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Biomedical subjects

J Blake

Publications and source records attributed to J Blake.

At least 19 recordsLinked to original sources
PubMed2005

Reliability and validity of the CMT neuropathy score as a measure of disability.

OBJECTIVE: To determine the validity and reliability of the Charcot-Marie-Tooth disease (CMT) neuropathy score (CMTNS) in patients with inherited neuropathy. BACKGROUND: Natural history studies and potential treatment trials for patients with various forms of CMT are limited by the lack of quantitative methodologies to monitor disease progression. Most cases of CMT can be considered length-dependent axonal neuropathies because disability for even the demyelinating forms correlates with length-dependent axonal degeneration. The total neuropathy score (TNS) is a validated composite measure of disability in length-dependent axonal neuropathies but is weighted toward predominantly sensory neuropathies. Thus, the authors have devised a CMTNS, modified from the TNS, to provide a single measure to quantify CMT disability. METHODS: The authors measured inter- and intrainvestigator reliability of the CMTNS and performed a validation of the score with the Neuropathy Impairment Score (NIS), patient self-assessment scores, an ambulation index, and other measures of disability. RESULTS: Inter- and intrainvestigator reliability was more than 95% in the 60 patients evaluated. Patients could be divided into mild (CMTNS, < or =10), moderate (CMTNS, 11 to 20), and severe (CMTNS, > or =21) categories and demonstrated excellent correlations among all measures of disability. CONCLUSION: The Charcot-Marie-Tooth disease (CMT) neuropathy score is a validated measure of length-dependent axonal and demyelinating CMT disability and can be investigated as an end point for longitudinal studies and clinical trials of CMT.

Action Potentials↗
PubMed2003

Aberrant PAX3 and PAX7 expression. A link to the metastatic potential of embryonal rhabdomyosarcoma and cutaneous malignant melanoma?

Transcription factors encoded by PAX3 and PAX7 are amongst the first expressed in the embryo, being principal regulators of neurogenic and myogenic progenitor cell specification and embryonic segmentation. The basis for this review lies in the supposition that genetic programs for cell migration, thought regulated by PAX3 and PAX7 during embryonic development, become tools used by the metastatic cell. In highly metastatic neoplasms arising from cells of neurogenic and myogenic lineages such as embryonal rhabdomyosarcoma and cutaneous malignant melanoma, markedly high expression levels of PAX3 and PAX7 support this supposition. As PAX3 and PAX7 are known to play a role in the regulation of migratory events in embryogenesis, it is possible that the metastatic potential of these tumours is directly linked to migratory properties conferred them through PAX expression. Here we provide a novel perspective by correlating metastasis with expression of PAX3, PAX7 and ephrin/Eph receptors as well as NCAMs, cell surface markers normally involved in migration and adhesion during development, and propose a role for PAX genes in the increased metastatic potential of these tumours.

Animals↗
PubMed2002

Six novel connexin32 (GJB1) mutations in X-linked Charcot-Marie-Tooth disease.

X-linked Charcot-Marie-Tooth disease (CMTX) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX, as in other forms of Charcot-Marie-Tooth disease (CMT), are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Motor nerve conduction velocity is reduced. In male patients it is often less than 38 m/s in the median nerve (a value often used to distinguish between "demyelinating" and "axonal" forms of CMT), but in female patients conduction velocity may be faster than this or normal. Mutations in the connexin32 (gap junction protein beta 1 (GJB1)) gene are responsible for the majority of CMTX cases. This report describes six British CMTX families with six novel mutations (four missense, one nonsense, and one frame shift) of the GJB1 gene. Affected members in these six families had typical signs of CMT but in some affected members of three families there was additional central nervous system involvement or deafness in the absence of any other explanation other than CMT.

Adolescent↗
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2001

Diffusion of paramagnetically labeled proteins in cartilage: enhancement of the 1-D NMR imaging technique.

Quantifying the diffusive transport of large molecules in avascular cartilage tissue is important both for planning potential pharamacological treatments and for gaining insight into the molecular-scale structure of cartilage. In this work, the diffusion coefficients of gadolinium-DTPA and Gd-labeled versions of four proteins-lysozyme, trypsinogen, ovalbumin, and bovine serum albumin (BSA) with molecular weights of 14,300, 24,000, 45,000, and 67,000, respectively-have been measured in healthy and degraded calf cartilage. The experimental technique relies on the effect of the paramagnetic on the relaxation properties of the surrounding water, combined with the time course of a 1-dimensional spatial profile of the water signal in the cartilage sample. The enhanced technique presented here does not require a prior measurement of the relaxivity of the paramagnetic compound in the sample of interest. The data are expressed as the ratio of the diffusion coefficient of a compound in cartilage to its diffusion coefficient in water. For healthy cartilage, this ratio was 0.34 +/- 0.07 for Gd-DTPA, the smallest compound, and fell to 0.3 +/- 0.1 for Gd-lysozyme, 0.08 +/- 0.04 for Gd-trypsinogen, and 0.07 +/- 0.04 for Gd-ovalbumin. Gd-BSA did not appear to enter healthy cartilage tissue beyond a surface layer. After the cartilage had been degraded by 24-h trypsinization, these ratios were 0.60 +/- 0.03 for Gd-DTPA, 0.40 +/- 0.08 for Gd-lysozyme, 0.42 +/- 0.09 for Gd-trypsinogen, 0.16 +/- 0.14 for Gd-ovalbumin, and 0.11 +/- 0.05 for Gd-BSA. Thus, degradation of the cartilage led to increases in the diffusion coefficient of up to fivefold for the Gd-labeled proteins. These basic transport parameters yield insights on the nature of pore sizes and chemical-matrix interactions in the cartilage tissue and may prove diagnostically useful for identifying the degree and nature of damage to cartilage.

Algorithms↗
PubMed2001

Mineral and heavy metal status as related to a mortality event and poor recruitment in a moose population in Alaska.

Moose (Alces alces) found dead (FD) and hunter-killed (HK) in 1995 on the north slope of Alaska (USA) in the Colville River Drainage were evaluated for heavy metal and mineral status. Compared to previous reports for moose and domestic cattle, and data presented here from Alaska moose outside the Colville River area, levels of Cu were determined to be low in hoof, hair, liver, kidney, rumen contents, and muscle for these north slope moose. Iron (Fe) was low in muscle as well. These findings, in conjunction with evidence of poor calf survival and adult mortality prompted investigation of a mineral deficiency in moose (serum, blood, and hair) captured in the spring of 1996 and 1997. Captured males had higher Ca, Zn and Cu levels in hair than captured females. Female moose hair samples were determined to be low (deficient) in Cu, Ca, Fe, and Se with mean levels (ppm) of 2.77, 599.7, 37.4, and 0.30, respectively. Serum Cu level was low, and to a lesser degree Zn was deficient as well. Whole blood (1997 only) was marginally deficient in Se and all animals were deficient in Cu. Based on whole blood, sera and hair, Cu levels were considered low for moose captured in spring 1996 and 1997 in the Colville River area as compared to published data and other populations evaluated in this study. Low levels of ceruloplasmin activity support this Cu deficiency theory. Evidence indicates that these moose are deficient in Cu and other minerals; however, the remote location precluded sufficient examination of animals to associate this apparent deficiency with direct effects or lesions. Renal levels of Cd increased with age at expected levels.

Alaska↗
PubMed2000

Sleep in a community sample of elderly war veterans with and without posttraumatic stress disorder.

BACKGROUND: Although sleep disturbances are commonly reported by individuals with posttraumatic stress disorder (PTSD), objective findings have been inconsistent, due in part to small sample sizes, comorbid psychiatric disorders, variations in the recentness of trauma exposure, and the use of PTSD subjects involved in psychiatric treatment. METHODS: A community sample of elderly males (n = 59) exposed to war trauma 28-50 years ago and free from sleep-affecting medications and disorders other than PTSD completed 3 nights of polysomnography. Of these participants, 30 met criteria for current PTSD; three were receiving supportive outpatient psychotherapy. RESULTS: Two statistically significant differences were observed: Those with PTSD had a higher percentage of rapid eye movement (REM) sleep and fewer arousals from non-REM sleep. The perceptions of sleep quality among the participants with PTSD were lower than the perceptions of non-PTSD participants. Although participants with untreated obstructive sleep apnea and sleep movement disorders were not included in the sample, many cases were detected on initial screening. Treatment resulted in improved sleep and increased feelings of well being. CONCLUSIONS: Alterations in REM and arousals characterized PTSD in this sample. When comorbid sleep disorders were ruled out, sleep was clinically similar across the groups. Trauma-related sleep disturbances that subjects reported as arising early in the course of the disorder appear to have declined over time.

Aged↗
PubMed2000

Social costs of untreated opioid dependence.

Using cost-of-illness methodology applied to a comprehensive survey of 114 daily opiate users not currently in or seeking treatment for their addiction, we estimated the 1996 social costs of untreated opioid dependence in Toronto (Ontario, Canada). The survey collected data on social and demographic characteristics, drug use history, physical and mental health status, the use of health care and substance treatment services, drug use modality and sex-related risks of infectious diseases, sources of income, as well as criminality and involvement with the law enforcement system. The annual social cost generated by this sample, calculated at Canadian $5.086 million, is explained mostly by crime victimization (44.6%) and law enforcement (42.4%), followed by productivity losses (7.0%) and the utilization of health care (6.1%). Applying the $13,100 cost to the estimated 8,000 to 13,000 users and 2.456 million residents living in Toronto yields a range of social cost between $43 and $69 per capita.

Cost of Illness↗
PubMed2000

The influence of experience and specialisation on the reliability of a common clinical sign.

OBJECTIVES: To explore the influence of experience and specialisation on clinical judgement by comparing accuracy in diagnosing anaemia between a consultant general surgeon, a consultant ophthalmologist and their registrars. PATIENTS AND METHODS: Conjunctival inspection of 101 patients, subsequent correlation with haemoglobin concentration. MAIN OUTCOME MEASURES: Number of correct and incorrect diagnoses of anaemia. RESULTS: 54 patients were anaemic and 47 were not. Overall accuracy in diagnosing anaemia ranged from 0.61-0.69, sensitivity 0.52-0.65 and specificity 0.62-0.83. Agreements between pairs of examiners were 0.68-0.81, with kappa values of 0.36-0.60 when adjusted for chance agreement. CONCLUSIONS: Neither experience nor specialisation significantly influenced our ability to diagnose anaemia, based on conjunctival inspection. Without critical analysis of clinical signs, we are unaware of their diagnostic limitations.

Anemia↗
PubMed1999

Sympathetic overactivity from fenfluramine-phentermine overdose.

A 24-year-old male presented to the emergency department with hyperadrenergic manifestations of fenfluramine-phentermine overdose: tachycardia, mydriasis, fever, diaphoresis, hyperventilation, and combativeness. Sedatives, neuromuscular paralytics, adrenergic antagonists, and mechanical ventilation were required to care for the patient. In addition, the patient had self-inflicted 15% TBSA second-degree burns and developed adult respiratory distress syndrome which required continued intubation and mechanical ventilation for 12 days. The patient had split thickness skin grafts for his leg burns on day 11. He was discharged after a 26-day hospital stay. We are unaware of any previously reported cases of fenfluramine-phentermine overdose with such profound degree of sympathetic storm.

Adrenergic Antagonists↗
PubMed1998

Alternate-day buprenorphine dosing is preferred to daily dosing by opioid-dependent humans.

Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent outpatients and choice of alternate-day versus daily dosing was assessed. Four dosing schedules were presented in random order under blind and open dosing conditions. Subjects received two exposures to each dosing schedule. During daily dosing, subjects received maintenance doses every 24 h. During blind alternate-day dosing, subjects received double maintenance doses every 48 h; placebo was interposed on intervening days. During open alternate-day dosing, subjects received twice their maintenance dose on Monday, Wednesday and Friday and maintenance doses on Sunday. After completing two exposures to each dosing schedule, subjects chose either daily or alternate-day schedules each week for 1 month. Study participation was contingent on daily attendance and opioid abstinence. Ten subjects were exposed to the four conditions once. Seven subjects repeated these conditions and participated in the choice phase. The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions. Subjects' ratings of withdrawal, "sick" and sedation were lower during daily than during alternate-day dosing, but the difference between treatments was small. Nonetheless, subjects still chose alternate-day dosing on 96% of occasions, suggesting that the subject-rated differences between dosing schedules were not influential. These results extend prior findings to open-dosing conditions, and replicate the safety and acceptability of alternate-day buprenorphine treatment. Choice of alternate-day buprenorphine administration underscores the procedure's clinical utility and potential use as a positive reinforcer to enhance opioid treatment.

Adult↗
PubMed1998

The association between CD20 and Src-family Tyrosine kinases requires an additional factor.

CD20 is a B cell surface protein which can initiate intracellular signals involving tyrosine kinase activation, and modify B cell growth and differentiation. CD20 is tightly associated with the Src-family kinases Lyn, Fyn and Lck; however, the mechanism of interaction remains to be determined. Association between CD20 and Src-family kinases has been detected in peripheral blood B cells and in 5 out of 8 unrelated B cell lines. The lack of CD20-associated kinase activity in some cell lines offered an opportunity to investigate the mechanism of CD20 associations. All 8 B cell lines were found to express Lyn, and, with one exception, all cell lines also expressed Fyn. Lck, however, was not detected in any of the cell lines in which CD20 failed to coprecipitate kinase activity. To test the possibility that Lck was required for assembly of the CD20 complex, Lck was transfected into one of the 3 CD20/kinase association-deficient lines, namely T51. CD20 did not coprecipitate kinase activity from the transfected T51 cells, despite their expression of high levels of exogenous Lck, as well as endogenous Lyn and Fyn. CD20 cDNA from T51 was sequenced and found to be normal. These data establish that association between CD20 and Src-family kinases requires an additional factor.

Antigens, CD↗
PubMed1998

Liver failure associated with mitochondrial DNA depletion.

BACKGROUND/AIMS: Liver failure in infancy can result from several disorders of the mitochondrial respiratory chain. In some patients, levels of mitochondrial DNA are markedly reduced, a phenomenon referred to as mitochondrial DNA depletion. To facilitate diagnosis of this condition, we have reviewed the clinical and pathological features in five patients with mitochondrial DNA depletion. METHODS: Cases were identified by preparing Southern blots of DNA from muscle and liver, hybridising with appropriate probes and quantifying mitochondrial DNA relative to nuclear DNA. RESULTS: All our patients with mitochondrial DNA depletion died of liver failure. Other problems included hypotonia, hypoglycaemia, neurological abnormalities (including Leigh syndrome) and cataracts. Liver histology showed geographic areas of fatty change, bile duct proliferation, collapse of liver architecture and fibrosis; some cells showed decreased cytochrome oxidase activity. Muscle from three patients showed mitochondrial proliferation, with loss of cytochrome oxidase activity in some fibres but not in others; in these cases, muscle mitochondrial DNA levels were less than 5% of the median control value. The remaining two patients (from a single pedigree) had normal muscle histology and histochemistry associated with less severe depletion of mitochondrial DNA in muscle. CONCLUSIONS: Liver failure is common in patients with mitochondrial DNA depletion. Associated clinical features often include neuromuscular disease. Liver and muscle histology can be helpful in making the diagnosis. Mitochondrial DNA levels should be measured whenever liver failure is thought to have resulted from respiratory chain disease.

DNA, Mitochondrial↗
PubMed1998

Seasonal levels of metabolic hormones and substrates in male and female reindeer (Rangifer tarandus).

Seasonal levels of cortisol, growth hormone (GH), insulin like growth factor 1 (IGF-1), glucose, triiodothyronine (T3), free T3, thyroxine and free fatty acids (FFA) were measured every 3 weeks for 54 weeks in the plasma of five adult bulls, and four barren and five pregnant Alaskan reindeer (Rangifer tarandus) cows. Three consecutive samples were taken from each animal. Cortisol levels exhibited wide seasonal variation (9-45 ng/ml) [corrected] without any peak or difference in levels among groups. Rising levels were detected between the 3 consequent samples. Peak GH levels, detected during January and February, were higher in the non-pregnant group (54 ng/ml) than the pregnant (26 ng ml-1) and the male (27 ng ml-1) groups. Low GH levels (2-10 ng ml-1) were recorded between May and September. IGF-1 reached peak levels (715 ng ml-1) in males in August, in non-pregnant females in September (677 ng ml-1), and in the pregnant females in October (505 ng ml-1). Seasonal minima (404 in males, 172 and 93 in pregnant and non-pregnant groups) were detected in February. Glucose was fairly stable throughout the year (100-200 mg/100 ml). A rising levels were found between the three consecutive samples. Triiodothyronine (T3) (2.16-2.30 ng ml-1) peaked in all three groups during the spring and early summer, and minimal levels (0.61-0.97 ng ml-1) were detected from October to January. Conversely, thyroxine or free T3 did not exhibit seasonal variation. FFA fluctuated widely (97-1076 nmol l-1) throughout the year. Only in pregnant females were concentrations more stable (150-460 nmol l-1). Perhaps, because of ad libitum supply of food in captive reindeer, only T3 and GH exhibited pronounced seasonal fluctuations which could be related to the metabolic changes expected during the annual cycle.

Alaska↗