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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 55 records · Page 3Linked to original sources
PubMed2002

In vitro transformation of human congenital naevus to malignant melanoma.

The incidence of melanoma is estimated to be growing at the second fastest rate among all cancers in the United States. The progression of the melanocyte to a malignant melanoma involves various sequential steps: development of benign naevocellular naevus, preneoplastic dysplastic naevus, primary melanoma, and metastatic melanoma. Despite these clearly defined stages, very little is known about the molecular events leading to melanoma progression. We established a human congenital naevus cell line (UISO-CMN-1). UISO-CMN-1 cells were confirmed to have melanocytic origin by S100 immunoreactivity and the presence of melanin granules and melanosomes. UISO-CMN-1 cells, even though they showed structural and numerical abnormalities in karyotype, were non-tumorigenic when transplanted into athymic mice. However, following frequent exposure to ultraviolet C radiation, UISO-CMN-1 cells acquired tumorigenic potential. Transformation of UISO-CMN-1 cells into tumorigenic cells was accompanied by induction of ganglioside-2 expression without any significant changes in cellular ganglioside-3. These transformed and non-transformed UISO-CMN-1 cell lines can serve as excellent research tools for studying the molecular changes associated with melanoma development and progression, and for identifying agents that might prevent development of malignant melanoma.

Animals↗
PubMed2002

Loss of p16 expression is associated with histological features of melanoma invasion.

While mutations of CDKN2A are associated with melanoma predisposition, the precise role of its gene product p16 in the development of sporadic melanoma is less clearly understood. We sought to determine the prevalence of p16 expression using immunohistochemical analysis in a population-based sample of melanoma tumours, and also to identify histological, phenotypic and environmental factors associated with the presence or absence of p16 expression. We conducted face-to-face interviews with 108 patients newly diagnosed with melanoma to ascertain their history of sun exposure, and recorded various phenotypic parameters. Paraffin sections of tumours from these patients were stained with an anti-p16 monoclonal antibody following antigen retrieval. Overall, 52 (48%) tumours expressed p16; nodular melanomas had significantly lower levels of p16 immunoreactivity than superficial spreading melanomas (P = 0.015). While no association was found between p16 expression and host phenotype, loss of p16 staining was associated with thicker lesions (p = 0.084) and a high mitotic index (P = 0.013). Taken together, these findings are consistent with loss of p16 being a late event in the progression of sporadic primary melanomas, being associated with tumours of a more aggressive nature.

Aged↗
PubMed2002

Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease.

BACKGROUND AND AIMS: Recent studies on appendicectomy rates in ulcerative colitis and Crohn's disease have generally not addressed the effect of appendicectomy on disease characteristics. The aims of this study were to compare appendicectomy rates in Australian inflammatory bowel disease patients and matched controls, and to evaluate the effect of prior appendicectomy on disease characteristics. METHODS: Patients were ascertained from the Brisbane Inflammatory Bowel Disease database. Controls matched for age and sex were randomly selected from the Australian Twin Registry. Disease characteristics included age at diagnosis, disease site, need for immunosuppression, and intestinal resection. RESULTS: The study confirmed the significant negative association between appendicectomy and ulcerative colitis (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.14-0.38; p<0.0001) and found a similar result for Crohn's disease once the bias of appendicectomy at diagnosis was addressed (OR 0.34, 95% CI 0.23-0.51; p<0.0001). Prior appendicectomy delayed age of presentation for both diseases and was statistically significant for Crohn's disease (p=0.02). In ulcerative colitis, patients with prior appendicectomy had clinically milder disease with reduced requirement for immunosuppression (OR 0.15, 95% CI 0.02-1.15; p=0.04) and proctocolectomy (p=0.02). CONCLUSIONS: Compared with patients without prior appendicectomy, appendicectomy before diagnosis delays disease onset in ulcerative colitis and Crohn's disease and gives rise to a milder disease phenotype in ulcerative colitis.

Adult↗
PubMed2002

Quantitative determination of plasma phenylalanine and tyrosine by electrospray ionization tandem mass spectrometry.

BACKGROUND: Phenylketonuria patients on protein-restricted diets require monitoring of their blood phenylalanine concentrations. Small sample volumes are essential for neonates and infants, with the need for results to be generated in a timely manner by robust methods. We present a tandem mass spectrometry assay for phenylalanine (and tyrosine) which fulfils these criteria. METHODS: Plasma samples were deproteinized using a methanolic solution of phenylalanine-d5 and tyrosine-d4 that served as the internal standards for the assay. Following centrifugation each liquid phase was dried in a well of a microtitre plate and the amino acids converted to butyl esters using butanolic hydrogen chloride. After drying again and reconstituting in 80% acetonitrile in water, the samples were analysed using electrospray ionization tandem mass spectrometry. RESULTS: For both phenylalanine and tyrosine the limit of detection was 1 micromol/L and the carry-over less than 1%. The assay was linear to 3000 micromol/L in both amino acids (phenylalanine: r= 0.999; tyrosine: r= 0.992). Inter-sample precision varied with concentration but was 3.4-5.2% for phenylalanine and 4.3-7.6% for tyrosine. Between-batch precision was more variable, being 4.1-12.9% for phenylalanine and 8.4%-10.5% for tyrosine. CONCLUSIONS: Good agreement was found between the assay and results from existing ion-exchange chromatography and high performance liquid chromatographic assays in this department. Carry-over and precision were acceptable for monitoring work and the linearity allowed most specimens to be analysed without dilution. Where available, tandem mass spectrometry offers a convenient means of transferring the routine work for both neonatal screening and monitoring to one instrument.

Humans↗
PubMed2001

Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.

In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.

Analysis of Variance↗
PubMed2001

Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families.

Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagic telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2. Other distinct phenotype-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995. All living patients and their first-degree relatives were invited to attend a detailed clinical examination and blood was drawn for mutation analysis. In two families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutation no individuals with PAVM were identified and only one patient had a history of severe GI bleeding. No mutations in the endoglin locus were found in either family.

Activin Receptors↗
PubMed2001

A pilot study comparing intratumoral oxygenation using the comet assay following 2.5% and 5% carbogen and 100% oxygen.

PURPOSE: Tumor hypoxia has been purported to be an important biologic factor in the failure of radical radiotherapy to achieve local control in many tumor types. This study was designed to evaluate the effect of breathing high oxygen content gas mixtures (oxygen with 0%, 2.5%, or 5% carbon dioxide) on tumor oxygenation measured using the Eppendorf polarographic oxygen electrode and the comet assay in accessible, hypoxic human tumors. METHODS AND MATERIALS: Using Eppendorf pO2 histography to identify hypoxic tumors (median pO2 < or = 10 mmHg), eligible patients were systematically allocated either 100% oxygen (O2) or oxygen with 2.5% or 5% carbon dioxide (CO2). Tumors were treated with 6-10 Gy during which two fine needle aspirates (FNA) were obtained from different regions of the lesion, one at midway and the other at completion of the radiation exposure. Gas breathing was initiated 4 min before radiation was commenced. A 10-min interval was specified between the first and second halves of the radiation exposure to allow near maximal DNA repair prior to the second half of the radiation treatment. FNAs were performed within 2 min of cessation of radiation and the cells immediately suspended in buffered saline at 4 degrees C for analyses of hypoxic fraction using the comet assay. RESULTS: Fifteen evaluations were performed in 13 patients with hypoxic tumors (median O2 tension 2.75 mmHg) treated with a median dose of 8 Gy. The median hypoxic fraction determined using the comet assay fell from 0.36 to 0.13 (p = 0.001, Wilcoxon signed rank test) due to the addition of high oxygen content gases. CONCLUSIONS: In tumors defined as hypoxic using Eppendorf pO2 histography, a statistically significant reduction in the hypoxic fraction with the comet assay was found following administration of high oxygen content gases. These preliminary findings reveal a trend suggesting that 5% carbogen may reduce the hypoxic fraction by a greater margin than either 100% oxygen or 2.5% carbogen.

Analysis of Variance↗
PubMed2001

The microsomal epoxide hydrolase Tyr113His polymorphism: association with risk of ovarian cancer.

Functional significance has been demonstrated in vitro for the exon 3 T-->C Tyr113His amino acid substitution polymorphism of the microsomal epoxide hydrolase (EPHX) gene. The higher activity or fast TT genotype was previously reported to be associated with an increased risk of ovarian cancer, and this association may reflect enhanced activation of endogenous or exogenous substrates to more reactive and mutagenic derivatives. Components of cigarette smoke are examples of exogenous substrates subject to such bioactivation, and smoking exposure may thus modify the risk associated with the EPHX polymorphism. We examined 545 cases of epithelial ovarian cancer and 287 unaffected controls for this EPHX T-C genetic variant to investigate whether, in the Australian population, the TT genotype was associated with (i) specific ovarian tumor characteristics; (ii) risk of ovarian cancer, overall or for specific subgroups; and (iii) risk of ovarian cancer in smokers specifically. Genotyping was carried out using the Perkin-Elmer ABI Prism 7700 Sequence Detection System for fluorogenic polymerase chain reaction allelic discrimination. Stratification of the ovarian cancer cases according to tumor behavior (low malignant potential or invasive), grade, stage, and p53 immunohistochemical status failed to show any heterogeneity with respect to the genotype defined by the EPHX polymorphism. There was a suggestion of heterogeneity with respect to histologic subtype (P=0.03), largely due to a decreased frequency of the TT genotype in endometrioid tumors. EPHX genotype distribution did not differ significantly between unaffected controls and ovarian cancer cases (overall, low malignant potential, or invasive) either overall or after stratification by smoking status. However, the TT genotype was associated with a decreased risk of invasive ovarian cancer of the endometrioid subtype specifically (age-adjusted odds ratio=0.38, 95% confidence interval=0.17-0.87). The results suggest that the proposed EPHX-mediated bioactivation of components of cigarette smoke to mutagenic forms is unlikely to be involved in the etiology of ovarian cancer in general but that a greater rate of EPHX-mediated detoxification may decrease the risk of endometrioid ovarian cancer. Mol. Carcinog. 30:71-78, 2001.

Adult↗
PubMed2001

Residents' perceptions of water quality improvements following remediation work in the Pymme's Brook catchment, north London, UK.

Residents' perceptions of water quality change following remediation work in the upper Pymme's Brook catchment (north London) were elicited by questionnaire and compared with monitored changes in Escherichia coli count and BMWP (The Biological Monitoring Working Party (BMWP)) score. The wider usefulness of consumer perception surveys was then discussed. Monthly data collected between 1990 and 1996 shows that both E. coli count and BMWP score improved following flushing of the foul sewerage system in 1992, but that only E. coli count improved following the subsequent completion of large-scale remedial engineering works. Local residents were surveyed regarding their awareness of the scheme, and the causes of pollution, together with their perceptions as to the effects of the engineering works and of the resulting water quality improvements. Most respondents selected and ranked indicators in a way that suggested they had an awareness of the significance of various indicators of pollution severity. Following completion of the remediation scheme, residents perceived the watercourse to contain less rubbish and sewage fungus, and to have an improved colour and smell, which corresponds favourably to the monitored improvements. However, respondents' perceptions were found to vary when the study population was sub-divided using a range of parameters. For instance, frequent observers of the brook were most likely to correctly identify sewage as the main form of pollution. These divergent perceptions suggest that there may be considerable difficulties when perception surveys are used to quantify 'benefits' following environmental improvement programmes. Nevertheless, the survey was clearly beneficial in enhancing residents' awareness of their environment and the role of their voice in its management.

Adolescent↗
PubMed2001

Trends in the incidence of childhood-onset diabetes in Europe 1989-1998.

AIMS/HYPOTHESIS: To study the epidemiology of childhood-onset (Type I) insulin-dependent diabetes mellitus in Europe, the EURODIAB collaborative group in 1988 established prospective, geographically-defined registers of all children diagnosed with Type I diabetes under 15 years of age. This report is based on 24,423 children, registered by 36 centres, with complete participation during the period 1989-1998 and representing most European countries with a population coverage of approximately 20 million children. METHODS: Multiple sources of ascertainment were used to validate the level of ascertainment. Trends in Type I diabetes incidence during the period were analysed using Poisson regression with the results from the 36 centres pooled into nine regions. RESULTS: The standardised average annual incidence rate of Type I diabetes varied more than tenfold between centres. Overall, the annual increase in incidence was 3.2% (95%-CI: 2.7%, 3.7%), being highest for children in the 0-4-year age-group 4.8% (3.8%, 5.9%) and lowest for children in the 10-14-year age group 2.1 % (1.4%, 2.8%). However, the absolute increases in Type I diabetes were roughly similar in the three age-groups of 0-4, 5-9 and 10-14 years. Central Eastern Europe showed the highest increase whereas Sardinia and Northern Europe (except Finland) showed no evidence of an increase. For all age-groups relatively fewer cases had disease onset during the summer months, especially the 10-14-year age-group. CONCLUSION/INTERPRETATION: The extremely large range of incidence rates within Europe has been confirmed. The incidence rate is generally increasing but is more pronounced in some regions than in others. Seasonality at disease onset is apparent even in the youngest age-group.

Adolescent↗
PubMed2001

The large increase in incidence of Type I diabetes mellitus in Poland.

AIMS/HYPOTHESIS: A rising incidence of Type I (insulin-dependent) diabetes mellitus in different countries in Europe during the last decade has been recently reported. However, in the early 1990s, Poland was reported to have a stable low incidence of this disease. This study aimed to estimate the annual incidence of Type I diabetes in a north-eastern region of Poland (Białystok region) and investigate if it is associated with age, sex, urban rural differences and the season of disease onset. METHODS: A register of patients with Type I diabetes using two independent sets of data sources was established in 1994 as part of the EURODIAB TIGER programme. The primary data sources were paediatric and internal medicine divisions of the hospitals in the Białystok province and the secondary were outpatient diabetic clinics in the region. The degree of ascertainment was 98.5 % for the combinated data sources. RESULTS: We found a significant rising trend in the incidence of Type I diabetes in children under 15 years of age (in 1998 the incidence was approximately twice as high as in 1994). Increasing incidence rates were observed in the rural areas but not in urban populations. Seasonal variation in the incidence was also found, with a peak in winter and nadir in summer. CONCLUSIONS/INTERPRETATION: These results show that the north-eastern region of Poland is an area with a moderate rather than a low risk of Type I diabetes. Our observations confirm the important role of environmental and socio-economic factors or both in the pathogenesis of Type I diabetes.

Adolescent↗
PubMed2001

Correlations between the incidence of childhood-onset type I diabetes in Europe and HLA genotypes.

There are large variations in the incidence of Type I (insulin-dependent) diabetes mellitus within Europe, ranging from 3.2 cases per 100,000 person-years in the Republic of Macedonia to more than 40 new cases per 100,000 person-years in Finland. This variation could be caused by differences in the distribution of genetic susceptibility markers, by differences in the distribution of environmental disease determinants or by a combination of both. To assess how much genes contribute to this variation, we correlated the level of incidence of Type I diabetes with the prevalence in the general population of genetic susceptibility and protective markers encoded by the human leukocyte antigen (HLA)-DQ loci. Positive association was found for the combined group of genotypes associated with Type I diabetes risk (p < 0.001). The whole positive effect was, however, accounted for by the HLA-DQ2/ DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302) and HLA-DQ4/DQ8 (DQA1*0401-DQB1*0402/DQA*0301-DQB1*0302) genotypes (p < 0.001 and p < 0.004, respectively). No correlation was found between incidence of Type I diabetes and population prevalence of genotypes not encoding for aspartate on position 57 on the HLA-DQbeta chain. It was not possible to detect any negative correlation between Type I diabetes incidence and the prevalence of HLA-genotypes conferring protection against Type I diabetes in a population (HLA-DQA1*0102-DQB1*0602/X). The results suggest that a substantial part of the transnational variation in the incidence of childhood-onset Type I diabetes in Europe is explained by variations between populations in the distribution of particular DQ genotypes which confer a high risk of Type I diabetes in the general population.

Age of Onset↗
PubMed2001

Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study. European and Dibetes.

AIMS/HYPOTHESIS: We aimed to describe the frequency and degree of diabetic ketoacidosis in children across Europe at the time of diagnosis of Type I (insulin-dependent) diabetes mellitus and to determine if factors such as age and geographical region contribute to the risk of diabetic ketoacidosis. METHODS: The study was part of the EURODIAB project. A total of 24 centres, covering a population at risk of more than 15 million children below 15 years of age, recruited 1,260 children at the time of clinical diagnosis. RESULTS: Polyuria, by far the most frequent symptom, was observed in 96% of the children. In only 25% of the children was the duration of symptoms less than 2 weeks and this proportion was larger in the under 5 year age-group (37 vs 22%; p < 0. 001). Of the 11 centres that recorded diabetic ketoacidosis status, the overall proportion with diabetic ketoacidosis (pH < 7.3) was 40% (95%-CI: 36-44%) in at least 90 % of cases. After stratification by centre, the odds ratio for diabetic ketoacidosis in the under 5 age-group was 1.02 (95%-CI:0.69-1.49) relative to the older children. There was significant variation between the 11 centres in the frequency of diabetic ketoacidosis which ranged from 26 to 67% (p = 0.002). An inverse correlation between the frequency of diabetic ketoacidosis and the background incidence rate was found in these centres (Spearman's rank correlation, rs = -0.715;p = 0.012). CONCLUSION/INTERPRETATION: Rising standards of medical information and greater awareness concurrent with an overall increase in incidence could have resulted in changes in the clinical presentation at onset of Type I childhood diabetes in Europe.

Age Factors↗
PubMed2001

Is childhood-onset type I diabetes a wealth-related disease? An ecological analysis of European incidence rates.

AIMS/HYPOTHESIS: To describe the epidemiology of childhood-onset Type I (insulin-dependent) diabetes mellitus in Europe, the EURODIAB collaborative group established prospective, geographically-defined registers of children diagnosed under 15 years of age. A total of 16,362 cases were registered by 44 centres during the period 1989-1994. The registers cover a population of approximately 28 million children with most European countries represented. METHODS: In most centres a primary and a secondary source of ascertainment were used so that the completeness of registration could be assessed by the capture-recapture method. Ecological correlation and regression analyses were used to study the relationship between incidence and various environmental, health and economic indicators. RESULTS: The standardised average annual incidence rate during the period 1989-94 ranged from 3.2 cases per 100,000 person-years in the Former Yugoslavian Republic of Macedonia to 40.2 cases per 100,000 person-years in Finland. Indicators of national prosperity such as infant mortality (r = -0.64) and gross domestic product (r = 0.58) were most strongly and significantly correlated with incidence rate and previously-reported associations with milk consumption (r = 0.58), coffee consumption (r = 0.51) and latitude (r = 0.40) were also observed. CONCLUSION/INTERPRETATION: The wide variation in childhood Type I diabetes incidence rates within Europe could be partially explained by indicators of national prosperity. These indicators could reflect differences in environmental risk factors such as nutrition or lifestyle that are important in determining a country's incidence rate.

Adolescent↗
PubMed2001

Transgenic expression of a delta 12-epoxygenase gene in Arabidopsis seeds inhibits accumulation of linoleic acid.

The Crepis palaestina cDNA Cpal2 encodes a delta 12-epoxygenase that can catalyse the synthesis of 12,13-epoxy-cis-9-octadecenoic acid (18:1E) from linoleic acid (18:2). When the Cpal2 gene was expressed under the control of the napin seed-specific promoter in Arabidopsis thaliana (L.) Heynh., the seed lipids accumulated only low levels of 18:1E and also 12,13-epoxy-cis-9,15-octadec-2-enoic acid (18:2E). Despite the fact that the levels of these epoxy fatty acids comprised only up to 6.2% of the total fatty acids, there was a very marked increase in oleic acid (18:1) and decrease in linoleic (18:2) and alpha-linolenic (18:3) acids in these plants, indicating that endogenous delta 12-desaturation was greatly reduced in these plants. Significant between-line differences in the levels of Cpal2 mRNA were observed during seed development, but were not associated with any major variation in mRNA levels for the endogenous Arabidopsis delta 12-desaturase (Fad2). This suggests that if an unfavourable interaction occurs between the transgenic delta 12-epoxygenase and the endogenous delta 12-desaturase, which decreases the level of desaturation, it occurs at either the translational or post-translational level. We further show that the co-expression of a delta 12-desaturase gene from C. palaestina in Cpal2 transgenic Arabidopsis returns the relative proportions of the C18 seed fatty acids to normal levels and results in an almost twofold increase in total epoxy fatty acids.

2S Albumins, Plant↗
PubMed2001

Adenomyosis--a result of disordered stromal differentiation.

Adenomyosis is a fairly frequent disorder in adult women characterized by the haphazard location of endometrial glands and stroma deep within the myometrium of the uterus. This study compared the effects on uterine development of the selective estrogen receptor modulators, tamoxifen, toremifene, and raloxifene with estradiol when given orally to female mice on days 2 to 5 after birth. Uterine adenomyosis was found in all (14 of 14) mice dosed with tamoxifen and most mice (12 of 14) treated with toremifene, but in none of the vehicle-dosed controls, in only one animal treated with raloxifene at 42 and 90 days after dosing and in none of the mice treated with estradiol at 42 days. At 6 days, the uterus in the groups that developed a high incidence of adenomyosis showed histological evidence of disturbed differentiation of the myometrium. Gene-expression XY-scatterplots using Clontech mouse 1.2 Atlas mouse cDNA expression arrays analyzing total uterine RNA showed nerve growth factor-alpha, preadipocyte factor-1, and insulin-like growth factor-2 were key genes differentially modified by tamoxifen or toremifene treatment, relative to the controls. As these genes may play an important role in regulating differentiation and development of the myometrium, these data suggest that adenomyosis may be caused primarily by defects in the formation of the myometrium.

Administration, Oral↗
PubMed2001

Gabapentin is not a GABAB receptor agonist.

Recent experiments have demonstrated that formation of functional type B gamma-aminobutyric acid (GABA(B)) receptors requires co-expression of two receptor subunits, GABA(B1) and GABA(B2). Despite the identification of these subunits and a number of associated splice variants, there has been little convincing evidence of pharmacological diversity between GABA(B) receptors comprising different subunit combinations. However, Ng et al. [Mol. Pharmacol., 59 (2000) 144] have recently suggested a novel and important pharmacological difference between GABA(B) receptor heterodimers expressing the GABA(B1a) and GABA(B1b) receptor subunits. This study suggested that the antiepileptic GABA analogue gabapentin (Neurontin) is an agonist at GABA(B) receptors expressing the GABA(B1a) but not the GABA(B1b) receptor subunit. The importance of this finding with respect to identifying novel GABA(B) receptor subunit specific agonists prompted us to repeat these experiments in our own [35S]-GTPgammaS binding and second messenger assay systems. Here we report that gabapentin was completely inactive at recombinant GABA(B) heterodimers expressing either GABA(B1a) or GABA(B1b) receptor subunits in combination with GABA(B2) receptor subunits. In addition, in both CA1 and CA3 pyramidal neurones from rodent hippocampal slices we were unable to demonstrate any agonist-like effects of gabapentin at either pre- or post-synaptic GABA(B) receptors. In contrast, gabapentin activated a GABA(A) receptor mediated chloride conductance. Our data suggest that gabapentin is not a GABA(B)-receptor agonist let alone a GABA(B) receptor subunit selective agonist.

Acetates↗