Gastric leiomyosarcoma presenting as severe iron-deficiency anaemia.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C Mitchell
Publications and source records attributed to C Mitchell.
Risk factors for hepatitis C transmission in the Victorian population: a telephone survey.
OBJECTIVE: To measure knowledge and prevalences of risk factors for hepatitis C infection in the Victorian community. METHOD: Telephone survey of 757 Victorian householders aged 15+ years, March 1996. RESULTS: An estimated 2.2% of Victorians have injected illicit drugs; 4.8% have tattoos and 49.6% have skin piercings; 11.4% received a blood transfusion before screening for HCV was introduced; 10.9% have had a test for HCV antibody. A majority of respondents perceived sexual contact and receipt of a transfusion to be risks for HCV transmission. CONCLUSIONS: Risk factors associated with the spread of HCV are widespread in the Victorian community; however, the most important risk factor--injecting drug use--has low prevalence. Considerable uncertainty exists about risk factors for hepatitis C. IMPLICATIONS: A very small percentage of Victorians are injecting drug users and therefore at highest risk of hepatitis C infection, therefore transmission control programs can be efficiently focused on this group. The Victorian community needs to be better educated about risk factors for hepatitis C, in particular that transfusions and blood donations are safe.
Adolescent↗
Vasopressin increases Na-K-2Cl cotransporter expression in thick ascending limb of Henle's loop.
To investigate whether the enhancement of thick ascending limb (TAL) NaCl transport in response to long-term increases in circulating vasopressin concentration is associated with increased expression levels of the apical Na-K-2Cl cotransporter in the rat TAL, we have carried out immunoblotting and immunofluorescence studies using affinity-purified, peptide-directed antibodies. Semiquantitative immunoblotting studies demonstrated a marked increase (193% of controls) in Na-K-2Cl cotransporter band density in response to restriction of water intake to 15 ml/day for 7 days. In contrast, the expression levels of two other apical proteins of the TAL (the type 3 Na/H exchanger and Tamm-Horsfall protein) were unchanged in the outer medulla. A 7-day subcutaneous infusion of the V2 receptor-selective vasopressin analog, 1-desamino-[8-D-arginine]vasopressin (DDAVP), to Brattleboro rats also markedly increased Na-K-2Cl cotransporter expression in the outer medulla (183% of controls). Immunofluorescence localization in outer medullary tissue sections confirmed the increase in Na-K-2Cl cotransporter expression in response to DDAVP. We conclude that vasopressin strongly upregulates the expression of the Na-K-2Cl cotransporter of the TAL and that it is likely to play an important role in the long-term regulation of the countercurrent multiplication system.
Animals↗
Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney.
Aldosterone stimulates sodium transport in the renal collecting duct by activating the epithelial sodium channel (ENaC). To investigate the basis of this effect, we have developed a novel set of rabbit polyclonal antibodies to the 3 subunits of ENaC and have determined the abundance and distribution of ENaC subunits in the principal cells of the rat renal collecting duct. Elevated circulating aldosterone (due to either dietary NaCl restriction or aldosterone infusion) markedly increased the abundance of alphaENaC protein without increasing the abundance of the beta and gamma subunits. Thus, alphaENaC is selectively induced by aldosterone. In addition, immunofluorescence immunolocalization showed a striking redistribution in ENaC labeling to the apical region of the collecting duct principal cells. Finally, aldosterone induced a shift in molecular weight of gammaENaC from 85 kDa to 70 kDa, consistent with physiological proteolytic clipping of the extracellular loop as postulated previously. Thus, at the protein level, the response of ENaC to aldosterone stimulation is heterogenous, with both quantitative and qualitative changes that can explain observed increases in ENaC-mediated sodium transport.
Aldosterone↗
Expression of heat shock protein 70 in leukocytes of patients with sepsis.
The heat shock proteins are known to protect cells against diverse injuries such as cytotoxicity by TNFalpha acting mainly as chaperones for denatured proteins. Lipopolysaccharide stimulates the production and the release of numerous endogenous mediators of sepsis: tumor necrosis factor alpha, interleukin-1, and interleukin-6 that induce fever production. Moreover, temperature at 40 degrees C is sufficient to induce heat shock and attenuate both TNFalpha and IL-1 expression. We demonstrate a distinct profile in gene expression of HSP 70 family in leukocytes obtained from different phases of septic patients. Our findings strongly suggest that HSP 70 may play a role in the outcome of septic shock patients.
Adult↗
Imaging of patients with Wilms' tumor.
Continued advances in imaging technology have improved the ability to detect Wilms' tumor and its precursor, nephroblastomatosis, as well as tumor spread to other organs in a less invasive manner than in years past. However, there is still wide variation in clinical practice in the imaging of this tumor compared with the guidelines set forth by the National Wilms' Tumor Study Group. This article reviews current imaging options and recommendations for the evaluation of children with Wilms' tumor as well as for surveillance of children with associated disorders such as hemihypertrophy.
Child, Preschool↗
The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein.
Although the collecting duct is regarded as the primary site at which mineralocorticoids regulate renal sodium transport in the kidney, recent evidence points to the distal convoluted tubule as a possible site of mineralocorticoid action. To investigate whether mineralocorticoids regulate the expression of the thiazide-sensitive Na-Cl cotransporter (TSC), the chief apical sodium entry pathway of distal convoluted tubule cells, we prepared an affinity-purified, peptide-directed antibody to TSC. On immunoblots, the antibody recognized a prominent 165-kDa band in membrane fractions from the renal cortex but not from the renal medulla. Immunofluorescence immunocytochemistry showed TSC labeling only in distal convoluted tubule cells. Semiquantitative immunoblotting studies demonstrated a large increase in TSC expression in the renal cortex of rats on a low-NaCl diet (207 +/- 21% of control diet). Immunofluorescence localization in tissue sections confirmed the strong increase in TSC expression. Treatment of rats for 10 days with a continuous subcutaneous infusion of aldosterone also increased TSC expression (380 +/- 58% of controls). Furthermore, 7-day treatment of rats with an orally administered mineralocorticoid, fludrocortisone, increased TSC expression (656 +/- 114% of controls). We conclude that the distal convoluted tubule is an important site of action of the mineralocorticoid aldosterone, which strongly up-regulates the expression of TSC.
Aldosterone↗
Management of deliberate self poisoning. Liaison psychiatric nurses can be used to increase psychosocial assessments.
Explore the source record for details and available documents.
Hospitalization↗
Biologically-generated primer for PCR: PCR primer of unknown sequence.
We describe a method for producing specific PCR primers directly from PCR product, bypassing the usual need to know the primer sequence. Lack of abundance of primers derived from a PCR product is compensated for by the incorporation of an arbitrary 5'TAG sequence which acts as a surrogate template target for the bulk amplification phase. We use the technique to amplify clonospecific rearranged immunoglobulin genes, which have applications as markers of lymphoid neoplasms for tracing the success of therapy. The principle may have wider application wherever conserved and variable regions of DNA are juxtaposed.
Base Sequence↗
Temporal dynamics of corticosterone elevation in successive negative contrast.
A negative contrast effect in consummatory behavior that occurred when rats were shifted from 32% to 4% sucrose was accompanied by elevations in corticosterone that were measurable at 10 and 20 min but not at 40 min after the second postshift day. No corticosterone elevations were found to accompany contrast at 10 or 15 min after the first postshift day in these experiments nor immediately after the first postshift day in an earlier experiment. The present study also found an anticipatory elevation in plasma corticosterone in shifted animals just before their placement in the apparatus on the second postshift day. These results are discussed in terms of a multistage hypothesis of successive negative contrast. The anticipatory elevation is discussed in terms of uncontrollability and unpredictability of aversive events.
Animals↗
A study of females with deletions of the short arm of the X chromosome.
We have undertaken a clinical and molecular study of 25 females with deletions of the short arm of the X chromosome. We have determined the deletion breakpoints, the parental origin and the activation status of the deleted X chromosomes. Genotype-phenotype correlations suggest that the presence of a single copy of the DFFRX gene, previously postulated as a gene involved in the ovarian failure seen in Turner syndrome, may be compatible with normal ovarian function, and that there may be a gene for Turner-like features located in distal Xp22.3.
Adolescent↗
A clinical, cytogenetic and molecular study of ten probands with supernumerary inv dup (15) marker chromosomes.
Ten probands with moderate to severe developmental delay were found to have a supernumerary inv dup (15) chromosome. These patients and their families were studied by both cytogenetic and molecular methods. Cytogenetic polymorphisms associated with the 15p short arm suggested a maternal derivation for the marker chromosome in all informative cases. One marker was directly maternally inherited. Molecular analysis employing Southern blotting and polymerase chain reaction (PCR) of microsatellite repeats demonstrated the presence of extra alleles in the 15q11q13 region. All ten of the probands demonstrated an extra band at one or more locus without recourse to densitometry. All of the inv dup (15) markers were comparable in size to a G group chromosome but there were differences in the positions of the breakpoints in 15q. There was an inconsistent relationship between marker size, gene dosage and severity of phenotype.
Adolescent↗
Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes.
Hepatocyte transplantation might represent a potential therapeutic alternative to liver transplantation in the future; however, transplanted cells have a limited capacity to repopulate the liver, as they do not proliferate under normal conditions. Recently, studies in urokinase (uPA) transgenic mice and in fumarylacetoacetate hydrolase (FAH)-deficient mice have shown that the liver can be repopulated by genetically engineered hepatocytes harboring a selective advantage over resident hepatocytes. We have reported that transgenic mice expressing human Bcl-2 in their hepatocytes are protected from Fas/CD95-mediated liver apoptosis. We now show that Bcl-2 transplanted hepatocytes selectively repopulate the liver of mice treated with nonlethal doses of the anti-Fas antibody Jo2. FK 506 immunosuppressed mice were transplanted by splenic injection with Bcl-2 hepatocytes. The livers of female recipients were repopulated by male Bcl-2 transgenic hepatocytes, as much as 16%, after 8 to 12 administrations of Jo2. This only occurred after anti-Fas treatment, confirming that resistance to Fas-induced apoptosis constituted the selective advantage of these transplanted hepatocytes. Thus, we have demonstrated a method for increasing genetic reconstitution of the liver through selective repopulation with modified transgenic hepatocytes, which will allow optimization of cell and gene therapy in the liver.
Animals↗
Seroprevalence of human herpesvirus 8 among Zambian women of childbearing age without Kaposi's sarcoma (KS) and mother-child pairs with KS.
The seroprevalence of human herpesvirus 8 (HHV-8) among a group of Zambian women of reproductive age and among mother-child pairs in which either one of them has Kaposi's sarcoma (KS) was determined. A cross-sectional group of 378 pregnant women was randomly recruited into the study, and 183 (48.4%) had HHV-8 antibodies. Among the human immunodeficiency virus (HIV)-1-infected women, 51.1% were HHV-8-seropositive, whereas of HIV-1-negative women, 47.3% were HHV-8-seropositive. In addition, 21 women index patients with KS and 5 young children index patients with KS were studied. All children with KS had mothers who were HHV-8-seropositive, while not all children whose mothers had KS were infected with HHV-8. Our study suggests that there is a high HHV-8 seroprevalence among Zambian women, and the rate is almost the same in HIV-1-positive and -negative women. This high seroprevalence may be a contributing factor toward the increased frequency of KS in this population.
Adolescent↗
Carbohydrate deficient transferrin in detecting relapse in alcohol dependence.
Patients reports together with findings at clinical examination and information from an informant such as a relative were used to categorise patients as relapsed or not relapsed during a 6 month period of out-patient treatment at an alcohol problems clinic. At each fortnightly visit, blood was taken for measurement of serum gamma-glutamyl transferase and carbohydrate deficient transferrin (Pharmacia method). A total of 53 patients attended for at least one follow-up visit. Mean CDT differentiated relapsers from non-relapsers at seven of the 11 visits (P < 0.05), but at no visit did mean GGT differentiate. CDT tended to become elevated after a relapse more quickly than GGT. However, whether using upper limit of normal (ULN), or defining a 'positive test' as > last test and either > 20% above lowest previous test or > ULN, specificity (averaged over the 11 visits) was greater for GGT than CDT. Some of the false positive results for CDT were in patients who, shortly after having a positive test, relapsed, suggesting that a rising CDT can herald a relapse admitted by the patient. This could not be shown for false positive GGT results. Inspection of individual trajectories of alcohol consumption and blood test results shows that for some patients GGT is the more effective marker of relapse, whilst for others CDT operates better.
Adult↗
A molecular and FISH approach to determining karyotype and phenotype correlations in six patients with supernumerary marker(22) chromosomes.
In a cytogenetic, molecular, and clinical study of patients with autosomal supernumerary marker chromosomes (SMC), 6 out of 72 (8.3%) were shown by fluorescence in situ hybridisation (FISH) to be derived from chromosome 22. PCR microsatellite analysis and FISH using primers and cosmids from proximal 22q showed 3 of the 6 to contain euchromatin. The first, a de novo nonmosaic bisatellited, dicentric SMC, was acsertained in a patient with cat eye syndrome and Duane anomaly. Microsatellite analysis showed the SMC was maternal in origin with euchromatin extending to D22S427, i.e., proximal to the DiGeorge syndrome critical region (DGSCR). The second, a nonmosaic bisatellited, dicentric marker, was found in a child with severe hypotonia and developmental delay and had been inherited from the patient's phenotypically normal father. FISH showed the SMC to contain euchromatin extending into the DGSCR. The third, a de novo SMC, was ascertained antenatally and was shown to contain 22q euchromatin extending distal to the DGSCR. The 19-week terminated fetus was phenotypically normal at autopsy. Two of the three SMC(22)s not containing detectable proximal 22q euchromatin were ascertained coincidentally in phenotypically normal individuals, whereas the third, the only mosaic with a minority euploid cell line, was found in a patient with mild developmental delay. These results suggest that SMC(22)s devoid of proximal 22q euchromatin are not associated with adverse phenotypic effects whereas SMC(22)s containing euchromatin may be found in individuals with phenotypes ranging from cat eye syndrome to normal.
Chromosome Aberrations↗
The nucleotidylylation of herpes simplex virus 1 regulatory protein alpha22 by human casein kinase II.
The products of the alpha genes of herpes simplex virus 1, the infected cells proteins (ICP) 0, 4, 22, and 27 perform regulatory functions, are nucleotidylylated, and share the signaling or recognition sequence (RR(A/T)(P/S)R) that correctly predicted the nucleotidylylation of viral proteins encoded by UL21, UL31, UL49, and UL47 genes expressed later in infection. Extracts from uninfected HeLa cells or casein kinase II purified from sea star nucleotidylylated the ICP22 moiety of a glutathione S-transferase-ICP22 (GST22P) fusion protein with [alpha-32P]ATP or [2-3H]ATP. We report that: (i) Purified HeLa cell casein kinase II specifically labeled a glutathione S-transferase fusion protein containing the amino-terminal 151 amino acids of ICP22 with [2-3H]ATP. (ii) Nucleotidylylation of GST-ICP22 by purified enzyme exhibited positive cooperativity (Hill coefficient of 2 and a K' of 3.7 microM) and a Km = 37.7 microM for ATP. (iii) Nucleotidylylation was inhibited by heparin, casein, or ATPalphaS but not by ATPgammaS. (iv) Mutation of the signaling sequence from RRAPRR to LKAPEK abolished nucleotidylylation. We conclude that nucleotidylylation of proteins by casein kinase II requires the presence of the signaling or recognition sequence, involves the cleavage of the phosphodiester bond between the alpha and beta phosphate, and need not be preceded by phosphorylation.
Adenosine Triphosphate↗
A 50 kilodalton protein associated with raf and pp60(v-src) protein kinases is a mammalian homolog of the cell cycle control protein cdc37.
Several oncogenic protein kinases including c-raf-1 and pp60(v-src) are known to directly interact with the 90 kDa heat shock protein (hsp90)/p50 complexes. Using a monoclonal antibody to detect p50 during a purification scheme, p50 was purified to homogeneity. Internal amino acid sequence information was obtained and used to clone a partial cDNA. Comparison of the p50 sequence to other cloned proteins revealed 89% homology with a glycosaminoglycan-binding protein and 54% homology with Drosophila cell cycle control protein (cdc) 37. Monoclonal and polyclonal antibodies were produced against a cleaved fusion protein that recognizes p50 with a high level of specificity. These antibodies recognize the 50 kDa protein present in c-raf-1 and pp60(v-src) complexes. No other proteins were recognized with these antibodies suggesting that p50 is a unique protein. Immunocytochemical visualization of p50 in NIH 3T3 cells indicates a primarily cytoplasmic localization around the nuclear membrane. A survey of p50 expression in murine tissues on a protein blot revealed the following relative levels of expression; thymus > spleen > brain > heart > kidney > liver > lung > skeletal muscle. These results link studies demonstrating complexation of certain kinases with hsp90/p50 in mammalian cells and a number of reports in yeast and Drosophila, demonstrating the importance of cdc37 in cell cycle and kinase function.
3T3 Cells↗