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Biomedical subjects

J M Jones

Publications and source records attributed to J M Jones.

At least 73 records · Page 4Linked to original sources
PubMed1997

Communication of ClpXP protease hypersensitivity to bacteriophage Mu repressor isoforms.

The immunity repressor (Rep) of bacteriophage Mu establishes and maintains lysogeny by shutting down transposition functions needed for phage DNA replication. Although Rep is stable in vivo, an altered immunity repressor (Vir) encoded by virulent, trans-dominant Mu mutants is rapidly degraded by Escherichia coli ClpXP protease. Rep and Vir are degraded at approximately the same maximal velocity (Vmax) by ClpXP, but the Km for Rep (3.6 microM) is over 20-fold higher than the Km for Vir (0.15 microM). Rep is also highly resistant to degradation in the presence of DNA whereas Vir is not. Vir increases the rate of Rep degradation by reducing its Km and imparts to Rep ClpXP sensitivity in the presence of DNA. Vir can drive at an accelerated rate the complete degradation of Rep molecules that outnumber Vir by eightfold or more. So long as Vir is present at a concentration of 0.1 microM or higher, Rep is degraded with a Km that is indistinguishable from that of Vir. These characteristics of repressor may be an important means of transducing physiological signals that induce Mu transposition in response to growth conditions or environmental stress, ClpXP hypersensitivity being disseminated among Rep molecules for the induction of Mu transposition.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1997

Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse.

Ca2+ channel beta subunits regulate voltage-dependent calcium currents through direct interaction with alpha 1 subunits. The beta- and alpha 1-binding motifs are conserved, and all beta subunits can stimulate current amplitude, voltage dependence, and kinetics when coexpressed with various alpha 1 subunits. We used a positional candidate approach to determine that the ataxia and seizures in the lethargic (lh) mouse arise from mutation of the beta-subunit gene Cchb4 on mouse chromosome 2. A four-nucleotide insertion into a splice donor site results in exon skipping, translational frameshift, and protein truncation with loss of the alpha 1-binding site. The lethargic phenotype is the first example of a mammalian neurological disease caused by an inherited defect in a non-pore-forming subunit of a voltage-gated ion channel.

Amino Acid Sequence↗
PubMed1997

Cardiopulmonary arrest in general wards: a retrospective study of referral patterns to an intensive care facility and their influence on outcome.

OBJECTIVE: To analyse the effect on outcome of referral to specialist facilities after cardiopulmonary arrest in a general ward. METHODS: A retrospective analysis of resuscitation records of 743 patients in whom cardiopulmonary resuscitation was performed in a general ward between 1988 and 1992. After successful initial cardiopulmonary resuscitation, patients were identified as transferred to coronary care unit (CCU) or intensive care unit (ITU), or as staying in a general ward. MAIN OUTCOME MEASURE: Survival to discharge home. RESULTS: There were 322 initial survivors, of whom 148 (20% of the overall total) survived to be discharged from hospital; 63% of those transferred to CCU and 48% of those transferred to ITU survived to discharge, compared with 28% of those who stayed on the ward (P < 0.001). Of those aged less than 65 years, 75% survived to discharge after transfer to CCU and 54% after transfer to ITU, compared with 44% of those who stayed on the ward (P = 0.023); the respective figures for those over 65 years were: CCU 25%, ITU 34%, ward 25% (P = 0.014). Only half of those aged more than 65 years were transferred to a specialist facility, compared with 90% of those aged less than 65. CONCLUSIONS: Transfer to a specialist care facility after resuscitation from cardiopulmonary arrest has an influence on outcome. Age as an independent factor is not an appropriate criterion to use in deciding on transfer. The decision to arrange transfer must always be taken by the most experienced person available, and in line with peer reviewed guidelines.

Age Factors↗
PubMed1997

Direct measurement of flow from the posterior lymph hearts of hydrated and dehydrated toads (Bufo marinus).

Flow from the posterior lymph hearts of Bufo marinus was measured using Doppler flow probes. These probes were placed on the posterior vertebral vein and recorded flow as lymph was ejected from the heart. In resting, hydrated toads, mean lymph flow from one of the paired posterior lymph hearts was 25.9 +/- 4.9 ml kg-1 h-1, stroke volume was 8.9 +/- 1.4 microL kg-1 and lymph heart rate was 47.5 +/- 3.7 beats min-1. We estimate that, together, the paired posterior lymph hearts are capable of generating flows that are approximately one-sixtieth of the resting cardiac output. Mean peak systolic pressure developed by the posterior lymph hearts was 1.62 +/- 0.08 kPa. Simultaneous measurements of lymph heart pressure development and flow revealed that the outflow pore of the heart opened at a pressure of 0.71 +/- 0.04 kPa, approximately 113 +/- 5 ms into systole. When toads were moderately disturbed, stroke volume increased by as much as fourfold with little change in lymph heart rate (< 5 beats min-1). When toads were dehydrated, lymph flow decreased by 70% at 12h and by 80% and 24h. Since there was only a modest non-significant decrease in lymph heart rate (30%), this reduction in flow was attributed to decreases in stroke volume (approximately 80%). Lymph heart flow and stroke volume returned to control values 30 min after adding water back into the experimental chamber. Stroke volume was clearly more important in regulating lymph flow than lymph heart rate under these conditions in Bufo marinus.

Animals↗
PubMed1997

Ion channel mutations in mouse models of inherited neurological disease.

Analysis of the molecular defects in mouse mutants can identify candidate genes for human neurological disorders. During the past 2 years, mutations in sodium channels, calcium channels and potassium channels have been identified by positional cloning of the spontaneous mouse mutants motor endplate disease, tottering, lethargic and weaver. The phenotypes of four allelic mutations identified in the sodium channel gene Scn8a range from ataxia and muscle weakness through severe dystonia and progressive paralysis, indicating that human mutations in this gene could be associated with a variety of clinical syndromes. Mutations of the calcium channel subunits beta 4 in the lethargic mouse and alpha 1A in the tottering mouse have specific effects on cerebellar function. Targeted mutation of ligand-gated ion channels has also been used to generate new models of neurological disease. We will review these recent achievements and their implications for human neurological disease. The mouse studies indicate that mutations in ion channel genes are likely to be responsible for a broad spectrum of clinical phenotypes in human neurological disorders.

Alleles↗
PubMed1997

Toward standardization of health information.

NCVHS has made recommendations to the DHHS to standardize 42 core health data elements, a number of which relate to medical conditions and services. The committee has asked the DHHS Data Council to actively promote, both within the department and externally, standardization of data elements and definitions where substantial consensus already exists. For those elements that have been recognized as significant core data elements, but for which there is not consensus on approach or definition, the NCVHS is recommending that the Data Council support the formation of a public-private working group to conduct further study and evaluation. This group, or a separate group, could also be the focus for evaluating additions to the list of core data elements and for setting up methods for testing and promulgating the final products. The coming 12-18 months will be exceedingly important for health data standardization efforts in the US as the DHHS responds to both the NCVHS recommendations and the legislation recently enacted by Congress.

Abstracting and Indexing↗
PubMed1997

Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation without affecting apoptosis.

Loss or mutation of p53 may have multiple biological and genetic effects that result in accelerated tumor progression. Loss of p53 in some tumors has been correlated with a marked decrease in tumor cell apoptosis. p53 loss may also accelerate tumor growth through an increase in cell proliferation rates. To examine the effects of p53 loss on tumor progression in a controlled experimental context, we previously crossed p53-deficient mice to mammary tumor-susceptible Wnt-1 transgenic (TG) mice. The resulting female Wnt-1 TG offspring of this cross all developed mammary tumors, regardless of p53 status (p53+/+, p53+/-, or p53-/-). However, female p53-/- Wnt-1 TG mice developed tumors much sooner than their p53+/+ counterparts. In this report, we demonstrate that the average growth rates of tumors missing (p53-/-) or losing p53 (p53+/- with loss of heterozygosity) are accelerated compared to tumors with both wild-type p53 alleles (p53+/+). This accelerated growth rate appears to be due primarily to increases in rates of tumor cell proliferation. Tumor cell apoptotic levels were modest and were not measurably different in the presence or absence of wild-type p53. These results differ substantially from other mouse tumor models in which p53 loss was closely correlated with accelerated growth rates through attenuated apoptosis. Thus, the mechanisms by which p53 loss influences tumor progression may differ, depending on the tissue type and/or the oncogenic pathways involved.

Animals↗
PubMed1996

Latex allergen levels of injectable collagen stored in syringes with rubber plungers.

OBJECTIVES: To assess the latex allergen content of glutaraldehyde cross-linked injectable bovine collagen stored in rubber plunger syringes. METHODS: Extracts of syringe plungers and collagen solutions before and after storage in syringes with natural rubber latex plungers were tested for latex protein allergens. Thirty-nine patients known to be allergic to latex underwent skin prick testing with extracts of the latex plungers, collagen solutions before and after storage in syringes, standard latex skin test reagents, four extracts from commercially available gloves, and positive (histamine) and negative (diluent) control solutions. Thirty-one control patients not known to be latex allergic were similarly tested. RESULTS: No latex proteins were detected using in vitro immunochemical techniques. Only 1 of 39 (2.5%) latex allergic patients reacted to the syringe extract and the collagen stored in the syringe. No reactions were recorded to collagen that no contact with latex. CONCLUSIONS: The level of latex antigens in injectable collagen is very low. The low prevalence of skin test reactivity in these highly latex allergic individuals suggests that type 1 hypersensitivity reactions as a result of latex contamination would be unlikely.

Allergens↗
PubMed1996

Trophectoderm projections: a potential means for locomotion, attachment and implantation of bovine, equine and human blastocysts.

The behaviour of bovine, equine and human blastocysts was studied in vitro by time-lapse videomicrography and computer imaging. This study revealed that cytoplasmic extensions of the trophectoderm ['trophectoderm projections' (TEP)] were expressed by embryos of all three species, prior to or during zona escape. Bovine and human blastocysts escaped their zonae with a combination of blastocoele expansion, collapse and re-expansion coupled with the penetration of the zona pellucida by TEP. In equine embryos, after several cycles of blastocoele expansion and collapse, trophectoderm ruptured the zona with the concomitant appearance of TEP. This study provides documentation that TEP are expressed by a diverse range of mammalian species, bringing the total number of species in which this phenomenon is found to six, since TEP are also known to be expressed by guinea-pig, hamster and rhesus monkey blastocysts, representing rodents, ungulates and primates. In all species studied, the dynamic nature (extension, retraction, and angular movement) of the TEP was similar, moving in an undulating manner with rapid cycles of extension and retraction. Because TEP appear to be a general feature of mammalian blastocysts, they are implicated in one or more key events in early development, namely zona escape, attachment and/or implantation.

Animals↗
PubMed1996

Twin transfusion syndrome: reassessment of ultrasound diagnosis.

OBJECTIVE: To assess the antenatal ultrasonic diagnosis of the twin transfusion syndrome, an enigmatic disorder that results in an imbalance in the blood flow between monochorionic twins. STUDY DESIGN: Retrospective review of 16 cases of twin transfusion syndrome confirmed by placental pathology and neonatal data. RESULTS: A disparity in antenatal fetal weights, size difference between the two amniotic sacs and a single placenta were present in 81% (13/16) of confirmed cases. The finding of two separate umbilical cords with a disparity in the size or number of vessels was rare. Evidence of hydrops in either fetus or findings of congestive cardiac failure in the recipient twin were uncommon. CONCLUSION: Our data strongly suggest that the twin transfusion syndrome can be diagnosed in a significant number (81%) of cases. The syndrome is variable, and it is rare to observe all the diagnostic criteria in one case.

Adult↗