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Biomedical subjects

C M Jones

Publications and source records attributed to C M Jones.

At least 19 recordsLinked to original sources
PubMed2001

LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1.

LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a protein of 121 kDa. LIP1 appears to be a cytoplasmically located protein whereas we and others have shown previously that LKB1 is predominantly nuclear, with only a small proportion of cells showing strong cytoplasmic expression. However, when LKB1 and LIP1 are co-expressed, the proportion of cytoplasmic LKB1 dramatically increases, suggesting that LIP1 may regulate LKB1 function by controlling its subcellular localization. Ectopic expression of both LKB1 and LIP1 in Xenopus embryos induces a secondary body axis, providing further evidence for a functional link between the two proteins. This phenotype resembles the effects of ectopic expression of TGFbeta superfamily members and their downstream effectors. A possible role for LIP1 and LKB1 in TGFbeta signalling is supported by the observation that LIP1 interacts with the TGFbeta-regulated transcription factor SMAD4, forming a LKB1-LIP1-SMAD4 ternary complex. SMAD4 mutations give rise to juvenile polyposis syndrome, which is clinically similar to PJS. Our data suggest an unsuspected mechanistic link between these two syndromes.

AMP-Activated Protein Kinase Kinases↗
PubMed2001

The Wnt/beta-catenin pathway posteriorizes neural tissue in Xenopus by an indirect mechanism requiring FGF signalling.

In order to identify factors involved in posteriorization of the central nervous system, we undertook a functional screen in Xenopus animal cap explants which involved coinjecting noggin RNA together with pools of RNA from a chick somite cDNA library. In the course of this screen, we isolated a clone encoding a truncated form of beta-catenin, which induced posterior neural and dorsal mesodermal markers when coinjected with noggin in animal caps. Similar results were obtained with Xwnt-8 and Xwnt-3a, suggesting that these effects are a consequence of activating the canonical Wnt signalling pathway. To investigate whether the activation of posterior neural markers requires mesoderm induction, we performed experiments using a chimeric inducible form of beta-catenin. Activation of this protein during blastula stages resulted in the induction of both posterior neural and mesodermal markers, while activation during gastrula stages induced only posterior neural markers. We show that this posteriorizing activity occurs by an indirect and noncell-autonomous mechanism requiring FGF signalling.

Animals↗
PubMed2001

Arkadia enhances nodal-related signalling to induce mesendoderm.

Nodal-related members of the transforming growth factor (TGF)-beta family regulate the induction of mesoderm, endoderm, and mesendoderm, a tissue specific to the Spemann organizer. How these different tissues form in response to the same signalling molecules is not completely understood. It has been suggested that concentration-dependent effects, mediated by extracellular cofactors and antagonists, are responsible for the differences. Here we show that the nuclear protein Arkadia specifically potentiates the mesendoderm-inducing activity of a subset of TGF-beta family members. The combined activities of Arkadia and Xenopus nodal-related-1 are sufficient to induce mesendoderm and suppress mesoderm. Arkadia dorsalizes ventral tissues, resulting in the induction of organizer-specific gene expression. Blocking nodal signalling extracellularly inhibits these effects. Arkadia influences nodal activity when co-expressed and can function in cells adjacent to those producing the nodal signal. Our findings, together with the observation that Arkadia mutant mice lack a node and node-derived mesendoderm, identify Arkadia as an essential modulator of the nodal signalling cascade that leads to induction of Spemann's organizer.

Animals↗
PubMed2001

Capitation registration and social deprivation in England. An inverse 'dental' care law?

OBJECTIVE: To examine associations between NHS child dental registration data and area deprivation scores of English Health Authorities (N= 100) in 1996/97 and 1997/98. METHOD: The Department of the Environment index of local conditions and the Jarman Underpriviledge Area Score from the 1991 census were used to measure deprivation. Prior to September 1997, children got free dental treatment under a capitation scheme with an NHS dentist. If they did not attend within 24 months their registration lapsed on the last day of December of the second registration year and they were deleted from the capitation list. After September 1997 the registration period was reduced to 15 months. OUTCOME: Curve-linear regression of the Health Authority (HA) percentage of children registered, lapses in capitation registrations and deprivation scores. RESULTS: In England 68% of children were registered in December 1996. The percentage registered in each Health Authority was associated with deprivation (DoE, r2=0.33, Jarman, r2=0.27 p<0.01). In January 1997, 17.8% (1,345,142) of children registered lapsed (HA range 12.8% to 30.3%) and this was also significantly associated with deprivation (DoE r2=0.66, Jarman, r2=0.51 p<0.01). Similar results were found in 1997/98. CONCLUSIONS: Registration and lapse rates were significantly associated with social deprivation confirming that there is an inverse 'dental' care law for children in England. NHS capitation may widen dental health inequalities.

Adolescent↗
PubMed2001

Natal homing in a marine fish metapopulation.

Identifying natal origins of marine fishes is challenging because of difficulties in conducting mark-recapture studies in marine systems. We used natural geochemical signatures in otoliths (ear bones) to determine natal sources in weakfish (Cynoscion regalis), an estuarine-spawning marine fish, in eastern North America. Spawning site fidelity ranged from 60 to 81%, comparable to estimates of natal homing in birds and anadromous fishes. These data were in contrast to genetic analyses of population structure in weakfish. Our findings highlight the need for consideration of spatial processes in fisheries models and have implications for the design of marine reserves in coastal regions.

Animals↗
PubMed2000

Oligomerization and oxide formation in bismuth aryl alkoxides: synthesis and characterization of Bi4(mu 4-O)(mu-OC6F5)6(mu 3-OBi(mu-OC6F5)3)2(C6H5CH3), Bi8(mu 4-O)2(mu 3-O)2(mu-OC6F5)16, Bi6(mu 3-O)4(mu 3-OC6F5)(mu 3-OBi(OC6F5)4)3, NaBi4(mu 3-O)2(OC6F5)9(THF)2, and Na2Bi4(mu 3-O)2(OC6F5)10(THF)2.

Exposing [Bi(OR)3(toluene)]2 (1, R = OC6F5) to different solvents leads to the formation of larger polymetallic bismuth oxo alkoxides via ether elimination/oligomerization reactions. Three different compounds were obtained depending upon the conditions: Bi4(mu 4-O)(mu-OR)6(mu 3-OBi(mu-OR)3)2(C6H5CH3) (2), Bi8(mu 4-O)2(mu 3-O)2(mu 2-OR)16 (3), Bi6(mu 3-O)4(mu 3-OR)(mu 3-OBi(OR)4)3 (4). Compounds 2 and 3 can also be synthesized via an alcoholysis reaction between BiPh3 and ROH in refluxing dichloromethane or chloroform. Related oxo complexes NaBi4(mu 3-O)2(OR)9(THF)2 (5) and Na2Bi4(mu 3-O)2(OR)10(THF)2 (6) were obtained from BiCl3 and NaOR in THF. The synthesis of 1 and Bi(OC6Cl5)3 via salt elimination was successful when performed in toluene as solvent. For compounds 2-6 the single-crystal X-ray structures were determined. Variable-temperature NMR spectra are reported for 2, 3, and 5.

Journal Article↗
PubMed2000

Water fluoridation, poverty and tooth decay in 12-year-old children.

AIM: To examine the influence of water fluoridation, and socio-economic deprivation on tooth decay in the permanent dentition of 12 year old children. SETTING: The North of England, fluoridated Newcastle and non-fluoridated Liverpool. A total of 6,638 children were examined. OUTCOME MEASURES: Multiple Regression analysis of fluoride status, mean electoral ward DMFT in 1992/93 and ward Townsend Scores from the 1991 census. RESULTS: Social deprivation and tooth decay were significantly correlated in areas with and without water fluoridation. Multiple linear regression showed a statistically significant interaction between ward Townsend score, mean DMFT and water fluoridation, showing that the more deprived the area the greater the reduction in tooth decay. At a Townsend score of zero (the English average) there was a predicted 37% reduction in decay in 12-year-olds in fluoridated wards. CONCLUSIONS: Tooth decay is strongly associated with social deprivation. The findings confirm that the implementation of water fluoridation has markedly reduced tooth decay in 12-year-old children and that socio-economic dental health inequalities are reduced.

Child↗
PubMed2000

Diminished secondary CTL response in draining lymph nodes on cutaneous challenge with herpes simplex virus.

We have shown that C57BL/6-derived CD8(+) CTL specific for an immunodominant herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) determinant express a highly conserved Vbeta10/junctional sequence combination. This extreme T cell receptor beta-chain bias can be used to track the activation of gB-specific CTL in lymph nodes draining the site of HSV-1 infection. In this report we have examined the accumulation of gB-specific CTL in the primary and secondary or recall CTL responses to HSV-1 infection. We found that gB-specific cytolytic activity present within popliteal lymph nodes draining HSV-infected foot-pads peaked at day 5 post-infection during the primary response. As found previously, this correlates with the accumulation of Vbeta10(+)CD8(+) CTL in the activated T cell subset. Lymph node-derived cytotoxicity peaked between days 3 and 4 on secondary challenge with virus and, somewhat surprisingly, was considerably below that seen in the primary response. This reduced gB-specific cytolytic activity mirrored a near absence of Vbeta10(+)CD8(+) T cell enrichment found within the draining lymph nodes during this recall response, consistent with the overall diminution of gB-specific CTL accumulation in this site. Finally, there was a second wave of biased accumulation of Vbeta10(+)CD8(+) activated T cells within the popliteal lymph nodes well after the resolution of infection in both the primary and secondary responses. These results are discussed in terms of preferential activation of virus-specific memory T cells directly in infected tissues during a secondary CTL response at the expense of draining lymphoid organs.

Animals↗
PubMed2000

Prevalence and severity of dental caries among American Indians and Alaska Natives.

OBJECTIVES: This paper reports findings from the 1991 IHS Patient Oral Health Status and Treatment Needs Survey (1991 IHS patient survey) and presents trends in caries among American Indian and Alaska Native (Native American) populations since 1957. METHODS: The 1991 IHS patient survey obtained data from approximately 10 percent (25,000) of the dental patients seen annually at IHS, tribal, and urban Indian clinics. The results of this survey are compared descriptively with previous surveys conducted by the IHS beginning in 1957. RESULTS: Findings from the 1991 IHS patient survey indicate that Native Americans experience a much higher prevalence of dental caries in their primary and permanent dentitions than the general US population. However, caries rates in Native American children peaked in 1983-84 and have been going down since that time. CONCLUSIONS: While progress has been made in preventing dental caries among Native Americans, the high prevalence and severity at all ages in this rapidly growing population have resulted in a large backlog of untreated disease with an overwhelming demand on the resources available to provide care. Continued emphasis on dental caries prevention and health promotion is an important part of the solution. New strategies such as targeting preventive services toward individuals and groups with the highest risk of disease and the use of modern conservative treatment methods to control disease must be employed. Full implementation of these strategies and identification of the resources required will depend upon new and ongoing partnerships among tribes, federal and state governments, and the private sector.

Adolescent↗
PubMed2000

Herpes simplex virus type 1-specific cytotoxic T-lymphocyte arming occurs within lymph nodes draining the site of cutaneous infection.

Various studies have shown that major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL) can be isolated from lymph nodes draining sites of cutaneous infection with herpes simplex virus type 1 (HSV-1). Invariably, detection of this cytolytic activity appeared to require some level of in vitro culture of the isolated lymph node cells, usually for 3 days, in the absence of exogenous viral antigen. This in vitro "resting" period was thought to represent the phase during which committed CD8(+) T cells become "armed" killers after leaving the lymph nodes and prior to their entry into infected tissue as effector CTL. In this study we reexamined the issue of CTL appearance in the HSV-1 immune response and found that cytolytic activity can be isolated directly from draining lymph nodes, although at levels considerably below those found after in vitro culture. By using T-cell receptor elements that represent effective markers for class I-restricted T cells specific for an immunodominant glycoprotein B (gB) determinant from HSV-1, we show that the increase in cytotoxicity apparent after in vitro culture closely mirrors the expansion of gB-specific CTL during the same period. Taken together, our results suggest that HSV-1-specific CTL priming does not appear to require any level of cytolytic machinery arming outside the lymph node compartment despite the absence of any detectable infection within that site.

Animals↗
PubMed2000

Hex is a transcriptional repressor that contributes to anterior identity and suppresses Spemann organiser function.

One of the earliest markers of anterior asymmetry in vertebrate embryos is the transcription factor Hex. We find that Hex is a transcriptional repressor that can be converted to an activator by fusing full length Hex to two copies of the minimal transcriptional activation domain of VP16 together with the flexible hinge region of the (lambda) repressor (Hex-(lambda)VP2). Retention of the entire Hex open reading frame allows one to examine Hex function without disrupting potential protein-protein interactions. Expression of Hex-(lambda)VP2 in Xenopus inhibits expression of the anterior marker Cerberus and results in anterior truncations. Such embryos have multiple notochords and disorganised muscle tissue. These effects can occur in a cell non-autonomous manner, suggesting that one role of wild-type Hex is to specify anterior structures by suppressing signals that promote dorsal mesoderm formation. In support of this idea, over-expression of wild-type Hex causes cell non-autonomous dorso-anteriorization, as well as cell autonomous suppression of dorsal mesoderm. Suppression of dorsal mesoderm by Hex is accompanied by the down-regulation of Goosecoid and Chordin, while induction of dorsal mesoderm by Hex-(lambda)VP2 results in activation of these genes. Transient transfection experiments in ES cells suggest that Goosecoid is a direct target of Hex. Together, our results support a model in which Hex suppresses organiser activity and defines anterior identity.

Animals↗
PubMed1999

Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains.

Detailed characterisation of six inbred strains of mice commonly used in transgenic and knockout research was carried out using a battery of behavioural tests (SHIRPA) followed by discriminant analysis of the data. In the primary observation screen, DBA/2 mice were relatively irritable and vocalised during handling. C57BL/6 were hyperactive as measured by transfer arousal, arena activity and touch-escape tests. By contrast, C3H were markedly hypoactive, had significantly enhanced grip strength and were also significantly impaired on the visual placing task. In the elevated plus-maze, BALB/c mice showed the highest level of open arm entries and time spent in the open arms, indicating the lowest level of anxiety. There was a clear dissociation of strains on exploratory activity, as measured in the holeboard test and spontaneous locomotor activity (LMA). DBA/2 mice were hyperactive in LMA but demonstrated relatively low levels of holeboard exploration. None of the six strains learnt the water maze spatial learning task particularly well. C57BL/6 and 129/Sv demonstrated most ability and C3H showed no evidence of having acquired the task. The SHIRPA screening battery and discriminant analysis of the data have enabled us to determine the relevant contribution of a number of behavioural measurements to the marked differences in phenotype of mouse strains. These data confirm the importance of carrying out a comprehensive profile in order to accurately characterise the phenotype of gene-targeted and transgenic mice.

Animals↗
PubMed1999

Photofrin photodynamic therapy for treatment of AIDS-related cutaneous Kaposi's sarcoma.

OBJECTIVE: Kaposi's sarcoma, the most common malignancy in AIDS patients, often presents with painful cutaneous lesions that are difficult to treat effectively despite a wide variety of therapeutic approaches. We used photodynamic therapy in an attempt to provide effective palliative treatment for this disease. METHODS: Photodynamic therapy utilizes the activation by light of a photosensitizing drug that preferentially accumulates in tumor tissue such as Kaposi's sarcoma. We enrolled 25 patients who received 1.0 mg/kg of Photofrin 48 h before exposure to 100-400 J/cm2 of 630 nm light. RESULTS: Of the 348 lesions treated, 289 were evaluable: 32.5% had complete clinical response, 63.3% had partial clinical response and 4.2% were clinical failures. There was a strong correlation between response and light dose: 54% of lesions achieved a complete clinical response at optimum light dose (> 250 J/cm2). There was no correlation of response with CD4 cell count nor was there a change in CD4 cell count post-treatment. At 400 J/cm2 full field scabbing and necrosis occurred in 90% of the treated fields. Thus, the maximum tolerated dose was determined to be 300 J/cm2. At light doses of 250 J/cm2 and below the toxicities were limited to erythema and edema in the treatment field. Forty-three biopsies were taken 0.5 h to 4 months post-treatment. These showed little change in the B and T cell infiltrates identified. Kaposi's sarcoma cells disappeared post-treatment in certain lesions. CONCLUSION: Photofrin is effective palliative treatment for HIV-associated Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1999

An anterior signalling centre in Xenopus revealed by the homeobox gene XHex.

BACKGROUND: Signals from anterior endodermal cells that express the homeobox gene Hex initiate development of the most rostral tissues of the mouse embryo. The dorsal/anterior endoderm of the Xenopus gastrula, which expresses Hex and the putative head-inducing gene cerberus, is proposed to be equivalent to the mouse anterior endoderm. Here, we report the origin and signalling properties of this population of cells in the early Xenopus embryo. RESULTS: Xenopus anterior endoderm was found to derive in part from cells at the centre of the blastocoel floor that express XHex, the Xenopus cognate of Hex. Like their counterparts in the mouse embryo, these Hex-expressing blastomeres moved to the dorsal side of the Xenopus embryo as gastrulation commenced, and populated deep endodermal adjacent to Spemann's organiser. Experiments involving the induction of secondary axes confirmed that XHex expression was associated with anterior development. Ventral misexpression of XHex induced ectopic cerberus expression and conferred anterior signalling properties to the endoderm. Unlike the effect of misexpressing cerberus, these signals could not neuralise overlying ectoderm. CONCLUSIONS: XHex expression reveals the unexpected origin of an anterior signalling centre in Xenopus, which arises in part from the centre of the blastula and localises to the deep endoderm adjacent to Spemann's organiser. Signals originating from these endodermal cells impart an anterior identity to the overlying ectoderm, but are insufficient for neural induction. The anterior movement of Hex-expressing cells in both Xenopus and mouse embryos suggests that this process is a conserved feature of vertebrate development.

Animals↗
PubMed1999

The relationship between water fluoridation and socioeconomic deprivation on tooth decay in 5-year-old children.

AIM: To examine the relationship between water fluoridation, socioeconomic deprivation and tooth decay in 5-year-olds. SETTING: 10,004 children: 1,051 in naturally fluoridated Hartlepool in 1991/92, 3,816 in fluoridated Newcastle & North Tyneside and 5,137 in non-fluoridated Salford & Trafford in 1993/94. OUTCOME MEASURES: Correlations between mean electoral ward dmft and ward Townsend Scores from the 1991 census. RESULTS: Regardless of the level of water fluoridation significant correlations were found between deprivation and tooth decay. Multiple linear regression models for dmft showed a statistically significant interaction between ward Townsend score, and both types of water fluoridation, confirming the more deprived the area the greater the reduction in tooth decay. At a Townsend score of zero (the English average) there was a predicted 43% reduction in decay in 5-year-olds in fluoridated areas. CONCLUSIONS: Tooth decay is strongly associated with social deprivation. The findings confirm that the implementation of water fluoridation has halved tooth decay in 5-year-old children and that the dental caries divide between rich and poor is reduced.

Child, Preschool↗
PubMed1999

BMP signalling in early Xenopus development.

Bone morphogenetic proteins (BMPs) are typically members of the transforming growth factor beta (TGF-beta) family with diverse roles in embryonic development. At least five genes with homology to BMPs are expressed during Xenopus development, along with their receptors and intracellular signalling pathways. The evidence suggests that BMPs have roles to play in both mesoderm induction and dorsoventral patterning. Studies in Xenopus have also identified a number of inhibitory binding proteins for the classical BMPs, encoded by genes such as chordin and noggin. These proteins appear to be responsible for establishing a morphogen gradient of BMP4 activity, which specifies different dorsoventral fates in early gastrulae. An emerging theme is that inhibition of BMP signalling is an important mechanism regulating cell fate decisions in early development.

Animals↗
PubMed1999

Pseudo-proteinuria following gelofusine infusion.

Transient massive proteinuria following cardiopulmonary bypass surgery was observed. It was characterized and attributed to post-operative gelofusine infusion. Gelofusine was found to interfere with dye binding but not immunochemical assays of proteinuria. Proteinuria following gelofusine infusion may not reflect underlying glomerular pathology.

Cardiopulmonary Bypass↗