Biomedical subjects

K Ferguson

Publications and source records attributed to K Ferguson.

At least 37 records · Page 2Linked to original sources

PubMed1999

From novice to competent practitioner: tracking the progress of undergraduate mental health nursing students.

This study explores the perceptions of, and outcomes for, a group of undergraduate mental health nursing students over a 3-year period from the point at which they made their choice to take the mental health branch of a 4-year degree programme in nursing, to working in the practice setting as registered nurses. Semi-structured interviews were completed at three points in their career: (a) at the end of the common foundation programme, when students had made their choice to take the mental health option; (b) at the end of the fourth year of the undergraduate programme; and (c) 1 year post-qualification. Questions were generated around five main themes: career choice, personal change and development, evaluation of the curriculum, ideas about mental health nursing and career plans. Despite some initial ambivalence at the start of the branch, students were happy with their career choice at follow-up, which was reinforced by significant clinical progress. All of the group were working in acute hospital settings despite being in possession of the community mental health qualification. Substantial evidence of these students' 'fitness for purpose' is offered, although some disillusionment with the contrast between student life and the real world of work is noted. Questions are posed as to the role of clinical supervision and education in preventing negative professional socialization. Recommendations are also made about recruitment to and design of mental health nursing courses.

Career Choice↗

PubMed1999

Outcome of femoropopliteal angioplasty.

OBJECTIVE: To assess prospectively the outcome of femoropopliteal angioplasty and investigate prognostic indicators of success. BACKGROUND: Percutaneous transluminal angioplasty is commonly used to treat symptomatic femoropopliteal stenoses or occlusions, but the durability of the procedure is uncertain. METHODS: Seventy-four consecutive patients treated by femoropopliteal angioplasty for intermittent claudication (43), rest pain (4), and tissue loss (27) were followed by assessment of symptoms, ankle-brachial pressure index (ABPI) to measure hemodynamic outcome, and duplex monitoring of velocity gradient at the angioplasty site to identify restenosis at 1 day and 3, 6, 9, and 12 months. Univariate comparisons, life table analysis, and backward stepwise regression were used to investigate factors predicting the symptomatic and hemodynamic outcome and restenosis. RESULTS: Technical success was obtained in 67 patients (91%); failure occurred in 7 patients. At 1 year, a successful symptomatic outcome was achieved in 35 patients (51%), hemodynamic success was achieved in 41 patients (58%), and restenosis developed in 39%. ABPI at 24 hours after angioplasty was the most significant variable predicting a symptomatic outcome, hemodynamic outcome, and restenosis at 12 months. Life table analysis demonstrated that in 24% of patients with a 24-hour ABPI > or =0.9, restenosis developed by 12 months, compared with 64% of patients with a 24-hour ABPI <0.9. CONCLUSION: Only half of the patients treated by femoropopliteal angioplasty had symptomatic improvement at 1 year, raising concern about the cost-benefit ratio of this procedure. Restoration of ABPI to >0.9 predicted a favorable outcome.

Angioplasty, Balloon↗

PubMed1999

Evaluating the usefulness of computerized adaptive testing for medical in-course assessment.

PURPOSE: This study investigated the feasibility of converting an existing computer-administered, in-course internal medicine test to an adaptive format. METHOD: A 200-item internal medicine extended matching test was used for this research. Parameters were estimated with commercially available software with responses from 621 examinees. A specially developed simulation program was used to retrospectively estimate the efficiency of the computer-adaptive exam format. RESULTS: It was found that the average test length could be shortened by almost half with measurement precision approximately equal to that of the full 200-item paper-and-pencil test. However, computer-adaptive testing with this item bank provided little advantage for examinees at the upper end of the ability continuum. An examination of classical item statistics and IRT item statistics suggested that adding more difficult items might extend the advantage to this group of examinees. CONCLUSIONS: Medical item banks presently used for incourse assessment might be advantageously employed in adaptive testing. However, it is important to evaluate the match between the items and the measurement objective of the test before implementing this format.

Automation↗

PubMed1999

Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol.

BACKGROUND: Tardive dyskinesia is important in the side-effect profile of antipsychotic medication. AIMS: The development of tardive dyskinesia was evaluated in patients treated with double-blind, randomly assigned olanzapine or haloperidol for up to 2.6 years. METHODS: Tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS) and Research Diagnostic Criteria for Tardive Dyskinesia (RD-TD), it was defined as meeting RD-TD criteria at two consecutive assessments. The risk of tardive dyskinesia, the relative risk, incidence rate, and incidence rate ratio were estimated. RESULTS: The relative risk of tardive dyskinesia for the overall follow up period for haloperidol (n = 522) v. olanzapine (n = 1192) was 2.66 (95% CI = 1.50-4.70). Based on data following the initial six weeks of observation (during which patients underwent medication change and AIMS assessments as frequently as every three days), the one-year risk was 0.52% with olanzapine (n = 513) and 7.45% with haloperidol (n = 114). The relative risk throughout this follow-up period was 11.37 (95% CI = 2.21-58.60). CONCLUSION: Our results indicated a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol.

Antipsychotic Agents↗

PubMed1999

p27 cell-cycle inhibitor is inversely correlated with lymph node metastases in right-sided colon cancer.

p27, a cyclin-dependent kinase inhibitor, suppresses proliferation of normal and neoplastic cells. Expression of p27 is correlated with survival in colon cancer. To some degree, right-sided colon cancers differ biologically and clinically from left-sided colon cancers. We analyzed 41 patients with right-sided colon cancers, including 18 cases with regional lymph node metastases and 23 cases with negative lymph nodes. Immunostaining for p27 was performed on histologic sections of primary cancers and scored. Correlation of p27 protein expression with histologic parameters was performed by t-test and multivariate analysis. Decreased p27 protein expression was associated with large tumor size. As percentages of positively stained tumor cells decreased from 70 to 29%, the mean tumor size increased from 1.9 to 7.3 cm. p27 protein expression significantly decreased in primary cancers with angiolymphatic invasion or with positive lymph nodes in comparison with those without angiolymphatic invasion (26 +/- 6 vs. 44 +/- 5%, P < 0.03) or with negative lymph nodes (23 +/- 4 vs. 47 +/- 6%, P < 0.003). p27 expression was not statistically different in terms of depth of tumor invasion (T1/T2 vs. T3/T4), tumor type or tumor differentiation. Multivariate analysis revealed that low p27 expression in primary cancers was correlated with lymph node metastases (P = 0.01). However, it did not correlate with any other histologic parameters. In summary, decreased p27 expression was associated with an increased likelihood of lymph node metastases in colon cancers, independent of depth of tumor invasion. This implies that p27 is a potentially important predictor for tumor metastasis and patient's prognosis in right-sided colon cancers.

Adenocarcinoma↗

PubMed1999

Loss of TGFbeta, Apoptosis, and Bcl-2 in Erectile Dysfunction and Upregulation of p53 and HIF-1alpha in Diabetes-Associated Erectile Dysfunction.

Vasculogenic erectile dysfunction (ED) is associated with collagen replacement of the cavernosal smooth muscle, mediated by an increase in transforming growth factor (TGF)-production secondary to hypoxemia. We tested the hypothesis that human ED is the result of an increase in apoptosis of the cavernosal smooth muscle cells with replacement by collagen, mediated by the TGFbeta upregulation. We also examined the tissue for proteins associated with apoptosis. Human cavernosal tissue was procured from impotent men at the time of prosthesis insertion. Normal corpous cavernosum served as a control. The TUNEL assay was used to assess apoptosis. Immunohistochemistry staining was used to detect TGFbeta and Bcl-2 expression, while Western blot analysis was used to detect expression of Bcl-2, p53, and hypoxia-inducible factor (HIF)-1a. Immunohistochemistry showed downregulation of TGFbeta protein expression in the corpus cavernosum of men with ED. Apoptotic nuclei were noted in cavernosal smooth muscle from a potent man but were not found in cavernosal tissue from men with ED. To gain insight into the possible mechanism of apoptosis in men with ED, the proto-oncogene Bcl-2, a potential inhibitor of apoptosis, was examined. Both immunohistochemistry and Western analysis revealed the presence of Bcl-2 in the cavernosal nerve of a potent man but its absence in cavernosal tissue from men with ED. Thus, loss of Bcl-2 expression correlated with the loss of apoptosis. In contrast, Western blotting demonstrated upregulation of p53 and HIF-1a expression in the cavernosal tissues from the men with ED and diabetes. Male ED follows an active process characterized by a loss of TGFb expression, apoptosis, and Bcl-2 expression. However, there is upregulation of p53 and HIF-1a in men with diabetes. These data support the possibility of hypoxia-mediated ED in diabetes via upregulation of p53 and HIF-1a but does not substantiate a role for TGFbeta in ED.

Journal Article↗

PubMed1998

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.

Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence assembled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100012 Da (PDE5A1). Extracts prepared from yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was inhibited by the selective PDE5 inhibitors zaprinast and DMPPO. PDE5A mRNA is expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protein with eight unique amino acids at the amino terminus. PDE5A maps to chromosome 4q 25-27.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

Analysis of multiplexed short tandem repeat (STR) systems using capillary array electrophoresis.

The profiling of polymorphic short tandem repeat (STR) markers is being applied to human identification, parentage testing and genetic mapping. Reliable genotyping of these markers is facilitated by polymerase chain reaction (PCR) amplification and high-resolution electrophoretic separation. Capillary array electrophoresis (CAE) offers very rapid, high-resolution separation of the amplified DNA and potential for automated sample processing not realized employing conventional slab-gel electrophoresis. The use of CAE to type DNA samples amplified at 11 genetic loci in multiplex profiles is presented. Two sets totaling 208 samples were amplified in a multiplex fashion using AmpFlSTR-Blue or AmpFlSTR-Green I and analyzed in a blind study using CAE. With the exception of one sample, the CAE genotyping results were in complete agreement with results obtained using a single-capillary system or two slab-gel electrophoresis systems. The sample, genotype TH01 7/10, migrated similar to TH01 6.3/9.3 allele sizes, which suggested a potential band migration shift. The recommended approach to such an observation is to analyze the sample again. The sample was rerun and correct genotype verified. Allelic ladder samples were analyzed multiple times by CAE to determine sizing accuracy and precision. The sizing of over 240 allelic ladder samples yielded an average within-run precision of +/- 0.13 bp and between-run precision of +/- 0.21 bp for fragments up to 350 bp. The CAE protocols permit processing of up to 96 multiplex STR samples in under 70 min.

Alleles↗

PubMed1998

Critical reexamination of palynological characters used to delimit Asclepiadaceae in comparison to the molecular phylogeny obtained from plastid matK sequences.

The family Asclepiadaceae (Dicotyledones) was created by Brown in 1810 by splitting in two the family Apocynaceae of Jussieu established in 1789. The morphological characters used to make this distinction were mainly palynological, such as presence of tetrads or pollinia and number and orientation of pollinia. Those characters, still used in higher taxonomic delimitation (families, subfamilies, and tribes), are here critically reexamined and compared to a molecular phylogeny obtained with one of the more variable plastid genes (matK) of 46 species in the order Gentianales. In this molecular phylogeny, Asclepiadaceae form a monophyletic group derived from within Apocynaceae. Each of the subfamilies of Asclepiadaceae is monophyletic and based on reliable palynological characters, but palynological characters are not useful to delimit tribes of the subfamily Asclepiadoideae. Based on the molecular data, these tribes have undergone parallelisms in several reproductive traits.

Base Sequence↗

PubMed1998

Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase.

OBJECTIVES: To evaluate whether alterations in nitric oxide (NO) synthesis or activity contribute to age-related erectile dysfunction and to elucidate the mechanisms causing these alterations using the rabbit as our model of aging. METHODS: We compared the ability of the rabbit cavernosal smooth muscle to relax in the organ bath in response to acetylcholine (Ach, endothelium-dependent vasodilator), sodium nitroprusside (SNP, an NO donor), and A23187 (a calcium ionophore) in young (6 month old) and aged (2.5 to 3.5 year old) rabbits. In addition, the immunohistochemical expression of endothelial nitric oxide synthase (eNOS) in both young and aged rabbit cavernosal tissue was examined. Endothelial integrity was examined immunohistochemically with JC70. RESULTS: Ach-mediated relaxation of penile corporal tissue was significantly attenuated from a maximum of 68.39 +/- 6.27 (0.1 mM Ach, n = 4) in young rabbits to 39.02 +/- 4.88 (0.1 mM Ach, n = 6) in aged rabbits (P < 0.04). No statistically significant difference (P > 0.05) was noted between cavernosal relaxation to sodium nitroprusside between young rabbits (97.8%, 0.1 mM SNP, n = 5) and aged rabbits (76.1%, 0.1 mM SNP, n = 5). This suggested that the defect in the Ach-NO pathway was at the level of NO synthesis, not activity. Immunohistochemical staining for eNOS demonstrated upregulation in both the vascular endothelium and corporal smooth muscle of aged rabbit tissue compared with young rabbit cavernosal tissue (n = 5). Anatomic endothelial integrity was demonstrated in the young and aged rabbits by the presence of JC70. This suggested that the defect in the Ach-NO synthetic pathway was not at the level of eNOS and was not due to anatomic endothelial cell disruption. Finally, Ach-mediated cavernosal smooth muscle relaxation in the young rabbit was not significantly augmented (P > 0.05) in the presence of the calcium ionophore A23187 (10 microM). A23187, however, significantly augmented (P < 0.04) Ach-mediated relaxation in the aged rabbit from a maximum of 33.93 +/- 6.58 to 41.55 +/- 6.58 (10 microM Ach, n = 5). This suggested that a potential defect in the Ach-NO synthetic pathway was at the level of intracellular calcium flux and possibly at the level of the calcium-eNOS interaction. CONCLUSIONS: Endothelium-dependent relaxation is attenuated in the aging rabbit; eNOS is upregulated in the aging rabbit; and no difference is noted in response to direct NO donation between the young and aged rabbit. The endothelium is anatomically intact in both the young and aging rabbit. The calcium ionophore A23187 augmented the attenuated vasorelaxation in the aging rabbit cavernosum (although not to the levels seen in the young rabbit cavernosum) and had no effect on the young rabbit cavernosum. These data suggest that erectile dysfunction in the aging rabbit cavernosum appears to be related to endothelial dysfunction and is characterized by eNOS upregulation and aberrant intracellular calcium fluxes.

Acetylcholine↗

PubMed1998

A generalizability study of a new standardized rating form used to evaluate students' clinical clerkship performances.

PURPOSE: To investigate the measurement characteristics of standardized clinical evaluation forms (CEFs) used to assign grades for clerkship performance. METHOD: In 1996-97, the authors reviewed 5,168 CEFs completed for 175 students in eight clerkships. Limiting their analysis to the three clerkships that produced the most CEFs, the authors conducted a generalizability study to determine the five variance components for each clerkship. A decision study then calculated the generalizability coefficients and standard errors of measurement in each clerkship for varied numbers of raters and CEF items. RESULTS: The generalizability study found large variance components attributable to rater and rating context. The decision study found that, when three or more raters completed CEFs for a student, the generalizability coefficient and standard error of measurement reached levels acceptable for grading. Increasing the number of items on the CEF had no significant effect. CONCLUSION: The reliability of assigning students clerkship grades based on single CEFs is unacceptably low. However, CEFs can accurately measure students' clerkship performances if completed by three or more raters.

Clinical Clerkship↗

PubMed1998

The decision to lose weight.

The purpose of this article is to describe the reasons people give for deciding to lose weight compared by weight history and gender. The sample consisted of 162 Caucasian community volunteers. Data were obtained from an extensive open-ended interview that was analyzed using content analysis. Respondents were categorized into five groups, according to their success at weight loss: Successful, Always Normal Weight, Underweight, Clinically Successful, and Always Obese. The Clinically Successful and Always Obese were included in the category Unsuccessful Dieter. Reasons given for entering a weight-loss regime included attractiveness or appearance, health, fear, self-esteem issues, age, and competition. For the Successful Dieter, attractiveness and health were the two major motivations. Men and women were similar in their reasons for entering a weight-loss program. The issue of what makes a decision of sufficient importance to maintain weight loss remains unexplained. "Centrality" is offered as a possible explanation.

Adult↗

PubMed1997

Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase.

Human cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2A3) cDNAs were cloned from hippocampus and fetal brain cDNA libraries. A 4.2-kb composite DNA sequence constructed from overlapping cDNA clones encodes a 941 amino acid protein with a predicted molecular mass of 105,715 Da. Extracts prepared from yeast expressing the human PDE2A3 hydrolyzed both cyclic AMP (cAMP) and cyclic GMP (cGMP). This activity was inhibited by EHNA, a selective PDE2 inhibitor, and was stimulated three-fold by cGMP. Human PDE2A is expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas. The human PDE2A3 differs from the bovine PDE2A1 and rat PDE2A2 proteins at the amino terminus but its amino-terminal sequence is identical to the bovine PDE2A3 sequence. The different amino termini probably arise from alternative exon splicing of the PDE2A mRNA.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1997

Team-based versus preceptor-based assignment of junior surgery students.

BACKGROUND: Clinical evaluations of junior surgery students frequently lack sufficient detail for effective formative or summative feedback. We hypothesized that this was in part due to a lack of personal accountability associated with large general surgery teams, and that altering the format to assign students to specific surgical faculty preceptors rather than to teams would affect the clinical evaluation products. METHODS: Over a 1-year period, 154 junior medical students grouped into 8 successive clerkships were assigned alternately in the usual Team (3-5 junior students, with 2-4 general surgery faculty, 2-4 residents, and 0-2 senior students) or a new Preceptor format (1-2 students to each faculty preceptor). In order to keep the ratio of students to faculty low, approximately one-third of the Preceptor format students were assigned to subspecialists. RESULTS: The preceptor format resulted in the use of more adjectives to describe students in the open-ended portions of the faculties' clinical evaluations (mean of 3.2 as compared with 2.5, P = 0.003), and a greater proportion of students recommended for overall clinical Honors (47% as compared with 25%, P = 0.004). The clerkship format had no impact on exam performance, students' perceptions of the faculty, or the amount of students' self-reported clinical activity. Nevertheless, twice as many Team format students felt they had too few patients, whereas twice as many Preceptor students felt their informal instruction had been less than "good." CONCLUSIONS: Preceptor assignment increased the number of students recommended for Honors, but this did not correlate with students' exam performance. From the students' standpoint, each format had advantages and disadvantages. Limiting the number of students on the general surgery teams and adding structured formative feedback from faculty before the end of the clerkship might give students the instructional advantages of the Preceptor format without sacrificing those of the Team format.

Adult↗

PubMed1997

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

Adult↗

PubMed1997

Identification and characterisation of a human calmodulin-stimulated phosphodiesterase PDE1B1.

A cDNA encoding a calmodulin-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE) was isolated from a human brain cDNA library. The cDNA, designated HSPDE1B1, encoded a protein of 536 amino acids that shared 96% sequence identity with the bovine "63 kDa" calmodulin-stimulated PDE. The recombinant protein had cyclic nucleotide phosphodiesterase activity that was stimulated approximately 2-fold by Ca2+/calmodulin and preferred cGMP as substrate. In addition, the enzymatic activity of HSPDE1B1 was inhibited by phosphodiesterase inhibitors with potencies similar to that displayed toward the bovine PDE1 enzymes: IBMX approximately equal to 8-methoxymethyl-IBMX > vinpocetine approximately equal to zaprinast > cilostamide > rolipram. HSPDE1B1 mRNA was found predominantly in the brain. Lower mRNA levels were found in heart and skeletal muscle. In situ hybridisation of brain revealed expression of HSPDE1B1 predominately in neuronal cells of the cerebellum, hippocampus and caudate. The HSPDE1B1 gene was mapped to human chromosome 12. A partial genomic sequence of HSPDE1B1 was isolated and shown to contain two splice junctions that are conserved in the rat PDE4 and the Drosophila dunce genes.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1997

Regional distribution of the anticonvulsant and behavioural effects of bicuculline injected into the pontine reticular formation of rats.

Previous experimental work has established that activation of sites in the dorsal midbrain can suppress tonic hindlimb extension in the electroshock model of epilepsy. The most sensitive region for this effect is centred on the intercollicular area and is referred to as the dorsal midbrain anticonvulsant zone (DMAZ). Subsequent experiments have shown that the ipsilateral descending projection from this region to the ventrolateral pons is critically involved in mediating its tonic seizure-suppressing properties. The purpose of the present investigation was to test whether direct anticonvulsant effects in the electroshock model could be obtained from selective manipulation of DMAZ target regions in the ventrolateral pons. Animals were prepared with chronically implanted guide cannulae through which microinjections could be made directly into the lateral pontine reticular formation. Animals received injections of saline or bicuculline (25-100 pmol) administered either bilaterally or unilaterally. The effects of these injections on the animals' behaviour were determined in an open arena, after which maximal electroshock (1 s, 40 mA, 50 Hz AC) was administered via ear-clip electrodes and the duration of tonic hindlimb extension was recorded. Bilateral injections of bicuculline (100 pmol) suppressed tonic seizures at a significantly higher proportion of sites centred on DMAZ target regions of the ventrolateral pons than surrounding areas. For injections centred on this region the suppressive effects of bicuculline were dose-related in the range 25-100 pmol. Unilateral injections of bicuculline into the ventrolateral pons also effectively suppressed tonic seizures in the electroshock model. Within the ventral pons there was a significant association between the behavioural and anticonvulsant effects of bicuculline; injections suppressing tonic seizures were associated with the induction of fast continuous locomotor activity. These data confirm that the DMAZ recipient region of the ventrolateral pontine reticular formation is part of a circuit which can suppress the manifestation of tonic hindlimb extension in the electroshock model. Whether this property is related to the participation of this region in normal locomotion and posture remains to be determined.

Animals↗

PubMed1996

A novel HLA class II-independent TCR-mediated T cell activation mechanism is distinguished by the V beta specificity of the proliferating oligoclones and their capacity to generate interleukin-2.

Superantigens can induce proliferative T cell responses after complex formation with major histocompatibility complex (MHC) class II antigens. In this study, highly purified variant T cells from a histocompatibility leukocyte antigen (HLA) (human major histocompatibility complex) class II-deficient patient were stimulated with toxic shock syndrome toxin 1 (TSST-1) in the presence of either HLA class II-negative or normal antigen-presenting cells (APC). The proliferative responses were similar to those of normal T cells even when HLA class II structures were absent on both responding T cells and costimulatory APC. However, the V beta specificity of responding T cells differed depending on the presence or absence of HLA class II antigens on the APC. In the presence of HLA class II-negative costimulatory APC, TSST-1 induced primarily proliferation of V beta 2-expressing T cells, whereas in the presence of normal APC virtually all responding T cells expressed V beta elements different from V beta 2. In addition, in the presence of normal APC, T cells responding to TSST-1 produced much higher amounts of interleukin-2 than T cells proliferating in the presence of HLA class II-negative APC. These findings suggest that T cells bearing selected V beta elements can directly interact with and respond to superantigen without involvement of HLA class II structures. Thus, our findings introduce a novel and distinct T cell receptor-mediated activation mechanism by which specific subpopulations of T cells respond to superantigen in the absence of HLA class II structures on APC.

Antigen-Presenting Cells↗