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Biomedical subjects

R Carter

Publications and source records attributed to R Carter.

At least 91 records · Page 5Linked to original sources

Amplification of the t(2; 13) and t(1; 13) translocations of alveolar rhabdomyosarcoma in small formalin-fixed biopsies using a modified reverse transcriptase polymerase chain reaction.

Detection of characteristic chromosomal translocations has aided diagnosis of the small round cell tumors of childhood and may help to stratify patients into clinical groups. The detection of the abnormalities by classical cytogenetic techniques has been supplemented by fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). These techniques allow diagnoses to be made using only very small amounts of tumor tissue. We here describe a technique for the rapid and specific detection by modified reverse transcriptase polymerase chain reaction of characteristic chromosomal translocations of alveolar rhabdomyosarcoma with small amounts of formalin-fixed tissue as the starting material. Of 27 samples studied, 4 cases are described in which the detection of translocations by this method cast doubt on the original histopathological diagnosis. These cases demonstrate the critical diagnostic importance of the detection of these translocations in rhabdomyosarcoma.

Adolescent↗

A MAP kinase homologue from the human malaria parasite, Plasmodium falciparum.

Pfmap-1, a gene encoding a novel protein kinase, has been identified in the human malaria parasite Plasmodium falciparum, using the polymerase chain reaction with degenerate oligodeoxyribonucleotides designed to hybridise to conserved regions of cdc2-related kinases. Computer comparison with other protein kinases strongly suggests that the protein encoded by this gene is closely related to mitogen-activated protein (MAP) kinases, which play important roles in eukaryotic adaptative response and signal transduction. In addition to the conserved MAP kinase catalytic domain, Pfmap-1 contains a highly charged C-terminal extension that includes two sets of repeated amino acid motifs. Pfmap-1 is located on chromosome 14 of P.falciparum, and its mRNA has a size of 3.7 kb.

Amino Acid Sequence↗

Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors.

The mammalian form of the protozoan parasite Leishmania mexicana contains high activity of a cysteine proteinase (LmCPb) encoded on a tandem array of 19 genes (lmcpb). Homozygous null mutants for lmcpb have been produced by targeted gene disruption. All life-cycle stages of the mutant can be cultured in vitro, demonstrating that the gene is not essential for growth or differentiation of the parasite. However, the mutant exhibits a marked phenotype affecting virulence-- its infectivity to macrophages is reduced by 80%. The mutants are as efficient as wild-type parasites in invading macrophages but they only survive in a small proportion of the cells. However, those parasites that successfully infect these macrophages grow normally. Despite their reduced virulence, the mutants are still able to produce subcutaneous lesions in mice, albeit at a slower rate than wild-type parasites. The product of a single copy of lmcpb re-expressed in the null mutant was enzymatically active and restored infectivity toward macrophages to wild-type levels. Double null mutants created for lmcpb and lmcpa (another cathepsin L-like cysteine proteinase) have a similar phenotype to the lmcpb null mutant, showing that LmCPa does not compensate for the loss of LmCPb.

Animals↗

Anton P. Chekhov, MD (1860-1904): dual medical and literary careers.

This is a story of a physician who was one of the world's greatest short story writers. Anton Pavlovich Chekhov successfully performed dual careers of writing and practicing medicine during a short but productive life. Many biographers overlook Dr Chekhov's role, although his medical training and practice flowed over into his writing, influencing both his subject matter and his style. His stories and plays reveal the insights that Dr Chekhov discovered about the human psyche at work, thus delving into psychosomatic medicine nearly 50 years before its time. Despite orders to stop practicing medicine because of his own deteriorating health, Chekhov devoted himself further to the study of medicine, publishing a landmark study in social medicine that advocated reform of the Russian penal system. Meanwhile, his fictional works earned him the coveted Pushkin prize for the best literary work of the year in 1888. Shortly after celebrating his third wedding anniversary to actress Olga Knipper, Anton Chekhov died at age 44, victim of a nearly lifelong battle with tuberculosis.

Famous Persons↗

Respiratory dysfunction and white cell activation following cardiopulmonary bypass: comparison of membrane and bubble oxygenators.

OBJECTIVE: Cardiopulmonary bypass induces respiratory dysfunction postoperatively, with activation of both the complement system and white cells implicated. This study compared the effects of bubble and membrane oxygenators for cardiopulmonary bypass in terms of respiratory dysfunction and markers of white cell activation and endothelial damage. METHODS: Fifty patients undergoing cardiopulmonary bypass were randomly allocated either membrane or bubble oxygenation. Respiratory function was assessed serially by arterial oxygen tension and alveolar-arterial oxygen gradient. Complement activation was measured by serial sampling of serum C3a levels. White cell activation was assessed by serial measurement granulocyte elastase; other markers investigated were levels of thromboxane B2, von Willebrand factor and malondialdehyde. All sample measurements were made preoperatively, early and late during bypass, 4-6 h postoperatively and then on the 1st, 2nd and 6th postoperative day. All samples were corrected for haemodilution, and differences between groups tested non-parametrically. RESULTS: In both groups of patients there was a highly significant fall (P < 0.001) in arterial oxygen tension accompanied by a highly significant rise (P < 0.0001) in aleveolar-arterial oxygen gradient at 18 h compared to preoperative values persisting until 6 days postoperatively. Levels of C3a increased significantly in both groups at 10 min post bypass, increased further at 60 min peaking at 4-6 h post bypass. Granulocyte elastase serum levels increased significantly at 10 min postoperatively in both groups compared to control levels, remaining elevated till 48 h, but returning to control levels by 6 days. There was a small difference (P < 0.04) between the groups at 4-6 h only. Levels of von Willebrand factor increased significantly at 60 min post bypass in both groups, remaining elevated 6 days postoperatively. Levels of malondialdehyde increased at 10 min post bypass, remaining elevated until 6 days post bypass. Thromboxane levels showed no significant changes. For all markers measured, there were no significant differences between the groups other than those already indicated. CONCLUSIONS: This study demonstrated marked respiratory dysfunction, complement activation and white cell activation in patients undergoing cardiopulmonary bypass with either bubble or membrane oxygenators. There was marked variability in the response of individual patients with either oxygenation technique, but overall no significant differences between the groups.

Blood Gas Analysis↗

Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families.

The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families. We screened 49 site-specific breast cancer families for mutations in the BRCA2 gene using single strand conformation analysis (SSCA) followed by direct sequencing. We found mutations in eight families, including all four families with male breast cancer. The eight mutations were small deletions with the exception of a single nonsense mutation, an all were predicted to interrupt the BRCA2 coding sequence and to lead to a truncated protein product. Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03). Two mutations were seen twice, including a 8535delAG, which was detected in two French Canadian families. Our results suggest the possibility that the proportion of site-specific breast cancer families attributable to BRCA2 may be overestimated.

Adult↗

A malaria parasite toxin associated with Plasmodium vivax paroxysms.

We have previously demonstrated a correlation between clinical paroxysms in Plasmodium vivax malarial infections and the appearance in patients' plasma of factors that kill blood stage parasites (gametocytes). This activity was, as previously shown, dependent on the presence in paroxysm plasma of tumour necrosis factor-alpha (TNF-alpha), which acts in conjunction with other 'complementary' factors. Here we have identified a parasite component which is essential for this activity and functions as a 'complementary' factor together with TNF, and a third component of unknown origin. The P. vivax parasite component present in paroxysm plasma can be substituted with a blood-stage schizont extract of either P. vivax or P. falciparum. This was demonstrated by restoring the parasite-killing activity to post-paroxysm plasma (from which it was absent) with the addition of the extracts together with TNF. The active materials in these extracts, however, are different from the natural components in P. vivax paroxysm plasma, i.e. while the schizont extracts are immunologically cross-reactive between species, the activity of the natural P. vivax toxin(s) in patients' plasma is neutralized only by the homologous antisera. Plasmodium falciparum infections have neither distinct paroxysms nor parasite-killing activity in plasma. The pronounced paroxysms of P. vivax infections may thus be due in part of a species-specific toxin(s).

Acute Disease↗

Past quit smoking assistance and doctors' advice for white and African-American smokers.

Data for 473 African-American and white smokers showed that whites were more likely than African Americans to use formal cessation programs to quit smoking, to report that their doctor told them to stop smoking, and to use nicotine replacement therapy. While physicians advised a high proportion of smokers of each race group to quit smoking and were quite aggressive in prescribing nicotine replacement therapy, they were deficient in providing necessary behavioral support to their patients.

Adult↗

A prospective study of six methods for detection of hepatic colorectal metastases.

Many techniques are available for the identification of patients with hepatic colorectal metastases. The accuracy and clinical relevance of transabdominal ultrasound (US), computed tomography (CT), static scintigraphy, dynamic scintigraphy (HPI), intraoperative ultrasound (IOUS) and manual palpation, in the detection of intrahepatic colorectal metastases were assessed in 73 consecutive patients presenting with colorectal carcinoma; 39 were male and 34 female with a mean age of 68 years (range 43-90 years). In 33 patients either intraoperative ultrasound or palpation were omitted owing to emergency presentation (n = 14) or subsequent non-operative management (n = 19). All six investigations were completed in 40 patients. Computed tomography and hepatic perfusion scintigraphy (HPI) were the most sensitive, detecting over 90% of lesions, the others identifying approximately 80% of lesions, Specificity in all methods, apart from dynamic scintigraphy, was over 80%. Contrast-enhanced CT would appear to remain the most accurate method available. However, if the prognostic ability of HPI is confirmed on subsequent follow-up, the accuracy of HPI will rise with time, whereas that of CT will fall. Intraoperative ultrasonography took time to perform and did not alter the management of any patient within the study. We suggest that its use is limited to those patients in whom resection is contemplated, where the vascular anatomical detail provided may be invaluable.

Adult↗

Write it now, or never!

Writers need knowledge and credentials to write, but one key to successful writing is to start writing now. Often the only difference between a published writer and a unpublished writer is simply that the published writer did the writing.

Denial, Psychological↗

Spontaneous regression in angiocentric T-cell lymphoma.

An 8-year-old boy presented with a 10-week history of ulcerating lesions which were histologically and immunocytochemically consistent with the diagnosis of angiocentric T-cell lymphoma. The disease was limited to the skin and resolved with no chemotherapy. Angiocentric T-cell lymphoma is commonly a disease with considerable morbidity and is often fatal. Epstein-Barr virus (EBV) could not be identified in involved tissue by immunostaining or by in situ hybridization. We consider whether the uncharacteristic absence of EBV in this case has prognostic significance.

Child↗

The influence of fat free mass on prediction of densitometric body composition by bioelectrical impedance analysis and by anthropometry.

OBJECTIVE: To examine the effect of varying size of fat free mass (FFM) on the precision and bias of body composition prediction by bioelectrical impedance analysis (BIA) from four equations of Segal et al (BIA-Segal), Gray et al (BIA-Gray, Lukaski et al (BIA-Lukaski) and those from a manufacturer (BIA-EZC), by body mass index (BMI), and by skinfold methods with reference to estimation by densitometry. SUBJECTS: 73 men and 77 women aged 17-71 years, were measured for height, weight, FFM, bioelectrical impedance and age. RESULTS: BIA-Segal gave the highest precision (men: R2 = 83%, women: R2 = 75%) and the least bias (men: slope = 0.88; women: slope = 0.81) of all BIA methods. There were poorer precision (R2 < or = 50%) and more bias (slope < 0.70) by BIA-Lukaski and BIA-EZC in both sexes, which were comparable to the simpler BMI method. The skinfold method gave R2 = 83% and slope = 0.84 in men and R2 = 61% and slope = 0.86 in women. Bland and Altman analysis showed BIA-Segal gave prediction of FFM within +/-6 kg of 95% confidence interval limit of agreement of that estimated by UWW in most subjects. Other BIA methods presented unacceptably large underestimates of up to 15-17 kg in FFM. CONCLUSIONS: The BIA-Segal provide the best predictions of the methods tested, but using BMI-or waist-specific equations may be more practical than the original BIA-Segal method, which BIA methods are affected by large FFM, and not better than anthropometric methods in predicting FFM.

Adolescent↗

Tour de force.

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Cell Division↗