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C Allen

Publications and source records attributed to C Allen.

At least 127 records · Page 7Linked to original sources
PubMed1997

An exo-poly-alpha-D-galacturonosidase, PehB, is required for wild-type virulence of Ralstonia solanacearum.

Ralstonia solanacearum, which causes bacterial wilt disease of many plant species, produces several extracellular plant cell wall-degrading enzymes that are suspected virulence factors. These include a previously described endopolygalacturonase (PG), PehA, and two exo-PGs. A gene encoding one of the exo-PGs, pehB, was cloned from R. solanacearum K60. The DNA fragment specifying PehB contained a 2,103-bp open reading frame that encodes a protein of 74.2 kDa with a typical N-terminal signal sequence. The cloned pehB gene product cleaves polygalacturonic acid into digalacturonic acid units. The amino acid sequence of pehB resembles that of pehX, an exo-PG gene from Erwinia chrysanthemi, with 47.2% identity at the amino acid level. PehB also has limited similarity to plant exo-PGs from Zea mays and Arabidopsis thaliana. The chromosomal pehB genes in R. solanacearum wild-type strain K60 and in an endo-PG PehA- strain were replaced with an insertionally inactivated copy of pehB. The resulting mutants were deficient in the production of PehB and of both PehA and PehB, respectively. The pehB mutant was significantly less virulent than the wild-type strain in eggplant virulence assays using a soil inoculation method. However, the pehA mutant was even less virulent, and the pehA pehB double mutant was the least virulent of all. These results suggest that PehB is required for a wild-type level of virulence in R. solanacearum although its individual role in wilt disease development may be minor. Together with endo-PG PehA, however, PehB contributes substantially to the virulence of R. solanacearum.

Amino Acid Sequence↗
PubMed1997

Sharing care: the psychiatrist in the family physician's office.

OBJECTIVE: One way of strengthening ties between primary care providers and psychiatrists is for a psychiatrist to visit a primary care practice on a regular basis to see and discuss patients and to provide educational input and advice for family physicians. This paper reviews the experiences of a program in Hamilton, Ontario that brings psychiatrists and counsellors into the offices of 88 local family physicians in 36 practices. METHOD: Data are presented based on the activities of psychiatrists working in 13 practices over a 2-year period. Data were gathered from forms routinely completed by family physicians when making a referral and by psychiatrists whenever they saw a new case. An annual satisfaction questionnaire for all providers participating in the program was also used to gather information. RESULTS: Over a 2-year period, 1021 patients were seen in consultation by one full-time equivalent psychiatrist. The average duration of a consultation was 51 minutes, and a family member was present for 12% of the visits. Twenty-one percent of the patients were seen for at least one follow-up visit, 75% of which were prearranged. In addition, 1515 cases were discussed during these visits without the patient being seen. All participants had a high satisfaction rating for their involvement with the project. CONCLUSIONS: Benefits of this approach include increased accessibility to psychiatric consultation, enhanced continuity of care, support for family physicians, and improved communication between psychiatrists and family physicians. This model, which has great potential for innovative approaches to continuing education and resident placements, demands new skills of participating psychiatrists.

Consumer Behavior↗
PubMed1997

Long-term hyperglycemia is related to peripheral nerve changes at a diabetes duration of 4 years. The Wisconsin Diabetes Registry.

OBJECTIVE: To examine longitudinal hyperglycemia and peripheral nerve responses in a population-based incident cohort. RESEARCH DESIGN AND METHODS: A sample from an incident cohort of young people was comprehensively followed from diagnosis of IDDM. Participants were invited to submit blood samples three times per year for central testing of GHb. During their 4th year of diabetes, nerve conduction studies were performed on the median sensory and motor, peroneal motor, and sural sensory nerves. Relationships between mean GHb and nerve latencies, velocities, and amplitudes were explored. RESULTS: GHb was positively related to all nerve latencies and negatively related to all nerve velocities. The relationships between mean GHb and nerve conduction latencies and velocities differed by sex for the peroneal nerve latency (beta = 0.17 male subjects, beta = -0.01 female subjects; P < 0.001). Pubertal participants had lower velocities and longer latencies than prepubertal participants (beta = 0.37; P = 0.05 peroneal latency), after adjustment for GHb, height, and extremity temperature. Sensory and motor nerve amplitudes were related to GHb, and these relationships did not differ by sex. CONCLUSIONS: Our study indicates that sustained hyperglycemia is related to functional changes, at the minimum, in peripheral sensory and motor nerve conduction at a diabetes duration of 4 years. Our findings are consistent with a dying-back neuropathy, and there is some suggestion that chronic hyperglycemia may be more detrimental to nerves in male subjects than in female subjects.

Adolescent↗
PubMed1996

Longitudinal patterns of glycemic control and diabetes care from diagnosis in a population-based cohort with type 1 diabetes. The Wisconsin Diabetes Registry.

Glycosylated hemoglobin is an indicator of long-term glycemic control and a strong predictor of diabetic complications. This paper provides a comprehensive description of glycemic control (total glycosylated hemoglobin (GHb)) up to 4.5 years duration of diabetes by age, duration, and sex in a population-based cohort (n = 507) aged less than 20 years followed from diagnosis of Type 1 diabetes in Wisconsin during 1987-1994 Important aspects of demographics and diabetes care are described to allow comparison with other populations. Since large variations between laboratories are known to exist in the measurement of GHb, levels are also interpreted relative to the frequency of short-term complications. GHb increased after diagnosis, but leveled off after 2-3 years. Peak GHb values occurred in the age group 12-15 years. The within-individual standard deviation in GHb between tests, adjusted for age and duration was 1.6%. The mean GHb at last testing was 11.3%, with a standard deviation across individuals of 2.9%. The majority (74%) of individuals saw a diabetes specialist at least once. The mean number of insulin injections per day increased from 2.2 to 2.5 across the 4.5-year duration, and the insulin dose increased from 0.6 to 0.9 units per day per kg body weight. Despite the quite satisfactory level of care, 38% of subjects had GHb levels associated with significant short-term complications.

Adolescent↗
PubMed1996

Familial predisposition to neuroblastoma does not map to chromosome band 1p36.

Familial predisposition to neuroblastoma, a common embryonal cancer of childhood, segregates as an autosomal dominant trait with high penetrance. It is therefore likely that neuroblastoma susceptibility is due to germ line mutations in a tumor suppressor gene. Cytogenetic, functional, and molecular studies have implicated chromosome band 1p36 as the most likely region to contain a suppressor gene involved in sporadic neuroblastoma tumorigenesis. We now demonstrate that neuroblastoma predisposition does not map to any of eight polymorphic markers spanning 1p36 by linkage analysis in three families. In addition, there is no loss of heterozygosity at any of these markers in tumors from affected members of these kindreds. Furthermore, there is strong evidence against linkage to two Hirschsprung disease (a condition that can cosegregate with neuroblastoma) susceptibility genes, RET and EDNRB. We conclude that the neuroblastoma susceptibility gene is distinct from the 1p36 tumor suppressor and the currently identified Hirschsprung disease susceptibility genes.

Adolescent↗
PubMed1996

Cloning, chromosomal localization, physical mapping, and genomic characterization of HKR3.

The Krüppel-type zinc finger proteins are members of a conserved family of transcription factors that are important in developmental regulation. Altered expression of several of these proteins has been implicated in human diseases, including cancer. We report the cloning, mapping, and characterization of the zinc finger gene Human Krüppel-Related 3 (HKR3). Genomic clones of HKR3 were isolated from a P1 library and localized to human chromosome subband 1p36.3 by human-rodent somatic cell hybrid mapping and fluorescence in situ hybridization. The gene was physically mapped to within 40 kb of D1S214 by YAC content and long-range restriction mapping. HKR3 spans 9.5 kb of genomic DNA and is contained in 11 exons. Sequencing defined each of the exon/intron splice site junctions and identified a CpG island in the 5' region of the gene. HKR3 is ubiquitously expressed in human tissues as at least two major transcripts, the shorter of which excludes a conserved finger-associated box and a putative acidic activation domain contained in the full-length transcript. HKR3 is a novel zinc finger gene that maps to a region of the genome commonly rearranged or deleted in human cancers.

Adult↗
PubMed1996

Activation of corticostriatal pathway leads to similar morphological changes observed following haloperidol treatment.

Treatment with haloperidol, a dopamine receptor D-2 antagonist, for one month resulted in an increase in the mean percentage of asymmetric synapses containing a discontinuous, or perforated, postsynaptic density (PSD) [Meshul et al. (1994) Brain Res., 648:181-195] and a change in the density of striatal glutamate immunoreactivity within those presynaptic terminals [Meshul and Tan (1994) Synapse, 18:205-217]. We speculated that this haloperidol-induced change in glutamate density might be due to an activation of the corticostriatal pathway. To determine if activation of this pathway leads to similar morphological changes previously described following haloperidol treatment, GABA (10(-5) M, 0.5 microliters) was injected into the thalamic motor (VL/VM) nuclei daily for 3 weeks. This treatment resulted in an increase in the mean percentage of striatal asymmetric synapses containing a perforated PSD and an increase in the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated or non-perforated PSD. Subchronic injections of GABA into the thalamic somatosensory nuclei (VPM/VPL) had no effect on the mean percentage of synapses with perforated PSDs but resulted in a small, but significant, increase in density of glutamate immunoreactivity. Using in vivo microdialysis, an acute injection of GABA (10(-5) M, 15 microliters) into VL/VM resulted in a prolonged rise in the extracellular level of striatal glutamate. The increase in asymmetric synapses with perforated PSDs and in glutamate immunoreactivity within nerve terminals of the striatum following either subchronic haloperidol treatment or GABA injections into VL/VM suggest that an increase in glutamate release may be a common factor in these two experiments. It is possible that the extrapyramidal side effects associated with haloperidol treatment may be due, in part, to an increase in release of glutamate within the corticostriatal pathway.

Animals↗
PubMed1996

Correlation of vacuous chewing movements with morphological changes in rats following 1-year treatment with haloperidol.

Long-term treatment with the typical antipsychotic drug, haloperidol, can lead to a sometimes irreversible motor disorder, tardive dyskinesia (TD). It has been hypothesized that increased release of glutamate due to prolonged neuroleptic drug treatment may result in an excitotoxic lesion in specific neuronal populations within the basal ganglia, leading to TD. We reported that treatment with haloperidol for 1 month results in an increase in the mean percentage of striatal asymmetric synapses containing a perforated postsynaptic density (PSD) and that these synapses are glutamatergic. Using quantitative immunocytochemistry, we found that depending on how long the animals had been off haloperidol following subchronic (30 d) treatment, there was either a decrease (1 day off) or increase (3-4 days off) in the density of glutamate immunolabeling within the presynaptic terminals of synapses with perforated PSDs. Using a rat model for TD, animals in the current study were treated for 1 year with haloperidol and spontaneous oral dyskinesias (i.e. vacuous chewing movements, VCMs) were recorded. In these long-term treated animals we wanted to determine if there was a correlation between glutamate function, as measured by changes in synapses with perforated PSDs and the density of nerve terminal glutamate immunoreactivity, and VCM behavior. In drug treated rats which demonstrated either a high or low rate of VCMs, there was a significant increase in the mean percentage of asymmetric synapses in the dorsolateral striatum with perforated PSDs in both haloperidol-treated groups compared to vehicle-treated rats. There was a small but significant increase in the density of glutamate immunolabeling within striatal nerve terminals of the high VCM group compared to the low VCM group. There was, however, no difference in the density of glutamate immunolabeling between the high VCM group compared to the vehicle-treated animals. One reason for this lack of difference was partially due to a significant increase in nerve terminal area within the high VCM group compared to either the low VCM- or vehicle-treated groups. The larger nerve terminal size in the high VCM group may be due to a small but sustained increase in glutamate neurotransmitter release with the ability of the terminal to maintain its supply of glutamate, while the terminals in the low VCM group showed evidence of glutamate depletion. This finding would be consistent with the hypothesis that increased glutamatergic activity may be associated with TD.

Animals↗
PubMed1996

Immediate and delayed effects of laparoscopic Nissen fundoplication on pulmonary function.

BACKGROUND: An effort was made to assess the respiratory outcomes of laparoscopic Nissen fundoplication (LNF). METHODS: Prospective follow-up of 69 patients undergoing LNF for gastroesophageal reflux disease. Outcomes included pulmonary function testing, 24-h pH recording, esophageal manometry, and symptom assessment. RESULTS: There was an improvement (p < 0.0001) in heartburn and cough scores. There was a significant fall in spirometry (p < 0001), diffusing capacity (p < 0.0001), and respiratory muscle strength (p < 0.0001) 36 h after surgery, which had returned to baseline by 1 month. At 6 months, the patients (n = 16) with impaired preoperative diffusing capacity showed improvement (17.8 +/- 3.7 to 19.8 +/- 4.6 ml/min/mmHg, p = 0.0245). CONCLUSION: Patients undergoing LNF have impaired gas exchange before surgery which tends to improve 6 months after surgery. There is an early reversible impairment in respiratory function due to diaphragm dysfunction. Patients with a preoperative 1-s forced expired volume > 1.5, or 50% predicted, are unlikely to develop significant early respiratory complication.

Adult↗
PubMed1996

The effect of preoperative tranexamic acid on blood loss after cardiac operations in children.

Children undergoing cardiac operations in which cardiopulmonary bypass is used are at risk of significant postoperative blood loss. The acquired coagulopathy is complex but is thought to be due, in part, to excessive fibrinolysis. We examined the possibility of reducing postoperative blood loss in children by using the antifibrinolytic drug tranexamic acid. Using a prospective, randomized, double-blind study design, we administered a single dose of tranexamic acid (50 mg/kg intravenously) or saline placebo, before skin incision, in 88 children undergoing cardiac operations. Post-operative blood loss and fluid replacement were recorded for the next 24 hours. In addition, hemoglobin, platelet counts, and coagulation measures were recorded every 6 hours. When all patients were examined, there was no significant difference in postoperative blood loss between the treated and placebo groups (21.2 +/- 12 ml/kg per 24 hours, tranexamic acid, vs 27.2 +/- 20.3 mls/kg per 24 hours, placebo). However, when the children with cyanosis were analyzed separately, there was a highly significant difference in blood loss between the groups during the first 6 hours (11.2 +/- 3.7 ml/kg per 6 hours, tranexamic acid, vs 27.2 +/- 11.4 mls/kg per 6 hours, placebo; p < 0.002), as well as the overall 24 hour study period (23.7 +/- 7.5 mls/kg per 24 hours, tranexamic acid, vs 48.9 +/- 27.6 mls/kg per 24 hours, placebo; p < 0.02). Also significantly less blood and blood products were administered to the treated cyanosed group. Tranexamic acid produced a significant reduction in postoperative blood loss and blood product requirements in children with cyanosis undergoing heart operations. The drug had no effect in children without cyanosis or those requiring a second thoracotomy.

Adolescent↗
PubMed1996

Effects of subchronic clozapine and haloperidol on striatal glutamatergic synapses.

Subchronic treatment with haloperidol increases the number of asymmetric glutamate synapses associated with a perforated postsynaptic density in the striatum. To characterize these synaptic changes further, the effects of subchronic (28 days) administration of an atypical antipsychotic, clozapine (30 mg/kg, s.c.), or a typical antipsychotic, haloperidol (0.5 mg/kg, s.c.), on the binding of [3H] MK-801 to the NMDA receptor-linked ion channel complex and on the in situ hybridization of riboprobes for NMDAR2A and 2B subunits and splice variants of the NMDAR1 subunit were examined in striatal preparations from rats. The density of striatal glutamate immunogold labeling associated with nerve terminals of all asymmetric synapses and the immunoreactivity of those asymmetric synapses associated with a perforated postsynaptic density were also examined by electron microscopy. Subchronic neuroleptic administration had no effect on [3H] MK-801 binding to striatal membrane preparations. Both drugs increased glutamate immunogold labeling in nerve terminals of all asymmetric synapses, but only haloperidol increased the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated postsynaptic density. Whereas subchronic administration of clozapine, but not haloperidol, resulted in a significant increase in the hybridization of a riboprobe that labels all splice variants of the NMDAR1 subunit, both drugs significantly decreased the abundance of NMDAR1 subunit mRNA containing a 63-base insert. Neither drug altered mRNA for the 2A subunit, but clozapine significantly increased hybridization of a probe for the 2B subunit. The data suggest that some neuroleptic effects may be mediated by glutamatergic systems and that typical and atypical antipsychotics can have varying effects on the density of glutamate in presynaptic terminals and on the expression of specific NMDA receptor splice variant mRNAs. Alternatively, NMDAR1 subunit splice variants may differentially respond to interactions with glutamate.

Alternative Splicing↗
PubMed1996

Transient immunosuppression by FK506 permits a sustained high-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscles of adult dystrophic (mdx) mice.

Adenovirus (AV)-mediated gene transfer into skeletal muscles of adult immune-competent animals has been limited by the fact that a cell-mediated immune attack of the host against transduced muscle fibers prevented efficient long-term transgene expression. More recently, various immunomodulating strategies have been shown to improve the longevity of transgene expression after AV-mediated gene transfer. In this study we treated adult dystrophic (mdx) mice with daily subcutaneous injections of the immunosuppressive drug FK506 (tacrolimus) over 5, 10, 30 and 60 days after AV-mediated dystrophin gene transfer and compared the transduction level with saline-injected mdx controls. We show that daily FK506 treatment after AV-mediated dystrophin gene transfer into adult mdx muscle results in the maintenance of the initial transgene expression for at least 2 months, even when FK506 treatment was discontinued after 1 month. This is in keeping with the marked reduction of inflammatory infiltrates and the reduced activation level (inducible nitric oxide synthase) of macrophages in adenoviral recombinant (AVR)-injected muscles of FK506-treated animals. Moreover, we find that FK506 efficiently suppresses the humoral immune response against both the vector proteins and the transgene protein product (dystrophin). Furthermore, we demonstrate that continuous FK506 treatment over 30 days significantly improves the efficiency of gene transfer when the same vector is readministered to an animal which had been transduced 20 days earlier. In conclusion, the data suggest that sensitization by the initial antigenic load of the AVR application plays a pivotal role in triggering the humoral and cellular immune response of the host, which can be significantly counteracted by relatively short-term immunosuppressive treatment. These findings have important implications for the design of future human trials for gene replacement therapy in Duchenne muscular dystrophy.

Adenoviridae↗
PubMed1995

An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy.

The CD34 antigen is expressed by committed and uncommitted hematopoietic progenitor cells and is increasingly used to assess stem cell content of peripheral blood progenitor cell (PBPC) collections. Quantitative CD34 expression in PBPC collections has been suggested to correlate with engraftment kinetics of PBPCs infused after myeloablative therapy. We analyzed the engraftment kinetics as a function of CD34 content in 692 patients treated with high-dose chemotherapy (HDC). Patients had PBPCs collected after cyclophosphamide based mobilization chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF) until > or = 2.5 x 10(6) CD34+ cells/kg were harvested. Measurement of the CD34 content of PBPC collections was performed daily by a central reference laboratory using a single technique of CD34 analysis. Forty-five patients required a second mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg and 15 patients with less than 2.5 x 10(6) CD34+ cells/kg available for infusion received HDC. A median of 9.94 x 10(6) CD34+ cells/kg (range, 0.5 to 112.6 x 10(6) CD34+ cells/kg) contained in the PBPC collections was subsequently infused into patients after the administration of HDC. Engraftment was rapid with patients requiring a median of 9 days (range, 5 to 38 days) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 9 days (range, 4 to 53+ days) to achieve a platelet count of > or = 20 x 10(9)/L. A clear dose-response relationship was evident between the number of CD34+ cells per kilogram infused between the number of CD34+ cells per kilogram infused and neutrophil and platelet engraftment kinetics. Factors potentially influencing the engraftment kinetics of neutrophil and platelet recovery were examined using a Cox regression model. The single most powerful mediator of both platelet (P = .0001) and neutrophil (P = .0001) recovery was the CD34 content of the PBPC product. Administration of a post-PBPC infusion myeloid growth factor was also highly correlated with neutrophil recovery (P = .0001). Patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin had more rapid platelet recovery than patients receiving other regimens (P = .006), and patients requiring 2 mobilization procedures versus 1 mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg experienced slower platelet recovery (P = .005). Although a minimal threshold CD34 dose could not be defined, > or = 5.0 x 10(6) CD34+ cells/kg appears to be optimal for ensuring rapid neutrophil and platelet recovery.

Adolescent↗
PubMed1995

Immunosuppression by FK506 markedly prolongs expression of adenovirus-delivered transgene in skeletal muscles of adult dystrophic [mdx] mice.

Adenovirus-mediated gene transfer into skeletal muscles of adult immune competent animals has been limited by the fact that a cellular immune attack of the host against transduced muscle fibers prevented long-term transgene expression. In this study we treated adult dystrophic [mdx] mice with daily subcutaneous injections of the immunosuppressive drug FK506 (tacrolimus) over 10 and 30 days after adenovirus-mediated reporter gene transfer and compared the transduction level to saline-injected controls. After 30 days, transgene expression was no longer demonstrable in the control group, whereas it remained at about 70% of the 10-day transduction value in the FK506 treated group. In addition, we demonstrated a reduction in the number of CD3 and CD8 positive T-lymphocytes in the muscles of the immunosuppressed group compared to controls.

Adenoviridae↗
PubMed1995

A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3.

Deletion of the short arm of human chromosome 1 is the most common cytogenetic abnormality observed in neuroblastoma. To characterize the region of consistent deletion, we performed loss of heterozygosity (LOH) studies on 122 neuroblastoma tumor samples with 30 distal chromosome 1p polymorphisms. LOH was detected in 32 of the 122 tumors (26%). A single region of LOH, marked distally by D1Z2 and proximally by D1S228, was detected in all tumors demonstrating loss. Also, cells from a patient with a constitutional deletion of 1p36, and from a neuroblastoma cell line with a small 1p36 deletion, were analyzed by fluorescence in situ hybridization. Cells from both sources had interstitial deletions of 1p36.2-36.3 which overlapped the consensus region of LOH defined by the tumors. Interstitial deletion in the constitutional case was confirmed by allelic loss studies using the panel of polymorphic markers. Four proposed candidate genes--DAN, ID3 (heir-1), CDC2L1 (p58), and TNFR2--were shown to lie outside of the consensus region of allelic loss, as defined by the above deletions. These results more precisely define the location of a neuroblastoma suppressor gene within 1p36.2-36.3, eliminating 33 centimorgans of proximal 1p36 from consideration. Furthermore, a consensus region of loss, which excludes the four leading candidate genes, was found in all tumors with 1p36 LOH.

Base Sequence↗
PubMed1995

Laparoscopic Nissen fundoplication is a satisfactory alternative to long-term omeprazole therapy.

A total of 168 patients with proven gastro-oesophageal reflux disease (GORD) receiving long-term medical therapy underwent laparoscopic Nissen fundoplication. The operation was converted to open fundoplication in four patients. All patients reported complete (92.3 per cent) or partial (7.7 per cent) relief of reflux symptoms 1 month after surgery. There were no associated deaths and the perioperative complication rate was 8.9 per cent. The mean(s.e.m.) length of operating time was 69.9(2.4) min and mean(s.e.m.) hospital stay 2.7(0.1) days. Symptom score assessment, 24-h oesophageal pH recording and lower oesophageal sphincter pressure showed significant (P < 0.0001) improvement 6 months after surgery in 85 evaluable patients. Before operation 37.5 per cent of the patients were considered symptomatically controlled on omeprazole and had excellent symptom control after surgery. This initial experience suggests that laparoscopic Nissen fundoplication is a safe and effective treatment for patients with GORD requiring long-term medication.

Adolescent↗
PubMed1995

GM1 ganglioside administration partially counteracts the morphological changes associated with haloperidol treatment within the dorsal striatum of the rat.

Haloperidol, a typical antipsychotic drug, causes an increase in the mean percentage of synapses within the situation containing a discontinuous, or perforated, postsynaptic density (PSD) following 1 month of treatment (Meshul et al. 1994). This effect is not observed with the atypical antipsychotic drug, clozapine, following subchronic administration (Meshul et al. 1992a). This morphological change is also associated with an increase in the density of dopamine D2 receptors. The synapses containing the perforated PSD are asymmetrical and the nerve terminals contain the neurotransmitter, glutamate, as demonstrated by immunocytochemistry. We have also shown that subchronic treatment with haloperidol (0.5 mg/kg per day, 30 days) results in a decrease in the density of glutamate immunoreactivity within asymmetric nerve terminals associated with perforated and non-perforated PSDs (Meshul and Tan 1994). This could be due to an increase in glutamate release, perhaps due to activation of corticostriatal synapses. Agnati et el. (1983a) reported that administration of GM1 ganglioside blocks the increase in dopamine D2 receptors following haloperidol treatment. GM1 has also been shown to attenuate the release of glutamate (Nicoletti et al. 1989). In order to determine if similar treatment with ganglioside could block the haloperidol-induced ultrastructural changes notes above, rats were co-administered GM1 (10 mg/kg per day) and haloperidol (0.5 mg/kg per day) for 30 days. We report that GM1 blocked the haloperidol-induced increase in striatal asymmetric synapses containing a perforated PSD, but had no effect on the increase in dopamine D2 receptors or the decrease in nerve terminal glutamate immunoreactivity. GM1, either alone or co-administered with haloperidol, also caused a small, but significant, increase in the density of all asymmetric synapses within the striatum. It is possible that the effect of GM1 in attenuating the haloperidol-induced change in glutamate synapses with perforated PSDs is primarily postsynaptic, since GM1 did not block the change in density of glutamate immunoreactivity within asymmetric nerve terminals.

Animals↗