Effects of losartan in patients with a systemically functioning morphologic right ventricle after atrial repair of transposition of the great arteries.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
E Ryan
Publications and source records attributed to E Ryan.
Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.
Salmonella enterica subspecies I, serovar Typhimurium (S. typhimurium), is a leading cause of human gastroenteritis, and is used as a mouse model of human typhoid fever. The incidence of non-typhoid salmonellosis is increasing worldwide, causing millions of infections and many deaths in the human population each year. Here we sequenced the 4,857-kilobase (kb) chromosome and 94-kb virulence plasmid of S. typhimurium strain LT2. The distribution of close homologues of S. typhimurium LT2 genes in eight related enterobacteria was determined using previously completed genomes of three related bacteria, sample sequencing of both S. enterica serovar Paratyphi A (S. paratyphi A) and Klebsiella pneumoniae, and hybridization of three unsequenced genomes to a microarray of S. typhimurium LT2 genes. Lateral transfer of genes is frequent, with 11% of the S. typhimurium LT2 genes missing from S. enterica serovar Typhi (S. typhi), and 29% missing from Escherichia coli K12. The 352 gene homologues of S. typhimurium LT2 confined to subspecies I of S. enterica-containing most mammalian and bird pathogens-are useful for studies of epidemiology, host specificity and pathogenesis. Most of these homologues were previously unknown, and 50 may be exported to the periplasm or outer membrane, rendering them accessible as therapeutic or vaccine targets.
Animals↗
Could fewer islet cells be transplanted in type 1 diabetes? Insulin independence should be dominant force in islet transplantation.
Explore the source record for details and available documents.
Diabetes Mellitus, Type 1↗
KOJAK encodes a cellulose synthase-like protein required for root hair cell morphogenesis in Arabidopsis.
The cell wall is an important determinant of plant cell form. Here we define a class of Arabidopsis root hair mutants with defective cell walls. Plants homozygous for kojak (kjk) mutations initiate root hairs that rupture at their tip soon after initiation. The KJK gene was isolated by positional cloning, and its identity was confirmed by the molecular complementation of the Kjk(-) phenotype and the sequence of three kjk mutant alleles. KOJAK encodes a cellulose synthase-like protein, AtCSLD3. KOJAK/AtCSLD3 is the first member of this subfamily of proteins to be shown to have a function in cell growth. Subcellular localization of the KOJAK/AtCSLD3 protein using a GFP fusion shows that KOJAK/AtCSLD3 is located on the endoplasmic reticulum, indicating that KOJAK/AtCSLD3 is required for the synthesis of a noncellulosic wall polysaccharide. Consistent with the cell specific defect in the roots of kjk mutants, KOJAK/AtCSDL3 is preferentially expressed in hair cells of the epidermis. The Kjk(-) phenotype and the pattern of KOJAK/AtCSLD3 expression suggest that this gene acts early in the process of root hair outgrowth. These results suggest that KOJAK/AtCSLD3 is involved in the biosynthesis of beta-glucan-containing polysaccharides that are required during root hair elongation.
Amino Acid Sequence↗
Bone marrow contributes to renal parenchymal turnover and regeneration.
In order to establish whether extra-renal cells contribute to the turnover and repair of renal tissues, this study examined kidneys of female mice that had received a male bone marrow transplant and kidney biopsies from male patients who had received kidney transplants from female donors. By using in situ hybridization to detect Y-chromosomes it could be demonstrated that circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells. In the human renal grafts it was confirmed that some of the recipient-derived cells within the kidney exhibited a tubular epithelial phenotype, by combining in situ hybridization with immunostaining for the epithelial markers CAM 5.2 and the lectin Ulex europaeus. Female mouse recipients of male bone marrow grafts showed co-localization of Y-chromosomes and tubular epithelial markers Ricinus communis and Lens culinaris, and a specific cytochrome P450 enzyme (CYP1A2) indicating an appropriate functional capability of clustered newly formed marrow-derived tubular epithelial cells. Y-chromosome-containing cells were observed within glomeruli, with morphology and location appropriate for podocytes. Within the murine kidney, these Y-chromosome-positive cells were negative for the mouse macrophage marker F4/80 antigen and leukocyte common antigen, but were vimentin-positive. The presence of bone marrow-derived cells was noted in both histologically normal mouse kidneys and in human transplanted kidneys suffering damage from a variety of causes. These data indicate that bone marrow cells contribute to both normal turnover of renal epithelia and regeneration after damage, and it is suggested that this could be exploited therapeutically.
Animals↗
Cell biology and genetics of root hair formation in Arabidopsis thaliana.
In this review we integrate the information available on the cell biology of root hair formation with recent findings from the analysis of root hair mutants of Arabidopsis thaliana. The mature Arabidopsis root epidermis consists of root-hair-producing cells and non-root-hair-producing cells. Root hair growth begins with a swelling of the outer epidermal wall. It has been postulated that this is due to a pH-mediated localised cell wall loosening. From the bulge a single root hair emerges which grows by tip growth. The root hair tip consists of a vesicle-rich zone and an organelle-rich subapical zone. The vesicles supply new plasma membrane and cell wall material for elongation. The cytoskeleton and its associated regulatory proteins such as profilin and spectrin are proposed to be involved in the targeting of vesicles. Ca2+ influxes and gradients are present in hair tips, but their function is still unclear. Mutants have been isolated with lesions in various parts of the root hair developmental pathway from bulge identity and initiation to control of tip diameter and extent and polarity of elongation.
Actins↗
Tumour-derived mutated K-ras codon 12 expression in regional lymph nodes of stage II colorectal cancer patients is not associated with increased risk of cancer-related death.
This study examined the frequency of lymph node micrometastases detected by expression of mutant K-ras oncogene present in the respective primary tumour. The study population consisted of consecutive patients with stage II colorectal cancer (CRC) undergoing curative resection and with disease-free survival of 60 months or longer or CRC-related death. Of 27 patients found to have K-ras mutations at codon 12, 17 had genomic DNA suitable for PCR recovered from corresponding regional lymph node tissue. The same K-ras mutation was identified in the lymph nodes of 13 patients (76%), four of whom (30%) died of CRC recurrence within 5 years. A single patient in the negative group (25%) also died. Lymph node micrometastases detected by this technique thus show no relationship to mortality in stage II CRC. Further study of this technique is necessary before it can be used in the selection of patients for adjuvant chemotherapy.
Base Sequence↗
Intrahepatic hepatitis C viral RNA status of serum polymerase chain reaction-negative individuals with histological changes on liver biopsy.
For individuals testing anti-HCV positive but negative for HCV RNA in serum, diagnosis remains unclear. Debate exists over whether these individuals have resolved infection or have similar clinical, histological, and virological profiles as serum PCR-positive individuals. The aim of this study was to assess the significance of histological changes in the liver of 33 serum PCR-negative women by investigation of clinical, histological, and intrahepatic HCV RNA status. For comparison, clinical and histological data from 100 serum PCR-positive women is presented. Viral RNA status was determined in snap-frozen liver biopsies using a sensitive nested PCR with an internal control. Although serum PCR-positive and -negative individuals shared similar age at diagnosis, source, and duration of infection, they differed from a clinical, histological, and virological perspective. Mean serum ALT levels were significantly lower in serum PCR-negative women (27.4 IU/L +/- 18 vs. 58.7 IU/L +/- 40 P <.001). Similarly, although inflammation (82%) and mild fibrosis (15%) were observed in PCR-negative biopsies, the mean HAI/fibrosis scores were significantly lower than in serum PCR-positive biopsies (1.9 +/- 1.5/0.15 +/- 0.4 vs. 4.2 +/- 1.4/1.1 +/- 1.3, respectively). Finally, HCV RNA was not detectable in serum PCR-negative liver biopsies but was detectable in all serum PCR-positive control biopsies. In conclusion, serum PCR-negative individuals may have mild histological abnormalities more suggestive of nonspecific reactive changes, steatosis or nonalcoholic steatohepatitis rather than chronic HCV, even when significant antibody responses are present in serum. Negative serum PCR status appears to reflect cleared past-exposure in liver.
Aged↗
Genetic hemochromatosis, a Celtic disease: is it now time for population screening?
In populations of northern European ancestry, hereditary hemochromatosis (HH) is tightly linked to mutations within the hemochromatosis gene (HFE gene). Over 93% of Irish HH patients are homozygous for the HFE gene C282Y mutation, providing a reliable diagnostic marker of the disease in this population. However, the prevalence of the C282Y mutation and that of the second HFE gene mutation, H63D, have yet to be determined within the Irish population. The objective of this study was to identify the true prevalence of the genetic form of HH in the Irish population. DNA was extracted from 1002 randomly selected newborn screening cards and analyzed for the C282Y and H63D mutations within the HFE gene. Complete results were obtained from 800 cards. Mutations were identified in 364 (46%) neonates. Eight (1%) neonates were homozygous for C282Y and 8 (1%) were homozygous for H63D. One hundred and fifty-five (19%) neonates were C282Y heterozygous and 226 (28%) were H63D heterozygous. Of these, 33 (4%) carried one copy of both C282Y and H63D mutations, i.e., compound heterozygous. Allele frequencies for C282Y and H63D were 11% and 15%, respectively. The high C282Y allele frequency in the Irish population together with its close linkage to HH indicate that C282Y genotyping is the preferred screening strategy for this disease in Ireland.
Ethnicity↗
The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection.
BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.
Alanine Transaminase↗
Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain.
BACKGROUND AND PURPOSE: HIV enters the CNS early in the course of infection and produces neuropsychiatric impairment throughout the course of illness, which preferentially affects the subcortical white matter. The development of a neuroimaging marker of HIV may allow for the earliest detection of cognitive impairment. The purpose of this study was to determine whether MR diffusion tensor imaging can detect white matter abnormalities in patients who have tested positive for HIV. METHODS: Ten patients with HIV (eight men and two women; mean age, 42 years) underwent MR imaging of the brain with MR diffusion tensor imaging, which included routine fluid-attenuated inversion recovery and fast spin-echo T2-weighted imaging. Diffusion constants and anisotropy indices were calculated from diffusion tensor maps. Peripheral viral load, Centers for Disease Control staging, and cluster of differentiation 4 levels were determined. RESULTS: All patients had normal results of MR imaging of the brain, except for mild atrophy. Four of 10 patients had undetectable viral loads. These patients were receiving highly active antiretroviral therapy. The diffusion constant and anisotropy were normal. Four of 10 patients had viral loads between 10,000 and 200,000. Diffusion anisotropy in the splenium and genu was significantly decreased (P < .02). The diffusion constant of the subcortical white matter was elevated in the frontal and parietooccipital lobes (11%). Two of 10 patients had viral loads >400,000. Anisotropy of the splenium was half normal (P < .0004) and of the genu was decreased 25% (P < .002). The average diffusion constant was diffusely elevated in the subcortical white matter. CONCLUSION: Calculating the diffusion constant and anisotropy in the subcortical white matter and corpus callosum in patients with HIV detected abnormalities despite normal-appearing white matter on MR images and nonfocal neurologic examinations. Patients with the highest diffusion constant elevations and largest anisotropy decreases had the most advanced HIV disease. Patients with the lowest viral load levels, who had normal anisotropy and diffusion constants, were receiving highly active antiretroviral therapy.
Adult↗
Sequencing of oligosaccharides by collision-induced dissociation matrix-assisted laser desorption/ionization mass spectrometry.
A study of the collision-induced dissociation post-source decay (PSD) spectra of free oligosaccharides is presented. These spectra, when obtained with helium as collision gas, show (1,5)X fragments containing the reducing end sugar. The presence of these fragments permits Y ions and, consequently, B and C peaks to be identified. This is a common behaviour from which it has been possible to delineate a general method for the easy assignment of the peaks in PSD spectra of underivatized neutral sugars, allowing the sequence of a real unknown to be obtained.
Carbohydrate Sequence↗
Immunohistochemistry of the Hfe protein in patients with hereditary hemochromatosis, iron deficiency anemia, and normal controls.
In 1996 two mutations in Hfe, the gene affected in hereditary hemochromatosis, were identified as C282Y (c.845G. A) and H63D (c.187C. G). Immunohistochemical studies have localized the protein product of Hfe to the deep crypts of the duodenum, the maximum site of iron absorption. To date, there are no published data on the cellular location and regulation of Hfe in patients with hemochromatosis who are homozygous for C282Y. The aim of this study was to identify the cellular localization of Hfe in genotyped individuals and to study possible regulation of this protein by the mutations described in the Hfe gene locus and iron deficiency. Duodenal biopsy specimens and serum for iron, ferritin, and transferrin saturation were taken from controls (n = 10) and patients with hereditary hemochromatosis (n = 10) and iron deficiency anemia (n = 10). All participants were genotyped for C282Y and H63D mutations. Expression of Hfe in the duodenum was demonstrated by immunohistochemistry. Hfe was expressed in the deep crypts of the duodenum in all three groups in a perinuclear fashion. Hfe staining was weaker in the hemochromatosis and iron deficiency patients (mean transferrin saturation 69.6%, SD 23% and 15%, SD 11%, respectively) when compared to controls (mean transferrin saturation 33.1%, SD 15%). There was no difference in the intensity of Hfe staining within the hemochromatosis group who were iron overloaded when compared to their iron-depleted counterparts. In summary, Hfe is expressed strongly in the deep crypts of the small intestine of normal subjects. Homozygosity for C282Y and conditions of iron deficiency result in a downregulation of Hfe. Furthermore, Hfe is not regulated by therapeutic iron depletion in patients with hemochromatosis who are homozygous for the C282Y mutation.
Anemia, Iron-Deficiency↗
Mortality association of enhanced CD44v6 expression is not mediated through occult lymphatic spread in stage II colorectal cancer.
BACKGROUND AND AIMS: In the absence of other metastatic disease, the presence of lymph node metastasis remains the most important determinant of survival in colorectal cancer (CRC). Cluster designation 44 variant 6 (CD44v6) over-expression is associated with worse outcome in all stages of CRC. The CD44v6 is believed to confer metastatic potential through its facilitation of migration, extravasation and proliferation, although the specific means by which it conveys an adverse prognosis in CRC is unknown. The aim of the present study was to determine if CD44v6 over-expression in Stage II CRC subjects was associated with the presence of lymph node micrometastases. METHODS: We assessed tumour CD44v6 expression in 43 randomly sampled subjects who had resections for Stage II CRC between 1984 and 1991 by using immunohistochemistry. Micrometastases were sought in corresponding lymph node (LN) sections using keratin immunohistochemistry. RESULTS: There was a statistical trend between tumour CD44v6 over-expression and mortality (P = 0.09) and a significant relationship between LN cytokeratins and mortality (P = 0.01). There was no association between the detection of LN cytokeratins and tumour CD44v6 over-expression. CONCLUSION: We conclude that the adverse survival effect of CD44v6 over-expression is not mediated though lymphatic spread and postulate that it may therefore facilitate haematogenous metastasis.
Colorectal Neoplasms↗
The detection of cytokeratins in lymph nodes of Duke's B colorectal cancer subjects predicts a poor outcome.
OBJECTIVES: The objectives of this study were to examine the frequency of lymph node micrometastases detected by keratin immunohistochemistry and their relationship with survival behaviour. METHODS: A total of 133 consecutive patients staged as Duke's B, who had curative resection for colorectal cancer (CRC), comprised the study population. Patients who had died of a non-CRC-related cause or who became lost to follow-up were excluded, resulting in an amended population of 100. Study end-points were defined as disease-free survival of 5 years or CRC-related death. Paraffin-embedded lymph node sections were stained with a commercial cytokeratin antibody using a standard avidin-biotin technique. RESULTS: One quarter of subjects had micrometastases. Fifty-six per cent of subjects with positive lymph nodes had an adverse outcome, compared with 11% of subjects with negative nodes. A highly significant association was found between lymph node cytokeratin expression and mortality in both the univariate (log rank P = 0.0001) and multivariate (Cox proportional hazards P = 0.0123) analysis. CONCLUSIONS: Lymph node micrometastases detected by this inexpensive and simple technique are significantly associated with mortality in Duke's B CRC. This technique may be used to select patients for adjuvant chemotherapy.
Biomarkers, Tumor↗
Functional electrical stimulation exercise increases GLUT-1 and GLUT-4 in paralyzed skeletal muscle.
The study purpose was to determine the effect of functional electrical stimulation (FES)-leg cycle ergometer training (30 minutes on 3 d/wk for 8 weeks) on the GLUT-1 and GLUT-4 content of paralyzed skeletal muscle. Biopsy samples of vastus lateralis muscle were obtained pre- and post-training from five individuals with motor-complete spinal cord injury ([SCI] four men and one woman aged 31 to 50 years, 3 to 25 years postinjury involving C5-T8). Western blot analysis indicated that GLUT-1 increased by 52% and GLUT-4 increased by 72% with training (P < .05). This coincided with an increase in the muscle oxidative capacity as indicated by a 56% increase in citrate synthase (CS) activity (P < .05) and an improvement in the insulin sensitivity index as determined from oral glucose tolerance tests (P < .05). It is concluded that FES endurance training is effective to increase glucose transporter protein levels in paralyzed skeletal muscle of individuals with SCI.
Adult↗
Association of the HLA-DRB1*01 allele with spontaneous viral clearance in an Irish cohort infected with hepatitis C virus via contaminated anti-D immunoglobulin.
BACKGROUND/AIMS: The host's immune response may influence the course of hepatitis C virus (HCV) infection. The aim of this study was to examine the distribution of HLA Class II DRB1* alleles in a homogeneous cohort of individuals who were infected with HCV-contaminated anti-D immunoglobulin, and to compare frequencies of alleles in individuals with spontaneous viral clearance to those with chronic HCV infection. METHODS: HLA DRB1* typing was performed on whole blood or serum from 157 females. Of these, 73 had spontaneously recovered from infection (persistently HCV RNA negative), while 84 had chronic HCV infection (persistently HCV RNA positive). A group of 5000 healthy bone marrow donors served as a control population. RESULTS: No significant differences were observed between individuals with spontaneous viral clearance or chronic HCV infection for age, sex, alcohol consumption, source or duration of infection. The DRB1*01 allele was found significantly more frequently in individuals with viral clearance compared to those with chronic infection (27.4% vs. 7.1% p = 0.001, odds ratio OR = 4.9, pc = 0.01). No significant association was shown between severity of liver disease and DRB1* alleles. CONCLUSIONS: DRB1*01 is associated with spontaneous viral clearance in an Irish cohort infected with HCV via contaminated anti-D immunoglobulin. HLA-DRB1* genes do not appear to influence severity of liver disease. These results suggest that host HLA-DRB1* alleles are important contributors to disease outcome.
Adult↗
Polymorphism in intron 4 of HFE does not compromise haemochromatosis mutation results. The European Haemochromatosis Consortium.
Explore the source record for details and available documents.
Alleles↗