and to a greater extent than they take up dopamine. Furthermore, at high concentrations serotonin was able to reduce dopamine uptake by platelets by 60% whereas dopamine had no effect on serotonin uptake. Similarly, imipramine and reserpine reduced (97% and 74% respectively) serotonin uptake by platelets in a dose-dependent manner, but did not affect the uptake of dopamine. Our data show that platelets take up dopamine by a mechanism independent of the imipramine-sensitive serotonin uptake mechanism. Furthermore, the increased capacity of platelets to store serotonin is because serotonin, unlike dopamine, is transported into the dense granules of the platelet.

Biological Transport↗

PubMed1992

Dopamine uptake by platelets from subjects with schizophrenia: a correlation with the delusional state of the patient.

The uptake of 3H-dopamine by platelets from patients with a number of psychiatric disorders has been compared with that by platelets from normal volunteers. Overall, 3H-dopamine uptake by platelet-rich plasma (PRP) from 25 schizophrenic subjects did not differ from 3H-dopamine uptake by PRP from 22 nonschizophrenic patients and 61 normal volunteers. In the schizophrenic group, however, there was an increased spread of results with seven values falling outside the range of results observed in the control group. Furthermore, of the patients rated, only for the schizophrenic patients was there an inverse correlation between 3H-dopamine uptake by platelets and the rating for delusions on the Scale for the Assessment of Positive Symptoms. Thus, 3H-dopamine uptake by platelet seems, in some way, to be linked to be delusional state of the patient. Further study of 3H-dopamine uptake by platelets is warranted in a larger and more diverse group of patients to determine the significance of altered dopamine uptake by platelets from some schizophrenic subjects and the correlation between platelet 3H-dopamine uptake and the delusional state of these subjects.

Adult↗

PubMed1992

Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.

Adolescent↗

PubMed1991

Inhibition of [3H]dopamine uptake by platelets by the dopamine-D2 receptor agonist RU 24926.

We have examined the effect of the dopamine-D2 receptor agonist RU 24926 (N-n-propyl-di-beta(3-hydroxy-phenyl)-ethylamine HCl) on [3H]dopamine uptake by human platelets. RU 24926 reduced the uptake of [3H]dopamine by platelet-rich plasma and this affect was not reversed by the dopamine-D2 receptor antagonist haloperidol, or the dopamine-D1 receptor antagonist SCH 23390 (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol). These data suggest that RU 24926 reduces [3H]dopamine uptake by platelets by competing for the dopamine uptake mechanism on the platelet and not by activation of the dopamine-D2 receptor.

Benzazepines↗

PubMed1990

A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells.

Our previous study suggested that N,N-dimethylsphingosine, but not unsubstituted sphingosine, could be a modulator of protein kinase C in epidermoid carcinoma A431 cells, since N,N-dimethyl-D-erythrosphingenine showed a stronger stereospecific effect on protein kinase C activity in comparison with N,N-dimethyl-L-erythrosphingenine, unsubstituted D- or L-erythrosphingenine, and gangliosides (Igarashi, Y., Hakomori, S., Toyokuni, T., Dean, B., Fujita, S., Sugimoto, M., Ogawa, T., El-Ghendy, K., and Racker, E. (1989) Biochemistry 28, 6796-6800). Other studies also indicated that commercial sphingosine preparation has an enhancing effect on epidermal growth factor (EGF) receptor kinase activity in A431 cells (Davis, R. J., Girones, N., and Faucher, M. F. (1988) J. Biol. Chem. 263, 5373-5379; Faucher, M. F., Girones, N., Hannun, Y. A., Bell, R. M., and Davis, R. J. (1988) J. Biol. Chem. 263, 5319-5327). In the present paper, we report (i) the effect of N,N-dimethylsphingosine as compared with lyso-glycosphingolipids and other sphingolipid breakdown products on EGF receptor autophosphorylation and (ii) demonstration of endogenous N,N-dimethylsphingosine synthesis and the virtual absence of unsubstituted sphingosine in A431 cells. The autophosphorylation of EGF receptor in the absence of detergent was strongly enhanced by N,N-dimethyl-D-erythrosphingenine; this effect was even obvious in the absence of EGF and synergistic in the presence of EGF. Similar enhancing activity was not produced by N,N-dimethyl-L-erythrosphingenine, D- and L-erythrosphingenine, N-monomethyl-D-erythrosphingenine, N-acetyl-D-erythrosphingenine, or the five lyso-glycosphingolipids tested. Labeling of sphingosine in A431 cells by culturing in medium containing [3H]Ser for various durations, followed by extraction and isolation of sphingolipids by standard procedures, resulted in clear bands corresponding to N,N-dimethylsphingosine and ceramide, whereas the band corresponding to sphingosine was virtually absent. The bands corresponding to N,N-dimethylsphingosine and ceramide intensified when cells were treated with metabolic inhibitor for UDP-Glc:Cer beta-Glc transferase (which causes accumulation of ceramide). These results indicate that N,N-dimethylsphingosine acts as a stereospecific enhancer for EGF receptor kinase and is able to produce EGF-like activity in vitro even in the absence of EGF and detergent. Under physiological conditions, N,N-dimethylsphingosine is the major catabolite resulting from ceramide breakdown.

Carcinoma, Squamous Cell↗

PubMed1990

Validation of a method to measure the uptake of [3H]dopamine by human platelets.

We have assessed the validity of using platelet-rich plasma (PRP) to measure dopamine uptake by platelets. In addition, we report on a pilot study comparing [3H]dopamine uptake by PRP from psychotic patients to that by PRP from healthy volunteers. Uptake of radiolabelled dopamine by PRP was related to the concentration of [3H]dopamine added and correlated with platelet number. [3H]dopamine uptake by PRP was not altered by varying pH (6.8 to 8.0) or by the time PRP was incubated prior to the addition of the radiolabelled dopamine. 11.7 +/- 0.34% (mean +/- SEM) of [3H]dopamine added to plasma was precipitated by polyethylene glycol (PEG) and appeared to be associated with a large molecular mass component of plasma. The amount of PEG precipitable [3H]dopamine did not correlate with dopamine uptake (r = 0.02) or differ between patients and controls. Uptake of [3H]dopamine by PRP from 52 volunteers (26 M, 26 F; age, 18-75 yr), expressed as the area under the dopamine uptake curve up to 60 min in arbitrary units, ranged from 72-285 for males and 59-455 for females. Comparing [3H]dopamine uptake by PRP from 15 psychotic patients to these sex-specific reference ranges 9 of 13 PRP from schizophrenic patients had [3H]dopamine uptake outside the normative values whereas the two non-schizophrenic patients did not differ from normal. Dopamine uptake by PRP may be useful in the study of diseases with altered dopaminergic activity in the CNS.

Adolescent↗

PubMed1990

Evidence for post-translational processing of auriculin B to atriopeptin III immediately prior to secretion by hypothalamic neurons in culture.

In rats, the precursor of atrial natriuretic peptide (ANP) is produced and processed into its smaller congeners in the heart and the brain. We have demonstrated that a congener of ANP, auriculin B (ANP4-28), was present in long term monolayer cultures of neonatal rat hypothalamic neurons. In addition, forskolin and 3-isobutyl-1-methyl-xanthine (IBMX) augmented the cellular content of auriculin B in a dose dependent manner. Thus, cyclic AMP may act as an intracellular signal for modulating the functional development of hypothalamic immunoreactive (ir) ANP producing neurons. Furthermore, our data suggest that the form of ANP released from these cultures, following either forskolin treatment alone or forskolin treatment followed by acute high potassium depolarisation, was atriopeptin III (ANP5-28). Thus atriopeptin III, rather than auriculin B, may represent the endogenous ligand for ANP receptors in the central nervous system.

1-Methyl-3-isobutylxanthine↗

PubMed1990

Effect of lactose derivatives on metastatic potential of B16 melanoma cells.

The effects of various sugars and sugar derivatives on lung colonization (i.e., metastatic deposition) of the highly metastatic BL6 clone of B16 mouse melanoma cells in syngeneic mice were studied, based on the assumption that carbohydrate structures, particularly those with a Gal terminus, play a crucial role in defining the metastatic potential of B16 cells. After incubation with sugar compounds (usually at 0.1 M concentration), tumor cells were injected via the tail vein into 8-week old female mice. Mice were sacrificed after 18-21 days, and tumor cell colonies in lung were counted under a dissecting microscope. Only methyl beta-D-lactoside and lacto-N-tetraose caused significant reduction (35-45% and 36%, respectively) of metastatic deposition compared to controls. Methyl beta-D-lactoside did not exhibit a growth inhibitory effect on BL6 tumor cells, as determined by several methods: in vitro [3H]thymidine incorporation assay, in vitro plating in RPMI-1640 medium culture under physiological conditions followed by cell counting, and in vivo subcutaneous inoculation of age-matched C57/BL mice followed by tumor measurement. These results indicate that the inhibitory effect of methyl beta-D-lactoside on tumor deposition was not related to its effect on tumor cell growth.

Animals↗

PubMed1990

Treated vs reported toxic exposures: discrepancies between a poison control center and a member hospital.

Statistics accumulated by Poison Control Centers (PCC) are routinely used on the local, regional and national levels by governmental agencies to set policy and direct funding. Incomplete reporting by member hospitals is recognized by PCC as a factor contributing to discrepancies in epidemiological estimates; however little emphasis is classically placed by the PCC on expanding reporting from member hospitals. A 1y retrospective review of patients with toxic exposure presenting to an urban Emergency Medicine Department (EMD) was performed to quantify the lack of concordance between treated and reported toxic exposures. 470 toxic exposures presented over the study period, of which only 123 (26%) were relayed to the regional PCC. Inhalation exposures were least likely to be referred for PCC consultation (3%); whereas PCC consultation was obtained for 33% venomous snake bite cases, and 95% of the cyclic antidepressant ingestions. Clusters of similar exposures resulted in fewer PCC consultations. Understanding each hospital's "profile" for handling toxic exposures, and individualized advertisement by the PCC to their member hospital may increase their data reporting. The statistical significance of their epidemiological studies as well as their revenue may increase.

Environmental Exposure↗

PubMed1989

Dopamine uptake by the human platelet: effects of dopamine receptor agonists.

The uptake of dopamine by human platelets has been shown to be temperature- and energy-dependent and not to occur as a result of dopamine binding to and then being internalised with the dopamine D-1 or D-2 receptor. However, occupancy of these receptors could affect dopamine uptake by platelets through their second messenger systems. We have therefore studied the effect of dopamine receptor agonists, which stimulate receptor second messenger systems, on dopamine uptake by platelets. Uptake of [3H]dopamine by human platelets was not affected by the dopamine D-1 receptor agonist SKF 38393 or the dopamine D-2 receptor agonists, quinpirole and bromocriptine. In contrast, the uptake of [3H]dopamine was decreased by the mixed dopamine receptor agonists dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN). Furthermore, [3H]ADTN, like [3H]dopamine, was taken up by platelets. In conclusion ADTN, a compound structurally similar to dopamine appears to complete for the dopamine uptake system on the human platelet. Thus, our data further support the hypothesis that a selective dopamine uptake system is present on the human platelet and that this system is not influenced by the dopamine D-1 or D-2 receptor.

Blood Platelets↗

PubMed1989

Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities.

In view of the possible effects of the sphingoid base on protein kinases, and the fact that the sphingoid bases used in previous studies were not chemically well-defined, we have studied the effects of chemically well-defined sphingosines and their derivatives on kinase activity. Both (4E)-D- and (4E)-L-erythro-sphingenine showed a weak inhibitory effect, and (4E)-L-threo-sphingenine had a moderate inhibitory effect. In contrast, (4E)-N,N-dimethyl-D-erythro-sphingenine and the sphingosine preparation from a commercial source showed a strong inhibitory effect on PK-C in A431 cells as well as on purified PK-C. Synthetic (4E)-D-erythro-sphingenine and several samples of natural sphingosine inhibited v-src or c-src tyrosine kinase activity measured with polyglutamate-tyrosine (4:1) as substrate. N-Acetylated or N-methylated sphingosines did not inhibit src kinase activity, but rather produced a consistent 1.5-2-fold stimulation of such activity.

Animals↗

PubMed1989

Specific interaction between Lex and Lex determinants. A possible basis for cell recognition in preimplantation embryos and in embryonal carcinoma cells.

The Lex determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc-beta 1----R) has been implicated as having a role in mediating compaction of the mouse embryo at the morula stage (Fenderson, B., Zehavi, U., and Hakomori, S. (1984) J. Exp. Med. 160, 1591-1596). Here, we present evidence suggesting a role for Lex in F9 embryonal carcinoma cell adhesion and a mechanism for Lex recognition based on carbohydrate-carbohydrate interaction. Homotypic aggregation of F9 cells was inhibited by lacto-N-fucopentaose III, and F9 cells showed a preferential interaction with Lex liposomes. The following observations suggest that the structure capable of recognizing Lex per se on F9 cells is Lex: (i) Cell surface-labeled components solubilized in octylglucoside, affinity-bound on an Lex-octyl-Sepharose column, contained glycoproteins reactive with anti-Lex antibody. (ii) Liposomes containing Lex showed significant interaction with Lex glycolipid, but not other glycolipids, coated on a plastic surface. (iii) Liposomes containing Lex glycolipid were found to self-aggregate, whereas liposomes containing paragloboside (nLc4) or sialylparagloboside (IV3NeuAcnLc4) did not. (iv) The diffusibility of 3H-labeled lacto-N-fucopentaitol III (but not I or II), incubated with Lex liposome, from the lower to the upper Boyden chamber through a semipermeable membrane was inhibited. In all these experiments (i-iv), the interaction of Lex to Lex (or Lex to lacto-N-fucopentaose III) was clearly observed only in the presence of Ca2+ and Mg2+ and was enhanced by the presence of Mn2+. These interactions were inhibited by EDTA. The results suggest the novel hypothesis that carbohydrate-carbohydrate interactions may play an important role in controlling cell recognition during F9 cell aggregation and during embryonic development.

Animals↗