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Biomedical subjects

Jonathan Green

Publications and source records attributed to Jonathan Green.

At least 19 recordsLinked to original sources
PubMed2006

HepSEQ: International Public Health Repository for Hepatitis B.

HepSEQ is a repository for an extensive library of public health and molecular data relating to hepatitis B virus (HBV) infection collected from international sources. It is hosted by the Centre for Infections, Health Protection Agency (HPA), England, United Kingdom. This repository has been developed as a web-enabled, quality-controlled database to act as a tool for surveillance, HBV case management and for research. The web front-end for the database system can be accessed from http://www.hpa-bioinfodatabases.org.uk/hepatitis_open/main.php. The format of the database system allows for comprehensive molecular, clinical and epidemiological data to be deposited into a functional database, to search and manipulate the stored data and to extract and visualize the information on epidemiological, virological, clinical, nucleotide sequence and mutational aspects of HBV infection through web front-end. Specific tools, built into the database, can be utilized to analyse deposited data and provide information on HBV genotype, identify mutations with known clinical significance (e.g. vaccine escape, precore and antiviral-resistant mutations) and carry out sequence homology searches against other deposited strains. Further mechanisms are also in place to allow specific tailored searches of the database to be undertaken.

Databases, Factual↗
PubMed2006

Characterisation of small double stranded RNA molecule in Cryptosporidium hominis, Cryptosporidium felis and Cryptosporidium meleagridis.

Coding regions of double stranded RNA molecules from 3 human faecal samples containing Cryptosporidium hominis, C. felis and C. meleagridis were characterised by sequencing and compared with that previously obtained for C. parvum. Sequences outside the coding regions were also obtained. Overall similarities of between 86% and 92% and between 86% and 93% were observed in the nucleotide and amino acid sequences respectively between these species. These larger sequences will allow further molecular tools for detection, identification and characterisation of Cryptosporidium spp.

Animals↗
PubMed2006

Dipeptide nitrile inhibitors of cathepsin K.

A series of dipeptidyl nitriles as inhibitors of cathepsin K have been explored starting from lead structure 1 (Cbz-Leu-NH-CH2-CN, IC50 = 39 nM). Attachment of non-natural amino acid side chains in P1 and modification of the P3 subunit led to inhibitors with higher potency and improved pharmacokinetic properties.

Animals↗
PubMed2006

Characterisation of norovirus strains in rural Ghanaian children with acute diarrhoea.

The incidence of calicivirus infection in Ghana and many other African countries is not known. Thirteen (15.9%) of the 82 diarrhoeic stool samples tested for caliciviruses were positive for noroviruses (NoVs). NoVs were present in all age groups and were detected only during the diarrhoea peak that coincided with the peak rotavirus season. Ten (76.9%) of the NoV detected were genogroup II (GII) NoVs and the remaining three (23.1%) genogroup I (GI) NoVs. The predominant GII detected was GII-4 (60%, 6/10). Three of the GII NoVs were determined to be recombinants of GII-8/GII-14 as deduced from the sequencing of the region spanning the Orf1/2 junction. The GII genotypes formed four clusters with published GII sequences. The data shown enhances understanding of NoV diversity in Ghanaian children and demonstrate the global spread of distinct common genotypes to African countries.

Acute Disease↗
PubMed2006

Annotation: the therapeutic alliance--a significant but neglected variable in child mental health treatment studies.

BACKGROUND: There has been relatively little research into therapeutic alliance in child and adolescent mental health and virtually no incorporation of alliance measures as a variable in treatment trials in Child and Adolescent Mental Health Services (CAMHS). METHOD: A selective literature review on studies in therapeutic alliance in adulthood and childhood along with a theoretical formulation of possible mechanisms of alliance. RESULTS: Therapeutic alliance is reliably measurable both by observation and questionnaire methods at all points in the treatment cycle. In both adult and child studies it shows a consistent, albeit modest, association with treatment outcome. In specific adult studies it has shown a high predictive validity in relation to outcome compared to other variables. In child studies alliance is particularly salient in externalising disorder and predicts outcome of inpatient treatment. Child alliance and parental alliance are independent factors. Theoretical models of alliance outlined in this paper suggest testable hypotheses regarding predictors for positive and negative alliance. CONCLUSIONS: Therapeutic alliance in CAMHS is measurable and worth measuring. It is likely to be an important variable for treatment outcome studies and should be included in future trial designs.

Adolescent↗
PubMed2004

Application of the heteroduplex mobility assay (HMA) for the investigation of the genomic diversity among noroviruses in environmental samples.

Recent studies have demonstrated the widespread contamination of river and seawater with noroviruses (NV), often with more than one strain. The heteroduplex mobility assay (HMA) in which amplicons from study samples are hybridised (by denaturing and reannealing) to amplicons from reference strains and resolved by electrophoresis, has the potential to provide a simple and rapid means to identify samples containing multiple NV strains and to establish the diversity of strains within that sample. PCR amplicons from environmental samples that were tested directly in the HMA assay were shown to contain more than one strain. In order to evaluate HMA for investigations of NV diversity in environmental samples, amplicons from three representative samples were cloned and, for each, 20 amplicons derived from individual clones were analysed by HMA. Between two and six different HMA profiles were demonstrated among clones from a single sample indicating the extent of NV diversity in the sample. Sequence analysis confirmed the relationship of HMA profile and NV 'genotype'. Far greater diversity was seen among Genogroup (G) II (Ni/E3) amplicons than Genogroup (G) I (Ando/E3) amplicons (generated from the RNA dependent RNA polymerase region of the ORF1 of noroviruses), which often contained only a single strain, which is reflective of the greater prevalence of GII NVs over GI NVs. Overall, four GII and four GI strains were identified in these environmental water/sewage samples.

Base Sequence↗
PubMed2004

Methods for the detection and characterisation of noroviruses associated with outbreaks of gastroenteritis: outbreaks occurring in the north-west of England during two norovirus seasons.

This article describes the methods used to investigate 407 outbreaks of acute non-bacterial gastroenteritis occurring in the North-West of England between January 2000 and July 2001 and suspected to be caused by noroviruses (NV) [Mayo (2002) Arch Virol 147:1655-1663]. These included 319 outbreaks in hospitals and nursing homes and 88 other settings. Eight hundred and seventy-one faecal samples from 407 outbreaks were tested using electron microscopy (EM), an enzyme-linked immunosorbent assay (ELISA) specific for Grimsby virus (GRV) capsid antigen and/or by reverse transcriptase-polymerase chain reaction (RT-PCR) for NV, allowing the utility of each assay for routine diagnosis to be assessed. Preliminary genomic characterisation of detected strains was performed using the heteroduplex mobility assay (HMA) and DNA sequencing. The results demonstrate the continuing predominance of GII-4 GRV strain of NV as a cause of outbreaks, particularly in hospital and nursing home settings. Overall, NV were detected in 223/407 (55%) of outbreaks tested. However, a wide range of apparently diverse strains was identified, including several not previously reported. Genomic characterisation revealed clusters of linked outbreaks not recognised previously.

Antigens, Viral↗
PubMed2004

The nitrogen-containing bisphosphonate, zoledronic acid, increases mineralisation of human bone-derived cells in vitro.

Previous studies have attributed the increase in bone mass observed following bisphophonate (BP) therapy to their effects on bone-resorbing osteoclasts (OCs). However, recent evidence suggests that BPs can also act directly on bone forming osteoblasts (OBs) to increase their anabolic activity. Using an established model of in vitro OB differentiation, we found that the potent nitrogen-containing BP, zoledronic acid (ZOL), may enhance the bone forming potential of human adult OB-like cells in vitro by inducing their differentiation. ZOL dose dependently induced both cytostasis and cell death in OB-like cells at concentrations of 0.5 microM or greater. Cells expressing high levels of the osteoprogenitor antigen, STRO-1, exhibited a greater proliferative potential than STRO-1negative/dim cells, and were more susceptible to the cytostatic and apoptotic effects of ZOL. ZOL was also found to promote bone cell differentiation, as evidenced by an increase in the number of cells exhibiting a more differentiated (STRO-1(-)/AP+ and STRO-1(-)/AP-) phenotype. Analysis of gene expression, using semi-quantitative RT-PCR, demonstrated that ZOL treatment resulted in a significant upregulation of osteocalcin (OCN) and bone morphogenetic protein-2 (BMP-2) gene expression. Furthermore, in vitro mineralisation studies revealed that ZOL enhanced mineralised matrix formation at concentrations between 5 and 25 microM. These results show that, in addition to its direct effects on OCs, ZOL also directly affects the proliferation and differentiation of human OB-like cells in vitro and may enhance bone formation in vivo.

Calcification, Physiologic↗
PubMed2004

A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness.

BACKGROUND: Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone. METHODS: The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments. RESULTS: All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain. CONCLUSIONS: A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.

Autistic Disorder↗
PubMed2004

Diversity of noroviruses cocirculating in the north of England from 1998 to 2001.

A study was undertaken to investigate the diversity of noroviruses (NVs) in fecal samples from patients from 529 outbreaks and 141 sporadic cases of gastroenteritis in the North of England from September 1998 to August 2001. NV strains were detected by electron microscopy and characterized by a combination of the Grimsby virus antigen enzyme-linked immunosorbent assay, reverse transcriptase PCR, the heteroduplex mobility assay, and DNA sequencing. Twenty-one distinct NV strains, including several novel or variant strains not seen previously, were found circulating in the population studied. Genogroup II NVs were responsible for 83% of the outbreaks. Several strains cocirculated at any one time. The Bristol (Grimsby/Lordsdale) and Hawaii (Girlington) genotypes were the most prevalent among the NVs identified, detected in 49 and 20% of the outbreaks, respectively. A limited number of other genogroup II and I strains were cocirculating. The virus populations detected in hospitals and nursing homes were distinct from those found in community-based outbreaks. Outbreaks in hospitals and nursing homes were more likely to be caused by genogroup II strain Grimsby or Girlington (P < 0.0001) than by other genogroup II or I strains.

Caliciviridae Infections↗
PubMed2004

The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE).

UNLABELLED: Bisphosphonates are used to prevent osteoclast-mediated bone loss. Zoledronic acid inhibits osteoclast maturation indirectly by increasing OPG protein secretion and decreasing transmembrane RANKL expression in human osteoblasts. The decreased transmembrane RANKL expression seems to be related to the upregulation of the RANKL sheddase, TACE. INTRODUCTION: Bisphosphonates (BPs) exhibit high affinity for hydroxyapatite mineral in bone and are used extensively to treat malignancy-associated bone disease and postmenopausal bone loss by inhibiting osteoclast (OC)-mediated bone resorption. MATERIALS AND METHODS: We examined the effect of the most potent nitrogen-containing BP available, zoledronic acid (ZOL), on the expression of RANKL and osteoprotegerin (OPG), critical factors in the regulation of OC formation and activation, in primary osteoblast (OB)-like cells derived from human bone, using flow cytometry, ELISA, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ immunofluorescence staining, and Western blotting. RESULTS: Our studies show that ZOL, while not significantly affecting RANKL or OPG gene expression, markedly increased OPG protein secretion and reduced transmembrane RANKL protein expression in OB-like cells. The reduction in transmembrane RANKL expression was preceded by a marked increase in the expression of the metalloprotease-disintegrin, TNF-alpha converting enzyme (TACE). In addition, the decreased transmembrane expression of RANKL could be partially reversed by a TACE inhibitor, TAPI-2. CONCLUSIONS: Our studies indicate that ZOL, in addition to its direct effects on mature OCs, may inhibit the recruitment and differentiation of OCs by cleavage of transmembrane RANKL in OB-like cells by upregulating the sheddase, TACE.

ADAM Proteins↗
PubMed2003

A rapid method for identifying diversity within PCR amplicons using a heteroduplex mobility assay and synthetic polynucleotides: application to characterisation of dsRNA elements associated with Cryptosporidium.

A 173-bp fragment of the small extra-chromosomal double-stranded RNA (dsRNA) element of Cryptosporidium parvum was generated by reverse transcriptase PCR from nucleic acid extracted from whole faeces of 18 epidemiologically unrelated cases of cryptosporidiosis. Eleven different sequences were detected and two selected as reference DNA in a heteroduplex mobility assay (HMA). Although sequence diversity was detected, this was difficult to characterise because of the similarity in electrophoretic mobility of the homo- and heteroduplex bands. A PCR method was devised to generate synthetic polynucleotides of greater sequence diversity for use in the HMA. The presence of the synthetic 173-bp fragments was enriched by using, as template for the PCR, material excised from the area of the heteroduplex bands in stained electrophoresis gels. Nine novel sequences were generated and evaluated as reference sequences in the HMA. One of these with 20 bp different from the original sequence was selected for use in the HMA for improved resolution of heteroduplex and homoduplex bands and number of patterns easily resolved (nine different patterns corresponding to different DNA sequences). This method may be useful for analysis of DNA where there is limited natural variation or little sequence variation is described.

Animals↗
PubMed2003

Effect of the combination of docetaxel, zoledronic acid, and a COX-2 inhibitor on the growth of human breast cancer cell lines.

Current trends in the treatment of human tumors are with drug combinations that result in improved responses as well as the ability to use less toxic concentrations of the drugs. Recent reports have shown that COX-2 inhibitors and taxanes are effective in the suppression of human tumor growth. The bisphosphonate, zoledronic acid, primarily used in the treatment of bone metastases, also inhibits proliferation and induces apoptosis in human breast and prostate carcinoma and multiple myeloma. HER-2/neu overexpression has been suggested as a mechanism for resistance to both hormonal therapy as well as chemotherapy. This study examines the effects of combining a cyclooxygenase-2 inhibitor with zoledronic acid and/or docetaxel in a HER-2/neu transfected and control human breast cancer cell line. All three compounds produced dose-dependent growth inhibition in both cell lines. The HER-2/neu transfected MCF/18 cells, however, were less sensitive to zoledronic acid than the control MCF/neo cells, 9% to 53% inhibition and 18% to 67%, respectively. Enhanced growth inhibition was observed in both cell lines with the combination of docetaxel and SC236 and the combination of docetaxel and zoledronic acid. The combination of SC236 with zoledronic acid also gave an enhanced inhibitory effect in the MCF/neo line. This combination, however, was additive in the HER-2/neu transfected MCF/18 cell line. The triple combination of SC236, zoledronic acid and/or docetaxel resulted in a small increase in growth inhibition compared to that seen with the double combinations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Molecular epidemiological analysis of Cryptosporidium isolates from humans and animals by using a heteroduplex mobility assay and nucleic acid sequencing based on a small double-stranded RNA element.

Two extrachromosomal double-stranded RNA (dsRNA) elements occur in Cryptosporidium parvum. A heteroduplex mobility assay (HMA) was developed for the rapid characterization of sequence diversity in a 173-bp fragment of the small dsRNA element of Cryptosporidium with either a natural sequence from Cryptosporidium meleagridis or a synthetic sequence as reference DNA. The 173-bp fragment was generated from 265 samples of whole feces (242 from humans and 18 from livestock with C. parvum genotype 1 or 2, 4 from humans with Cryptosporidium felis, and 1 from a human with C. meleagridis). The HMA method identified 21 patterns in C. parvum (8 in genotype 1, 12 in genotype 2, and a type common to both genotypes), 4 patterns in C. felis, and 1 pattern in C. meleagridis. All patterns were confirmed as distinct by DNA sequencing. For genotype 1, a single HMA type was found in 89% of samples: 64 of 65 cases from three waterborne outbreaks, all 16 cases from eight intrafamilial outbreaks, and 17 of 28 sporadic cases. Among the remaining 11 sporadic cases due to genotype 1, seven other HMA types were detected. For genotype 2, a single HMA type was found in 72% of samples: 36 of 43 cases from three waterborne outbreaks, 11 of 15 cases from seven intrafamilial outbreaks, 44 of 75 sporadic cases, and all 18 samples from livestock. Within the intrafamilial outbreaks, two other HMA types were identified: the same HMA type was detected in samples from cases within the same outbreak. Among the sporadic cases due to genotype 2, 10 additional HMA types were detected.

Animal Diseases↗