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Biomedical subjects

D Hodge

Publications and source records attributed to D Hodge.

At least 19 recordsLinked to original sources
PubMed2006

Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome.

CONTEXT: Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by ALMS1 mutations. The natural history of the insulin resistance is unknown, in particular how this relates to changes in body composition. It is also unclear how ALMS1 mutations relate to the characteristic phenotype. OBJECTIVES: Our objectives were to characterize body composition and metabolic parameters, to establish ALMS1 mutation spectrum of United Kingdom AS patients, and to determine whether a genotype-phenotype correlation exists. DESIGN AND PATIENTS: We conducted a cross-sectional cohort study of 12 unrelated subjects with AS. Age-standardized body composition was assessed by anthropometry and dual-energy x-ray absorptiometry and insulin sensitivity by homeostasis model assessment. The exons and intron-exon boundaries of ALMS1 were directly sequenced. SETTING: The study was performed during the annual Alström Syndrome UK multidisciplinary screening clinic. RESULTS: AS patients have early-onset obesity, but body mass index, waist circumference, and body fat from dual-energy x-ray absorptiometry were negatively correlated with age (r = -0.37, P = 0.2; r = -0.84, P = 0.002; and r = -0.6, P = 0.05). Despite this, insulin resistance increased, demonstrated by raised fasting insulin and fall in homeostasis model assessment insulin sensitivity with age (r = -0.64, P = 0.02). ALMS1 mutations were identified in 10 of 12 patients, with a potential founder mutation in exon 16 present in five [np 10775del (C); Del3592fs/ter3597]. No genotype-phenotype correlation was observed. CONCLUSIONS: We identified mutations in ALMS1 in more than 80% of patients with no genotype-phenotype correlation. In AS, severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases. The abdominal obesity, insulin resistance, diabetes, hypertriglyceridemia, and hypertension suggest that AS could represent a monogenic model for the metabolic syndrome.

Absorptiometry, Photon↗
PubMed2005

Cutaneous lymphosarcoma in a stallion.

Multiple cutaneous lymphosarcomas were diagnosed in an 8-year-old Thoroughbred stallion presented for evaluation of lumps on its scrotum. Histological examination of skin biopsy samples showed a homogenous pattern of lymphoid tissue suggestive of a T-cell lymphosarcoma. Immuno-histochemical tests showed a positive reaction to Rabbit/Anti-Human T-Cell, CD3 antibodies confirming T-cell lymphosarcoma. The animal was not treated and was subsequently euthanased.

Animals↗
PubMed2003

Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline.

BACKGROUND: Differential methylation of the two alleles is a hallmark of imprinted genes. Correspondingly, loss of DNA methyltransferase function results in aberrant imprinting and abnormal post-fertilization development. In the mouse, mutations of the oocyte-specific isoform of the DNA methyltransferase Dnmt1 (Dnmt1o) and of the methyltransferase-like Dnmt3L gene result in specific failures of imprint establishment or maintenance, at multiple loci. We have previously shown in humans that an analogous inherited failure to establish imprinting at multiple loci in the female germline underlies a rare phenotype of recurrent hydatidiform mole. RESULTS: We have identified a human homologue of the murine Dnmt1o and assessed its pattern of expression. Human DNMT1o mRNA is detectable in mature oocytes and early fertilized embryos but not in any somatic tissues analysed. The somatic isoform of DNMT1 mRNA, in contrast, is not detectable in human oocytes. In the previously-described family with multi-locus imprinting failure, mutation of DNMT1o and of the other known members of this gene family has been excluded. CONCLUSIONS: Mutation of the known DNMT genes does not underlie familial hydatidiform mole, at least in the family under study. This suggests that trans-acting factors other than the known methyltransferases are required for imprint establishment in humans, a concept that has indirect support from recent biochemical studies of DNMT3L.

Animals↗
PubMed2001

Degradation of albumin in meningococcal sepsis.

We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.

Albumins↗
PubMed2001

CCAAT/enhancer-binding protein beta mediates interferon-gamma-induced p48 (ISGF3-gamma ) gene transcription in human monocytic cells.

Previous studies have identified a novel interferon-stimulated response element-like element, termed gamma-interferon-activating transcription element, within the interferon-stimulating gene factor-3gamma (p48) promoter region that is bound by novel transcription factors in response to stimulation with interferons (IFNs) (Weihua, X., Kolla, V., and Kalvakolanu, D. V. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 103-108). In the present study, we have identified CCAAT/enhancer-binding protein beta (C/EBP-beta) as one of the gamma-interferon-activating transcription element cognate transcription factors by screening a human monophage-derived cDNA library in a yeast one-hybrid system. Electrophoretic mobility shift assay studies suggest that C/EBP-beta dynamically regulates p48 gene expression upon IFN-gamma stimulation by undergoing changes in its heterodimerization partners. Transient transfection studies demonstrate that overexpression of C/EBP-beta strongly enhanced IFN-gamma-induced transcription from the p48 promoter. However, deletion mutants of C/EBP-beta that lack the N-terminal transactivation domain were unable to stimulate the p48 promoter. Western blotting revealed that C/EBP-beta is induced by IFN-gamma stimulation in THP-1-derived macrophages. Collectively, these results suggest that C/EBP-beta plays an important role in the human IFN-gamma signaling pathway by transcriptional regulation of p48 gene expression, an essential component in the IFN signaling pathway.

Base Sequence↗
PubMed2001

Activating Ly-49 NK receptors: central role in cytokine and chemokine production.

In an attempt to understand potential novel functions of receptors in vivo, we evaluated gene expression after cross-linking the activating Ly-49D mouse NK receptor. Gene expression was evaluated using a mouse GEM 2 microarray chip (Incyte Genomics, St. Louis, MO). Each chip displays a total of 8734 elements. The strongly induced genes fell into two categories: 1) soluble factors and 2) apoptotic genes. The majority of the strongly induced mRNAs as analyzed by microarray hybridization were chemokine genes. RNase protection assays and chemokine protein production analysis validated the microarray results, as cross-linking the Ly-49D mouse NK receptor induced high levels of IFN-gamma, lymphotactin, macrophage-inflammatory protein (MIP)1alpha, and MIP1beta. This gene expression was specific because other chemokines were not induced by anti-Ly-49D receptors. In addition, a series of pharmacological inhibitors were used to identify the key signaling pathways involved in the cellular response. The primary Ly-49D signaling for IFN-gamma production is predominantly mediated through Src kinase pathways involving membrane proximal events, whereas MIP1alpha and MIP1beta gene induction is more complex and may involve multiple biochemical pathways. Thus, we conclude that a primary role for the activating NK receptors in vivo may be to trigger soluble factor production and regulation of the immune response. This would place NK cells and their activating Ly-49 receptors as important initiators of microbial immunity and key elements of the innate immune system.

Animals↗
PubMed2001

Normal human keratocyte density and corneal thickness measurement by using confocal microscopy in vivo.

PURPOSE: To quantify keratocyte density according to stromal region and subject age and to measure the thickness of the normal human cornea and its layers in vivo. METHODS: Seventy normal corneas of 70 subjects were examined by confocal microscopy (contact lens wearers were excluded). Ages of subjects ranged from 12 to 80 years, with 10 subjects per decade. Images were recorded by continuously focusing the optical section through the full-thickness central cornea. Two independent human observers manually identified bright objects (keratocyte nuclei) against a dark background to quantify keratocyte density. This method was validated histologically in three human corneas. Thickness measurements were obtained by plotting mean reflected light intensity in images against corneal depth, and calculating distances between intensity peaks that corresponded to corneal layers. RESULTS: Full-thickness central keratocyte density was 20,522 +/- 2,981 cells/mm(3) (mean +/- SD, n = 69). The number of keratocytes in a full-thickness column of central stroma, which had a cross-sectional area of 1 mm(2), was 9624 +/- 1385 cells. Keratocyte density was highest in the anterior 10% of the stroma. Full-thickness keratocyte density was correlated with age (r = -0.62, P < 0.001), decreasing 0.45% per year. Central corneal thickness was 563.0 +/- 31.1 microm (mean +/- SD) and central epithelial thickness was 48.6 +/- 5.1 microm. CONCLUSIONS: This is the first study to quantify regional keratocyte density comprehensively in vivo across a broad age range of normal human subjects. The method was acceptable to both subject and observer, and may prove useful for quantifying keratocyte density in patients with corneal disorders or after corneal surgery.

Adolescent↗
PubMed2000

Cardiovascular and cerebrovascular mortality associated with ocular pseudoexfoliation.

PURPOSE: In recent years, several studies have shown the presence of vascular, cardiac, and other organ pseudoexfoliative material in patients with ocular pseudoexfoliation. The purpose of this study was to determine whether an association exists between ocular pseudoexfoliation and cardiovascular, cerebrovascular, or all-cause mortality. METHODS: This retrospective study included 472 residents of Olmsted County, Minnesota, who were diagnosed with pseudoexfoliation syndrome or pseudoexfoliative glaucoma at Mayo Clinic from 1976 through 1995. Of these 472 cases, 151 subsequently died from 1976 through 1997. Cause of death for these patients, as determined by the National Center for Health Statistics was compared with the entire Rochester, Minnesota, population using Kaplan-Meier analysis. RESULTS: Of the 472 patients with ocular pseudoexfoliation, 358 (76%) were female and 114 (24%) were male. The mean age at diagnosis was 74 years, with a SD of 10 years and a range from 39 to 106 years. Cardiovascular disease resulted in 40 deaths, with a 15-year cumulative probability of cardiovascular mortality of 22%, compared with an expected 20% (no significant difference with P = .19). Cerebrovascular disease resulted in 26 deaths with a 15-year cumulative probability of cerebrovascular mortality of 12%, compared with an expected 10% (no significant difference with P = .38). Finally, the 15-year observed all-cause cumulative mortality was 53% versus an expected rate of 59% (significant difference with P = .0002). CONCLUSIONS: No association was found between ocular pseudoexfoliation and cardiovascular or cerebrovascular mortality. All-cause mortality was significantly less in patients with ocular pseudoexfoliation.

Adult↗
PubMed2000

RSV: Management of the acute episode.

Bronchiolitis is the most common lower respiratory tract infection in infants and is responsible for the majority of paediatric hospital admissions in the winter. Despite significant advances in pharmacotherapy, the management of infants with bronchiolitis has changed little over the years from supplemental oxygen and good fluid management. This paper reviews current treatment options for bronchiolitis, including the use of bronchodilators, adrenaline, steroids and ribavirin. More recent advances, including immunotherapy and intensive care, are discussed.

Acute Disease↗
PubMed2000

Proteus syndrome and immunodeficiency.

A 10 year old boy with Proteus syndrome presented with a pericardial effusion of unknown aetiology. Immunological investigation revealed low serum IgG and IgA, accompanied by low levels of specific antibodies to pneumococcal and haemophilus type B polysaccharides. Circulating lymphocyte surface marker profile revealed T and B cell lymphopenia. This is the first report of hypogammaglobulinaemia occurring in the Proteus syndrome.

Agammaglobulinemia↗
PubMed2000

Effects of laparoscopy on tumor growth.

Laparoscopic resections of colon cancer may affect survival. To address the effects of pneumoperitoneum on tumor cell biology, we developed an experimental model. Mice were injected with colonic tumor cells. Local and systemic effects of pneumoperitoneum were evaluated. Treated mice were randomly assigned to a control group, an open cecectomy group, or a laparoscopic-simulated cecectomy group. When a tumor inoculum was injected into the peritoneal cavity, the frequency of tumors was not significantly different for mice in the laparoscopic-simulated and open cecectomy groups (60% vs 62%, respectively). There was no significant difference in survival time between the laparoscopic-simulated and open cecectomy groups, with median survivals of 24 days versus 22 days, respectively. Finally, when tumor cells were injected subcutaneously, the frequency of tumor nodules and the size and weight of tumors were not different between the two surgical groups. Laparoscopic-simulated cecectomy does not appear to adversely effect local factors or favorably affect systemic factors influencing tumor growth or survival.

Adenocarcinoma↗
PubMed1999

A population-based study of school scoliosis screening.

CONTEXT: Although school-based screening programs for adolescent idiopathic scoliosis are mandated in 26 states in the United States, few program outcomes data exist regarding the effectiveness of such programs. OBJECTIVE: To determine the effectiveness of a community-based school scoliosis screening program. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of children who attended kindergarten or first grade at public or private schools in Rochester, Minn, during 1979-1982. Children were followed up until age 19 years or until they left the school district. MAIN OUTCOME MEASURES: Number of children diagnosed and treated for scoliosis, based on results from scoliosis screenings performed annually in grades 5 through 9, linked to community medical records data; performance characteristics of the screening program. RESULTS: Of the 2242 children screened, 92 (4.1 %) were referred for further evaluation. Of these, 68 (74%) had documented medical or chiropractic evaluation of scoliosis. School screening identified 5 of the 9 children treated for scoliosis but resulted in referrals for another 87 children who were not treated. The cumulative incidence of diagnosed scoliosis in this population was 1.8% (95% confidence interval [CI], 1.2%-2.3%) for curves of more than 10 degrees, 1.0% (95% CI, 0.6%-1.5%) for curves of at least 20 degrees, and 0.4% (95% CI, 0.1 %-0.6%) for curves of 40 degrees or more; 0.4% (0.5% of girls and 0.3% of boys) were treated for scoliosis. The positive predictive value of the school screening program for the identification of treated scoliosis was 0.05 (95% CI, 0.048-0.052), with 448 children needed to screen to identify 1 child who subsequently received treatment. The percent positive agreement across consecutive years of screening varied from 7% to 30%. CONCLUSION: In this population, school scoliosis screening identified some children who went on to receive treatment but referred many more who did not. These data should be considered in making decisions regarding school scoliosis screening.

Adolescent↗