Use of an unstructured patient-held record in palliative care.
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Humans↗
Biomedical subjects
N Jones
Publications and source records attributed to N Jones.
The bacteriology of pulmonary tuberculosis in a population with high human immunodeficiency virus seroprevalence.
SETTING: A public sector urban university hospital in Soweto, South Africa. OBJECTIVE: To describe the utility of sputum smear microscopy and the prevalence of Mycobacterium tuberculosis resistance to antituberculosis drugs according to human immunodeficiency virus (HIV) serostatus in adults. DESIGN: A retrospective descriptive study of consecutive cases using a record review. RESULTS: We studied 412 adults with culture-proven pulmonary tuberculosis, of whom 185 (44.9%) were HIV-seropositive and had a significantly lower sputum smear positivity than HIV seronegatives (68% versus 79%, P < 0.05). Smear positivity was significantly higher in HIV-infected patients with CD4 counts < or = 50/mm3 compared to those with CD4 counts of 201-300/mm3 (P < 0.05). In patients with and those without a history of previous treatment for tuberculosis, resistance to one or more antituberculosis drugs was found in 32.2% and 13.6% of cases, respectively, while resistance to both isoniazid and rifampicin (multidrug-resistant tuberculosis [MDR]) was found in 15.3% and 4.5% of patients, respectively. There was no significant difference in resistance between HIV-positive and seronegative patients. CONCLUSION: A strong tuberculosis control programme and good surveillance will be required to prevent the further spread of MDR tuberculosis. Surveys such as these are useful for monitoring control programmes.
AIDS-Related Opportunistic Infections↗
Gonococcal endocarditis after a threatened abortion. A case report.
BACKGROUND: Disseminated gonocococcal infection arising during pregnancy is an uncommon occurrence. Gonococcemia following a threatened abortion has not been documented previously. CASE: Gonococcal arthritis and endocarditis in a 22-year-old primigravida occurred following a midtrimester threatened abortion. CONCLUSION: Since gonococcemia is thought to be secondary to endocervical disruption, chemoprophylaxis in the gravid cardiac patient after a threatened abortion is recommended.
Abortion, Threatened↗
Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial.
OBJECTIVES: To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls. DESIGN: 18 month, open randomised intervention trial. SUBJECTS: 82 white girls aged 12.2 (SD 0.3) years, recruited from four secondary schools in Sheffield. INTERVENTION: 568 ml (one pint) of whole or reduced fat milk per day for 18 months. MAIN OUTCOME MEASURES: Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry. Outcome measures to evaluate mechanism included biochemical markers of bone turnover (osteocalcin, bone alkaline phosphatase, deoxypyridinoline, N-telopeptide of type I collagen), and hormones important to skeletal growth (parathyroid hormone, oestradiol, insulin-like growth factor I). RESULTS: 80 subjects completed the trial. Daily milk intake at baseline averaged 150 ml in both groups. The intervention group consumed, on average, an additional 300 ml a day throughout the trial. Compared with the control group, the intervention group had greater increases of bone mineral density (9.6% v 8.5%, P = 0.017; repeated measures analysis of variance) and bone mineral content (27.0% v 24.1%, P = 0.009). No significant differences in increments in height, weight, lean body mass, and fat mass were observed between the groups. Bone turnover was not affected by milk supplementation. Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group (35% v 25%, P = 0.02). CONCLUSION: Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass.
Adolescent↗
Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins.
The passage of mammalian cells through the restriction point into the S phase of the cell cycle is regulated by the activities of Cdk4 and Cdk6 complexed with the D-type cyclins and by cyclin E/Cdk2. The activities of these holoenzymes are constrained by CDK inhibitory proteins. The importance of the restriction point is illustrated by its deregulation in many tumour cells and upon infection with DNA tumour viruses. Here we describe the properties of cyclins encoded by two herpesviruses, herpesvirus saimiri (HVS) which can transform blood lymphocytes and induce malignancies of lymphoid origin in New World primates, and human herpesvirus 8 (HHV8) implicated as a causative agent of Kaposi's sarcoma and body cavity lymphomas. Both viral cyclins form active kinase complexes with Cdk6 that are resistant to inhibition by the CDK inhibitors p16(Ink4a), p21Cip1 and p27Kip1. Furthermore, ectopic expression of a viral cyclin prevents G1 arrest imposed by each inhibitor and stimulates cell-cycle progression in quiescent fibroblasts. These results suggest a new mechanism for deregulation of the cell cycle and indicate that the viral cyclins may contribute to the oncogenic nature of these viruses.
3T3 Cells↗
Thymic regression and apoptosis in the rat after treatment with the Leydig cell cytotoxin ethylene dimethanesulphonate (EDS).
Ethylene dimethanesulphonate (EDS) is an alkylating agent which is widely assumed to specifically kill Leydig cells leaving other biological systems intact. However, after EDS treatment of the male rat the thymus reversibly involutes and the gonadal regional lymph nodes are activated. In the present experiments we have demonstrated that EDS has a direct action upon the thymus both in vivo and in vitro. EDS treatment of the intact and castrated male rat and the intact female rat caused regression of the thymus by up to 50% 3 days later. Total cellularity decreased while the proliferative index increased suggesting a compensatory mechanism. Thymocytes were exposed to EDS in vitro and the response compared to the glucocorticoid methylprednisolone (P), a well characterised thymic apoptotic stimulant. EDS and P increased apoptosis in the thymocyte as characterised by the appearance of cells containing nuclei with apoptotic morphology and with DNA fragmentation visualised by a characteristic ladder after agarose gel electrophoresis. The effects of both EDS and P were time and dose dependent but, in contrast to the effects in Leydig cells, P was the most effective apoptotic stimulus (for instance 100%-P compared to 30%-EDS or 7% control/DMSO after 24 h incubation). The immunological responses of the gonadal lymph nodes were not associated with testicular regression as it was seen in the castrated rat but may be related to a direct action upon the epididymis. In conclusion, tissue specificity of the Leydig cell cytotoxin needs to be extended to the thymus and epididymis. The mode of cell death in Leydig cells and thymocytes after both glucocorticoids and EDS is apoptosis which suggests that they possess some common mechanism(s) which is responsible for the toxicity of these diverse compounds.
Animals↗
Gulf War illness. Family doctors should be aware of assessment programme.
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Family Practice↗
Regulation of yAP-1 nuclear localization in response to oxidative stress.
The YAP1 gene of Saccharomyces cerevisiae encodes a bZIP-containing transcription factor that is essential for the normal response of cells to oxidative stress. Under stress conditions, the activity of yAP-1 is increased, leading to the induced expression of a number of target genes encoding protective enzymes or molecules. We have examined the mechanism of this activation. Upon imposition of oxidative stress, a small increase in the DNA-binding capacity of yAP-1 occurs. However, the major change is at the level of nuclear localization; upon induction the yAP-1 protein relocalizes from the cytoplasm to the nucleus. This regulated localization is mediated by a cysteine-rich domain (CRD) at the C-terminus, its removal resulting in constitutive nuclear localization and high level activity. Furthermore, the CRD of yAP-1 is sufficient to impose regulated nuclear localization of the GAL4 DNA-binding domain. Amino acid substitutions indicated that three conserved cysteine residues in the CRD are essential for the regulation. We suggest therefore, that these cysteine residues are important in sensing the redox state of the cell and hence regulating yAP-1 activity.
Amino Acid Sequence↗
Functional characterization of the fission yeast Start-specific transcription factor Res2.
In the fission yeast Schizosaccharomyces pombe, transcriptional activation at Start is mediated by complexes that bind the MCB. Two such complexes have been identified; both contain the Cdc10 protein in partnership with either the Res1 or Res2 protein. Characterization of null mutants suggests that the Res1-Cdc10 complex predominantly functions in mitotic cells whereas the Res2-Cdc10 complex is required for meiosis and spore formation. Here we have characterized the functional domains of the Res2 protein. The N-terminus is both necessary and sufficient for DNA binding, whereas the C-terminus is the region involved in the interaction with the Cdc10 protein. The centrally located ankyrin repeats are dispensable for both functions. Res2 binds to DNA as a dimer. In addition, complexes containing both Res1 and Res2 can form and bind to DNA in vitro. Furthermore, the major MCB-specific complex detected in extracts from wild-type cells contains Res1 and Res2; the complex is lost when either gene is deleted and can be recognized by antibodies specific to both proteins. In order to understand the basis for the specific function of Res2 in meiosis, hybrids between Res1 and Res2 were constructed and their functions analysed. The results indicate an absolute requirement for the Res2 C-terminus for normal meiosis to occur whereas the origin of the DNA-binding region is irrelevant. The implications of these results for the regulation of the MCB-binding complexes will be discussed.
Cell Cycle Proteins↗
The first day in blue.
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Adaptation, Psychological↗
Rapamycin dissociates p70(S6K) activation from DNA synthesis stimulated by bombesin and insulin in Swiss 3T3 cells.
Phosphorylation and subsequent activation of p70 S6 kinase (S6K) are events that are highly conserved in the cellular response to mitogens. The neuropeptide bombesin, which is a potent mitogen for Swiss 3T3 cells, stimulated a time- and dose-dependent activation of p70(S6K) as determined by gel mobility shift and immune complex kinase assays. This effect was inhibited by the immunosuppressant rapamycin at 10 nM, which also completely abolished bombesin-stimulated DNA synthesis at identical concentrations. In striking contrast, the combination of bombesin and insulin in synergy stimulated maximum DNA synthesis in these cells despite persistent inhibition of p70(S6K) by rapamycin throughout G1. These results indicate that activation of p70(S6K) is not required for the transition of quiescent cells to the S phase of the cell cycle. The inhibitory effects of rapamycin on bombesin-stimulated cell cycle progression did not involve accumulation of the cyclin-dependent kinase inhibitor p27(kip1) but a striking inhibition of the expression of cyclin D1. This effect was circumvented by bombesin with insulin, suggesting that a rapamycin-insensitive pathway stimulated by this combination leads to cyclin D1 expression. Thus, these findings, dissociating the mitogenic effects of bombesin in synergy with insulin from activation of p70(S6K), support the hypothesis that this kinase is a component of one of the parallel pathways that can lead to DNA synthesis rather than an obligatory point of convergence in mitogenic signaling.
3T3 Cells↗
Type II myosin involved in cytokinesis in the fission yeast, Schizosaccharomyces pombe.
We have cloned an unique gene encoding the heavy chain of a type II myosin in the fission yeast, Schizosaccharomyces pombe. The myo2+ gene encodes a protein of 1526 amino acids with a predicted molecular weight of 177 kDa and containing consensus binding motifs for both essential and regulatory light chains. The S. pombe myo2+ head domain is 45% identical to myosin IIs from Saccharomyces cerevisiae and Homo sapiens and 40% identical to Drosophila melanogaster Structurally, myo2+ most closely resembles budding yeast MYO1, the tails of both myosin IIs containing a number of proline residues that are predicted to substantially disrupt the ability of these myosins to form coiled coils. The myo2+ gene is located on chromosome III, 8.3 map units from ade6+. Deletion of approximately 70% of the coding sequence of myo2+ is lethal but myo2delta spores can acquire a suppressor mutation that allows them to form viable microcolonies consisting of filaments of branched cells with aberrant septa. Overexpression of myo2+ results in the inhibition of cytokinesis; cells become elongated and multinucleate and fail to assemble a functional cytokinetic actin ring and are either aseptate or form aberrant septa. These results suggest that a contractile actin-myosin based cytokinetic mechanism appeared early in the evolution of eukaryotic cells and further emphasise the utility of fission yeast as a model organism in which to study the molecular and cellular basis of cytokinesis.
Amino Acid Sequence↗
Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.
The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age (P<0.01), anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l, P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).
Adult↗
Metabolic disposition of [14C]-trimethylamine N-oxide in rat: variation with dose and route of administration.
1. Urine was the major route of excretion of radioactivity (95% dose in 0-24 h) following the oral, intravenous or intraperitoneal administration of [14C]-trimethylamine N-oxide dihydrate (1 mmol/kg body wt) to the adult male Wistar rat. A further 3-4% was voided in the urine during 24-72 h. Only fractional amounts were detected in the faeces, or were retained within tissues 3 days after administration. 2. Biliary secretion of radioactivity was insignificant (0.18% in 0-4 h) but larger amounts were secreted directly into the lumen of the gastrointestinal tract, especially the small intestine (2.6% in 0-1 h). 3. The only radioactive compounds identified in the urine were trimethylamine N-oxide and dimethylamine. Larger amounts of dimethylamine were excreted following oral administration (10%) as opposed to intravenous (2.5%) or intraperitoneal (1.5%) input. This production of dimethylamine occurred over a 100-fold oral trimethylamine N-oxide dose range (0.3-30 mmol/kg body wt). Incubation of trimethylamine N-oxide with gut contents (especially colon and rectum) led to the formation of dimethylamine.
Administration, Oral↗
Streptococcus pneumoniae blood culture isolates from patients with and without human immunodeficiency virus infection: alterations in penicillin susceptibilities and in serogroups or serotypes.
We performed a 3-year retrospective study of Streptococcus pneumoniae blood culture isolates recovered at Baragwanath Hospital, Soweto, South Africa, from 1993 to 1995. The study group comprised 457 patients, including 98 children, of known human immunodeficiency virus (HIV) serostatus. Of these patients, 70 (30 [8.4%] of 359 adults and 40 [40.8%] of the 98 children) were infected with penicillin-resistant S. pneumoniae strains (minimal inhibitory concentration, > or = 0.12 microg/mL); 56 of these strains were intermediately resistant to penicillin. HIV-positive patients had significantly more penicillin-resistant isolates than did HIV-negative patients (43 [29.7%] of 145 HIV-positive patients vs. 27 [8.6%] of 312 HIV-negative patients; P < .001); this difference was found for both adults (19% vs. 4.3%; P < .001) and children (53.3% vs. 30.2%; P < .0343). Multiple resistance occurred more frequently in HIV-positive children (P = .02). HIV-positive adults had a statistically significant increase in the percentage of serogroups and serotype usually found in children and commonly associated with antimicrobial resistance, i.e., serotype 14 and serogroups 6, 19, and 23 (48% vs. 28.6%; P < .001). The increased prevalence of serogroups or serotypes usually found in children was also found among penicillin-susceptible strains. These data suggest that HIV-infected adults may again become susceptible to the serogroups or serotypes found in children.
AIDS-Related Opportunistic Infections↗
Axonal injury in falls.
Amyloid precursor protein (APP) immunocytochemistry was used as a marker for axonal injury (AI) in a series of 16 cases of head trauma associated with fatal falls. Nine cases were falls from not more than the person's own height (falls from < or = own height) and seven cases were falls from a distance greater than the person's own height (falls from > own height). AI was recorded on a series of line diagrams of standard brain sections divided into 116 sectors. AI around focal lesions (infarcts, hemorrhages, contusions) was distinguished from nonfocal axonal injury that was distant from any focal area of damage. The percentage of sectors showing focal AI provided the Focal Axonal Injury Score (FAIS) and the percentage showing nonfocal AI the Non-Focal Axonal Injury Score (NFAIS). The FAIS is a measure of secondary AI and the NFAIS of diffuse axonal injury (DAI). The percentage of sectors involved with AI (focal and nonfocal) provided the cumulative Axonal Injury Score (AIS). A semiquantitative grading system was also used to assess the severity of axonal injury in each sector and the sum of the grades from all sectors was expressed as a percentage to provide the Axonal Injury Severity Score (AISS). Widespread AI was present in all cases irrespective of the height of the fall. AI was present in the midbrain (94%), pons (94%), corpus callosum (100%), central grey matter (100%), and cerebral hemispheric white matter (94%). AIS ranged from 10 to 94 in falls from < or = own height (mean 73) and from 38 to 92 in falls from > own height (mean 82). AISS ranged from 6 to 95 in falls from < or = own height (mean 65) and 28 to 95 in falls from > own height (mean 72). There was no statistically significant difference in AIS or AISS between the two groups. The extent and severity of AI cannot be predicted from biomechanical data, such as the height of the fall, as the total AI in a given case is a variable mixture of Nonfocal AI (DAI) and Focal AI arising by secondary mechanisms, and APP immunostaining is unable to distinguish primary from secondary AI. However, the combination of the Hypoxic-Ischemic Score (HIS) defined as the percentage of sectors showing any hypoxic-ischemic damage ranging from neuronal "red cell change" to infarction in conjunction with the FAIS and NFAIS provided a measure of the relative contribution of primary and secondary AI in a given brain.
Accidental Falls↗
Erysipelothrix rhusiopathiae septicemia in a neonate.
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Bacteremia↗
Rheumatic manifestations of inherited diseases.
In this paper the rheumatic features of a selection of inherited diseases are reviewed. Further evidence has been reported strengthening the association between hypercholesterolemia and Achilles tendinous xanthomatosis, although the clinical manifestations of hyperlipidemic arthropathy remain poorly understood. Osteonecrosis of the femoral head is demonstrated to have a good functional prognosis in children and adolescents with Gaucher's disease. Magnetic resonance imaging of the liver may prove to be useful in monitoring enzyme replacement in Gaucher's disease because it correlates with the presence of avascular necrosis. A case of cervical myelopathy in Hunter's disease is also presented.
Genetic Diseases, Inborn↗