Support for carers. Somebody cares.
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Caregivers↗
Biomedical subjects
C Allen
Publications and source records attributed to C Allen.
Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by fluorescence in situ hybridization and somatic cell hybrid analysis.
Ror1 is an orphan cell surface receptor with strong homology to the tyrosine kinase domain of growth factor receptors, in particular the Trk family. Southern blot analysis of genomic DNA from somatic cell hybrids revealed that Ror1 is located on chromosome 1. We have mapped the Ror1 gene to chromosome 1p12-p32 using PCR on a somatic cell hybrid panel that subdivides chromosome 1p. We have further localized the gene to chromosome 1p31-p32 by fluorescence in situ hybridization using a PAC clone that contains the Ror1 gene.
Animals↗
ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers.
Mouse eck, a member of the EPH gene family, has been mapped to mouse chromosome 4. The syntenic relationship between this chromosome and human chromosome 1 suggests that the human ECK gene maps to the distal short arm of human chromosome 1 (1p). Since this region is frequently deleted or altered in certain tumors of neuroectodermal origin, it is important to define the specific chromosomal localization of the human ECK gene. PCR screening of a rodent-human somatic cell hybrid panel by ECK-specific primers showed that ECK is indeed localized to human chromosome 1. Additional PCR screening of a regional screening panel for chromosome 1p indicated that ECK is localized to 1p36, distal to FUCA1. Furthermore, fluorescence in situ hybridization analysis with an ECK-specific P1 clone showed that ECK maps proximal to genetic marker D1S228. Taken together, the data suggest that ECK maps to 1p36.1, a region that is frequently deleted in neuroblastoma, melanoma, and other neuroectodermal tumors.
Animals↗
Possible transmission of Blastomycosis dermatitidis via culture specimen.
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Animal Technicians↗
Blastomycosis in six dogs in New York state.
Blastomycosis was diagnosed in 6 dogs living in New York state. To our knowledge, blastomycosis has not been previously reported in dogs in this area, and maps that indicate the prevalence of blastomycosis in North America often partially or completely exclude the state of New York. Environmental characteristics implicated in previous blastomycosis outbreaks in people can be found in New York state, and this may explain how these dogs became infected. Blastomycosis develops in people as well as in dogs, and an understanding of the ecologic and clinical features of blastomycosis can help veterinarians counsel their clients in matters of public health.
Animals↗
Incidence of retinopathy and associated risk factors from time of diagnosis of insulin-dependent diabetes.
OBJECTIVE: To describe the prevalence at baseline and 4-year incidence of retinopathy and its relation to glycemic control from the time of diagnosis of insulin-dependent diabetes. DESIGN: Geographically defined population-based study. SETTING: Twenty-eight-county area in Wisconsin. STUDY POPULATION: Incipient cohort of children, teenagers, and young adults (n = 354) up to 30 years of age with newly diagnosed insulin-dependent diabetes. MAIN OUTCOME MEASURE: Diabetic retinopathy as determined by gradings from 30 degrees color stereoscopic photographs of the Diabetic Retinopathy Study 7 standard fields. RESULTS: The prevalence of retinopathy at diagnosis was 1.3%. Four years after diagnosis of diabetes, retinopathy was first identified in 5.1% of our cohort and in 9.7% of those 15 years of age or older. After controlling for age, subjects with a mean glycosylated hemoglobin level of 12% or greater were 3.2 times as likely (95% confidence interval, 1.1-9.9) to have retinopathy present at follow-up as were subjects with a mean glycosylated hemoglobin level of less than 12%. CONCLUSION: Population-based data on the frequency and incidence of retinopathy from the time of diagnosis of insulin-dependent diabetes mellitus provided by this study suggest a possible reduction in risk of developing retinopathy in those in whom glycemic control is achieved from the time of diagnosis.
Adolescent↗
Integrating mental health services within primary care. A Canadian program.
The increasingly prominent role of the family physician in delivering mental health care can be enhanced if productive and collaborative relationships can be established with local mental health services. This paper describes a Canadian program that has achieved this by bringing mental health counselors and psychiatrists into the offices of 87 family physicians in 35 practices in a community in Southern Ontario. The paper describes the program, the activities of counselors and psychiatrists within the practices, and the administrative structures set up to coordinate these activities. Data is presented from the evaluation of the first year of the program's operation (13 practices and 45 family physicians) during which time 3085 referrals were received. The program made mental health care more available and accessible, increased continuity of care, provided additional support for the family physician, offered new opportunities for continuing education, and led to a reduced and more efficient use of other mental health services. The components of the program can be adapted to most communities.
Adolescent↗
Molecular genetic analysis of familial neuroblastoma.
Neuroblastoma has several clinical and molecular genetic parallels with the other paediatric embryonal tumours, such as retinoblastoma, including a hereditary form of the disease. We hypothesised that neuroblastoma susceptibility is due to germline mutations in a tumour suppressor gene and that this predisposition gene may be involved in sporadic neuroblastoma tumorigenesis as well. We therefore aimed to localise the familial neuroblastoma predisposition gene by linkage analysis in neuroblastoma kindreds. Eighteen families segregating for neuroblastoma were ascertained for candidate locus linkage analysis. Although many of the 49 affected individuals in these families were diagnosed as infants with multifocal primary tumours, there was marked clinical heterogeneity. We originally hypothesised that familial neuroblastoma predisposition would map to the telomeric portion of chromosome band 1p36, a genomic region likely to contain a sporadic neuroblastoma suppressor gene. However, neuroblastoma predisposition did not map to any of eight polymorphic markers spanning 1p36.2-.3 in three large kindreds. In addition, there was strong evidence against linkage to two Hirschsprung disease susceptibility genes (RET and EDNRB), a condition that can cosegregate with neuroblastoma as in one of the kindreds tested here. We conclude that the neuroblastoma susceptibility gene is distinct from the 1p36 neuroblastoma suppressor and two of the currently identified Hirschsprung disease susceptibility genes.
Adult↗
Human Krüppel-related 3 (HKR3): a candidate for the 1p36 neuroblastoma tumour suppressor gene?
Human Krüppel-related 3 (HKR3) is a zinc finger gene that maps within chromosome subbands 1p36.2-.3, a region postulated to contain a tumour suppressor gene associated with advanced neuroblastomas. Genomic clones of HKR3 were isolated from a P1 library and physically mapped to within 40 kb of D1S214 at 1p36.3. The gene is ubiquitously expressed in human tissues, but especially high levels are present in human fetal and adult nervous tissues. Hemizygous deletion of HKR3 in a lymphoblastoid cell line derived from a neuroblastoma patient with a constitutional 1p36 interstitial deletion and in the neuroblastoma cell line SK-N-AS, which also has a small interstitial 1p36 deletion, has been observed. Allelic loss at D1S214 in 15/15 informative primary neuroblastoma specimens with 1p36 deletions has also been observed. In a panel of 16 neuroblastoma cell lines, no gross genomic DNA rearrangements were noted, the gene was always expressed (albeit at variable levels) and there was no evidence for truncating mutations. Furthermore, there were no mutations detected in the zinc finger coding region in four neuroblastoma cell lines with 1p deletions analysed by direct sequence analysis. We conclude that HKR3 is a novel zinc finger gene that maps to a region of the genome commonly rearranged or deleted in neuroblastoma and other human cancers.
Adult↗
Molecular analysis of the region of distal 1p commonly deleted in neuroblastoma.
Cellular, cytogenetic, and molecular evidence indicates that chromosome band 1p36 is often deleted in neuroblastoma cell lines and tumours, suggesting the presence of one or more tumour suppressor genes in this region. We used a multifaceted approach to analyse the commonly deleted region, 28 distal 1p-specific polymorphic loci were used to detect loss of heterozygosity (LOH) in a panel of primary neuroblastoma tumours. Thirty-two of 122 tumours (26%) demonstrated LOH at three or more loci. In addition, a patient with a constitutional deletion of 1p36.2-.3 and two neuroblastoma cell lines with 1p36 abnormalities were characterised by FISH. When combined with the LOH data, a single consensus region of deletion was defined proximally by PLOD and distally by D1S80, a region spanning approximately five megabases. Several proposed candidate tumour suppressor genes, including ID3, CDC2L1, DAN, PAX7, E2F2, TNFR2 and TCEB3, map outside of this region; however, the transcription factor HKR3 cannot be excluded. LOH for 1p is correlated with adverse clinical and biological features and a poor prognosis, but 1p LOH is not an independent predictor of overall survival. To identify additional candidate genes, an integrated physical map of 1p35-36 is being constructed. The current map includes 445 polymerase chain reaction (PCR)-formatted markers and 608 YACs. This map will help identify region-specific transcripts by direct selection and sequencing.
Chromosome Deletion↗
Human leptin levels are pulsatile and inversely related to pituitary-adrenal function.
Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese.
Adrenocorticotropic Hormone↗
Engraftment and outcomes of patients receiving myeloablative therapy followed by autologous peripheral blood stem cells with a low CD34+ cell content.
Engraftment kinetics after high-dose chemotherapy (HDC) were evaluated in patients receiving autologous peripheral blood stem cell (PBSC) infusions with a low CD34+ cell content. Forty-eight patients were infused with < 2.5 x 10(6) CD34+ cells/kg; 36 because of poor harvests and 12 because they electively received only a fraction of their harvested cells. A median of 2.12 x 10(6) CD34+ cells/kg (range, 1.17-2.48) were infused following one of seven different HDC regimens. All patients achieved absolute neutrophil counts > or = 0.5 x 10(9)/l at a median of day 11 (range, 9-16). Forty-seven patients achieved platelet counts > or = 20 x 10(9)/l at a median of day 14 (range, 8-250). Nine of 47 (19%) had platelet recovery after day 21, 4/47 (9%) after day 100 and one died on day 240 without platelet recovery. Twenty-six patients (54%) died of progressive disease in 51-762 days; 22 (46%) are alive at a median of 450 days (range, 94-1844), 17 (35%) of whom are surviving disease-free at a median of 494 days (range, 55-1263). No patient died as a direct consequence of low blood cell counts. These data demonstrate that PBSC products containing 1.17-2.48 x 10(6) CD34+ cells/kg resulted in relatively prompt neutrophil recovery in all patients but approximately 10% had delayed platelet recovery.
Antigens, CD34↗
Massive splenomegaly complicating left percutaneous renal surgery.
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Aged↗
Recurrent branch retinal infarcts in association with migraine.
Migraine has been blamed for a variety of temporary and permanent visual complications. We describe the case of a young woman with migraine who suffered recurrent episodes of retinal infarction, one of which occurred during an attack of migraine. The infarctions resulted from occlusions of branches of the central retinal artery. Extensive laboratory and radiological investigations failed to establish a nonmigrainous etiology. In some individuals, migraine may cause or promote branch retinal vaso-occlusion and infarction.
Adult↗
Multiparametric continuous monitoring of brain metabolism and substrate delivery in neurosurgical patients.
Brain function and tissue integrity are highly dependent on continuous oxygen supply and clearance of CO2. Aerobic metabolism is the major energy source to normal brain, however, during hypoxia and ischemia, lactate accumulation may sometimes be seen, indicating anaerobic glycolysis after severe head injury. Current monitoring techniques often fail to detect such events which can affect substrate delivery to the injured brain. We have recently adapted a method for continuous monitoring of brain tissue pO2, pCO2, pH and temperature, using a single sensor. The multiparameter sensor is inserted into brain tissue, via a new three lumen bolt, together with a standard ventriculostomy catheter and a microdialysis probe. The system has been left in place as long as needed, but never more than 7 days. All readings were compared to clinical parameters, and outcome. Stable measurements could be obtained in the first group of 20 patients, after calibration and rigid fixation, using the new bolt. Severely head injured patients had brain oxygen levels of less than 25-30 mmHg for the first hours after injury. Thereafter two patterns could be seen. Patients with favorable outcome had a slow increase in brain oxygen, and brain CO2 decreased to normal values, as long as the cerebral perfusion pressure (CPP) was kept above 70 mmHg. However, in those patients with secondary ischemic events, and bad outcome, a further decline in brain oxygen to anaerobic levels (< 20 mmHg) was seen. For these patients, both decreased and increased brain CO2 levels could be seen. Brain CO2 levels of 90-150 mmHg were consistently seen after brain death. Brain pH was inversely related to brain CO2 for all patients. Brain glucose and lactate in patients with poor outcome were 639 microM l-1 +/- 330, and 1642 microM l-1 +/- 788, whereas patients with good outcome had brain glucose levels of 808 microM l-1 +/- 321 and lactate levels of 1001 microM l-1 +/- 417. Extended neuromonitoring using a combined sensor for brain oxygen, CO2, pH and temperature measurements, as well as a microdialysis probe for glucose and lactate analysis may optimize the management of comatose neurosurgical patients in the future, by allowing a fuller understanding of dynamic factors affecting brain metabolism.
Acid-Base Equilibrium↗
The impact of social inequalities in child health on health visitors' work.
BACKGROUND: Preventive and health promotion work by health visitors ought to reduce social inequalities in child health. However, the increased health and developmental problems among disadvantaged children may constrain health visitors' ability to carry out effective preventive work. This paper measures the impact of socioeconomic inequalities in children's health on the work of health visitors and the amount of preventive work they can provide, with emphasis on 'parenting' programmes. METHODS: Data collected for health visitors' profiles were analysed in an ecological cross-sectional study. Individual caseloads were classified according to the proportions of families in social class IV or V and families headed by an unemployed person. A range of measures of young children's health and development indicated the demands on health visitors' time. Preventive work was divided into post-natal support, parenting programmes, special clinics and other preventive work. RESULTS: All the outcome measures were poorer in the most disadvantaged caseloads. Odds ratios between the most and least disadvantaged 20 per cent of caseloads were 0.6 for breast feeding at birth, and at seven months, 1.9 for post-natal depression, 3.2 for mothers under 18, 10 for lone parent families, 2.6 for families needing high intervention, 4.5 for families with a smoker, 11 for domestic violence, 4.4 for parents with a chronic health problem, 2.7 for children on the child protection register and 2.8 for children with developmental problems. There was 30 per cent greater health visitor time provided in the most disadvantaged caseloads than in the most advantaged. There was no consistent difference in the amount of preventive work carried out; in particular, parenting programmes were delivered at a similar rate in all caseloads. CONCLUSIONS: Large differences in demands on health visitors' time exist between affluent and disadvantaged caseloads which are barely reflected in the provision of extra time to poorer caseloads. There is no consistent pattern to the delivery of preventive programmes designed to ameliorate the effects of disadvantage on children's health and development.
Child↗
A regulatory locus, pehSR, controls polygalacturonase production and other virulence functions in Ralstonia solanacearum.
We previously identified a locus that regulates production of polygalacturonase (PG), an extracellular plant cell wall-degrading enzyme important in bacterial wilt of plants caused by Ralstonia (Pseudomonas) solanacearum. The DNA sequence of this locus, called pehSR, was determined and two consecutive open reading frames (ORFs) of 1,905 and 1,680 bp were identified. The amino acid sequences predicted to be encoded by these ORFs are similar to those of regulators of pilin synthesis in Pseudomonas aeruginosa and Myxococcus xanthus and to a regulator of flagellin synthesis and adhesion in P. aeruginosa, as well as to other two-component regulators of the NtrB/C subfamily. pehSR mutants produced negligible levels of endo-PG activity, while exo-PG activity was reduced by 50%. Northern (RNA) blot analysis showed that PehSR regulates endo-PG expression at the transcriptional level. pehSR mutants grew normally in culture and in planta but were dramatically reduced in virulence; this loss of virulence was substantially greater than that observed for endo-PG structural gene mutants, suggesting that pehSR regulates additional factors important in virulence. Although pehSR mutants were essentially nonmotile, like the wild-type strain, multiple copies of pehSR conferred motility on the bacterium. Reporter gene studies indicated that pehSR expression increased when bacteria grew in plant tissue, and that the pehSR locus was itself negatively regulated by the global virulence gene regulator PhcA.
Amino Acid Sequence↗
The spv genes on the Salmonella dublin virulence plasmid are required for severe enteritis and systemic infection in the natural host.
The pathogenic role of the spv (Salmonella plasmid virulence) genes of Salmonella dublin was determined in the natural, bovine host. Since the lack of overt signs of enteritis or enterocolitis due to Salmonella infections in mice has limited the development of a convenient experimental system to study enteric disease, we used calves to study the contribution of the spv genes to S. dublin-induced salmonellosis. Since the SpvR transcriptional regulator is required for expression of the spvABCD operon, we constructed an spvR knockout mutation in a calf-virulent strain of S. dublin. Calves were infected with the wild-type strain, an spvR mutant, and an spvR mutant containing a complementing plasmid. Calves that were infected with the wild type or the complemented spvR mutant rapidly developed severe diarrhea and became moribund. Calves that were infected with the spvR mutant showed little or no clinical signs of systemic salmonellosis and developed only mild diarrhea. The survival and growth of the wild-type strain and the spvR mutant were determined by using blood-derived bovine monocytes. Wild-type S. dublin survived and grew inside cells, while the spvR mutant did not proliferate. These results suggest that the spv genes of S. dublin promote enhanced intracellular proliferation in intestinal tissues and at extraintestinal sites in the natural host.
Animals↗