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Biomedical subjects

E Williams

Publications and source records attributed to E Williams.

At least 55 records · Page 3Linked to original sources

Isolation of bovine viral diarrhea virus from a free-ranging mule deer in Wyoming.

A noncytopathic type 1a bovine viral diarrhea virus (BVDV) was isolated from a free-ranging yearling female mule deer (Odocoileus hemionus) from northwestern Wyoming (USA). The mule deer was emaciated, weak, and salivating, and Arcanobacterium pyogenes was cultured from lung abscesses. Bovine viral diarrhea virus was isolated from lung, however, BVDV antigen was not detected by immunohistochemistry. The BVDV genotype was determined by reverse transcriptase polymerase chain reaction and the RNA sequences from the 5'UTR and E2 genes compared with sequences of a type 1a BVDV isolated from cattle from the same area as the deer. The sequences from the deer BVDV were distinct from those of the bovine type 1a BVDV, but similar to other bovine type 1a BVDVs. Seventy-four (60%) of 124 sera collected from mule deer in this area had serum neutralizing antibody titers to type 1a BVDV of > or = 1:32. The high prevalence of seropositive mule deer and isolation of BVDV suggests that this virus circulates in the mule deer population. The isolate described in this report is the second reported BVDV isolate from free-ranging deer in North America and the first from a mule deer.

Animal Diseases↗

Long-Term outcome of mitral balloon valvotomy in pregnant women.

BACKGROUND AND AIM OF THE STUDY: The study aim was to examine the long-term outcome (nine years) of mitral balloon valvotomy in pregnant patients with severe mitral stenosis. METHODS: Twenty-three patients with severe, symptomatic (NYHA class III/IV) mitral stenosis underwent mitral balloon valvotomy using an Inoue balloon technique during the second trimester of their pregnancy; mean follow up in 19 patients was 5.1 +/- 2.8 years (range: 1 to 9 years). RESULTS: The procedure was successful in all patients. Immediately after valvotomy, the Doppler-derived mitral valve area increased from 0.90 +/- 0.18 to 1.97 +/- 0.36 cm2 (p <0.0001), and the transmitral mean gradient decreased from 15.7 +/- 4.7 to 5.5 +/- 1.6 mmHg (p <0.0001). Four patients had mild worsening of mitral regurgitation, and six developed insignificant interatrial communication immediately after valvotomy. There was no other morbidity or mortality. Patients showed a significant improvement in mean NYHA class, from 3.0 +/- 0.1 to 1.0 +/- 0.02 (p <0.001). Twenty-two patients had normal deliveries; one cesarean section in week 36 resulted in stillbirth. No developmental abnormalities were seen in the babies. At long-term follow up of mothers, the mitral valve area was 1.8 +/- 0.52 cm2; restenosis developed in three patients (16%). One baby died at one week from sudden infant death syndrome, and one at eight months, from pneumonia. All other children showed normal growth, development and speech for their age. CONCLUSION: Mitral balloon valvotomy using the Inoue balloon technique can provide satisfactory immediate relief and long-term outcome in pregnant patients with severe mitral stenosis.

Adolescent↗

Medical students' evaluation of their pathology clerkship experience.

As part of a recent trend among faculties in educational institutions to review and upgrade their courses and teaching methods, the Department of Pathology introduced a questionnaire for assessment of the pathology clerkship experience by the medical students. This was to be completed at the end of their rotation. An evaluation of the results of an entire class indicates that, for the most part, the responses were positive with 82% considering the experience to be of great benefit and 17% of reasonable benefit. The responses were generally more favorable to Anatomical Pathology and Haematology than to Chemical Pathology. The study identified areas where modifications in teaching could be considered, and ways to improve the questionnaire, making it more useful for future assessments.

Clinical Clerkship↗

Male breast cancer. An analysis of four cases and review of the literature.

We report the clinicopathological features and outcome of four cases of carcinoma of the male breast diagnosed at the University Hospital of the West Indies between 1988 and 1998. Male breast cancer is most commonly seen in men over age sixty years, and it exhibits the same prognosis, stage for stage, as the disease in females. However, some researchers report overall poorer survival in men, and explain this on the basis of advanced disease at presentation. Other researchers maintain that the majority of breast cancers in males present at early stages, and exhibit survival similar to that in females. The published literature concerning this uncommon malignancy is reviewed, and the data are compared with the features of our cases.

Aged↗

Ovarian hyperstimulation syndrome associated with clomiphene citrate.

Ovarian hyperstimulation is a recognized complication of ovulation induction with gonadotrophins. The syndrome is becoming more common as the number of women undergoing in-vitro fertilization increases. It is rarely seen in conjunction with clomiphene citrate usage. This case report is of moderate to severe ovarian hyperstimulation in a patient who was treated with clomiphene citrate because of infertility secondary to anovulation. She presented with amenorrhoea for five weeks, lower abdominal pain and a positive urinary human chorionic gonadotrophin (hCG) test. Pelvic ultrasonography was suggestive of a possible ectopic pregnancy with a differential diagnosis of a ruptured ovarian cyst. Diagnostic laparoscopy was done followed by laparotomy. Oophorectomy was performed because the ovary was thought to be complex with solid areas. However, conservative management with avoidance of laparotomy is the recommendation in confirmed cases of ovarian hyperstimulation but this requires a high level of suspicion in patients who have ovulation induction.

Adult↗

Identification and expression of a cDNA for human glycolate oxidase.

The isolation and expression of a human liver cDNA encoding a 43 kDa protein with glycolate oxidase activity is described. The cDNA (HAO1) is 1128 bp and has a 1113 bp open reading frame. Northern blot analysis detects a 1.8 kb mRNA with expression restricted to the liver. The 370 amino acid protein has 89% sequence similarity to glycolate oxidase from mouse liver and 53% similarity to the spinach and Arabidopsis enzymes. The protein has glycolate oxidase activity in vitro, as measured by the reduction of 2, 6-dichlorophenolindophenol in the presence of flavin mononucleotide and glycolate. The genomic sequence is contained within eight exons and encompasses approximately 57 kb of chromosome 20p12. This paper offers the first full functional description of a gene encoding human glycolate oxidase.

2,6-Dichloroindophenol↗

NY-ESO-1 encodes DRB1*0401-restricted epitopes recognized by melanoma-reactive CD4+ T cells.

The NY-ESO-1 gene is expressed by a range of human tumors and encodes HLA-A2-restricted melanoma peptides recognized by CD8+ CTLs. Here we report that the NY-ESO-1 gene also encodes two overlapping, but non-cross-reactive, HLA-DRB1*0401-presented peptides that are recognized by CD4+ T cells. The NY-ESO-1(119-143) peptide was able to induce specific CD4+ T cells in vitro from both an HLA-DRB1*0401+ normal donor and an HLA-DRB1*0401+ patient with melanoma. Bulk and cloned CD4+ T cells produced IFN-gamma specifically in response to, and also lysed, T2.DR4 cells pulsed with peptide NY-ESO-1(119-143) and the autologous tumor cell line, but not a DRB1*0401+ melanoma cell line that does not express NY-ESO-1. Interestingly, the NY-ESO119-143 peptide contains two overlapping putative "core" epitopes recognized by non-cross-reactive anti-NY-ESO-1(119-143) CD4+ T-cell clones. Taken together, these data support the use of this novel DR4-restricted tumor peptide, NY-ESO-1(119-143), or its two "sub-epitopes" in immunotherapeutic trials designed to generate or enhance specific CD4+ T-cell responses against tumors expressing NY-ESO-1 in vivo.

Amino Acid Sequence↗

A novel family of cyclic peptide antagonists suggests that N-cadherin specificity is determined by amino acids that flank the HAV motif.

The classical cadherins (e.g. N-, E-, and P- cadherin) are well established homophilic adhesion molecules; however, the mechanism that governs cadherin specificity remains contentious. The classical cadherins contain an evolutionarily conserved His-Ala-Val (HAV) sequence, and linear peptides harboring this motif are capable of inhibiting a variety of cadherin-dependent processes. We now demonstrate that short cyclic HAV peptides can inhibit N-cadherin function. Interestingly, the nature of the amino acids that flank the HAV motif determine both the activity and specificity of the peptides. For example, when the HAV motif is flanked by a single aspartic acid, which mimics the natural HAVD sequence of N-cadherin, the peptide becomes a much more effective inhibitor of N-cadherin function. In contrast, when the HAV motif is flanked by a single serine, which mimics the natural HAVS sequence of E-cadherin, it loses its ability to inhibit the N-cadherin response. Our results demonstrate that subtle changes in the amino acids that flank the HAV motif can account for cadherin specificity and that small cyclic peptides can inhibit cadherin function. An emerging role for cadherins in a number of pathological processes suggests that the cyclic peptides reported in this study might be developed as therapeutic agents.

3T3 Cells↗

Preparation and Swelling Properties of Poly(NIPAM) "Minigel" Particles Prepared by Inverse Suspension Polymerization.

The characterization of temperature- and pH-sensitive poly-N-isopropylacrylamide (poly-NIPAM) microgel particles, produced by surfactant-free emulsion polymerization, has been extensively reported. In the work described here poly(NIPAM) gel particles, cross-linked with N-N'-methylenebisacrylamide (BA), have been produced using inverse suspension polymerization. These particles have been termed "minigels" here since they are somewhat larger than conventional microgels. Results suggest that minigel particles are formed as a dilute suspension, within the aqueous dispersed (droplet) phase. The hydrodynamic diameter of the minigel particles produced in this work is </=2.5 µm, at 25 degrees C. The effects of temperature and pH changes, variation in cross-linker concentration, and incorporation of a charged comonomer (methacrylic acid, MAA) have been investigated. Both poly(NIPAM-BA) and poly(NIPAM-BA-MAA) minigel particles are temperature sensitive with swelling behavior consistent with comparable microgels. Variations in pH were found to effect the size of minigels containing ionizable groups (such as a carboxylate) by a mechanism of increased electrostatic repulsion of charged groups with increasing pH. Overall, the production of temperature- and/or pH-sensitive polymers by inverse suspension polymerization results in particles with swelling characteristics similar to those produced by emulsion polymerization, albeit with differing particle sizes. Copyright 2000 Academic Press.

Journal Article↗

Enlargement of the receptive field size to low intensity mechanical stimulation in the rat spinal nerve ligation model of neuropathy.

One characteristic of plasticity after peripheral tissue or nerve damage is receptive field reorganization, and enlargement of receptive field size has been suggested to occur in certain models of neuropathic pain. The aim of the present study was to explore whether enlargement of neuronal receptive fields could contribute to the mechanical allodynia found on the ipsilateral paw in the spinal nerve ligation model of neuropathy. After ligation of L(5)-L(6) spinal nerves, all rats developed behavioral signs of mechanical allodynia, while the sham-operated control group displayed no such changes. The characteristics of the evoked responses of the neurones recorded in the dorsal horn of the rats were similar between the spinal nerve ligation, the sham operated control group, and the nonoperated control group, except for spontaneous activity, which was significantly increased in the spinal nerve ligation group. The mean size of the receptive field on the ipsilateral hindpaw, mapped using low-intensity stimulation with 9-g von Frey hair, was significantly increased in the spinal nerve ligation group, as compared to the sham-operated group. No significant difference was seen with 15- or 75-g von Frey hairs. The distribution of the receptive fields over the plantar surface of the paw was similar between the study groups. The enlargement of receptive field for non-noxious touch could be an indication of central sensitization in this model.

Animals↗

Femoral neck and intertrochanteric fractures have different risk factors: a prospective study.

The aim of this study was to determine whether both types of hip fracture, femoral neck and intertrochanteric, have similar risk factors. A prospective cohort study was carried out on community-dwelling elderly women in four areas of the United States: Baltimore, MD; Pittsburgh, PA; Minneapolis, MN and Portland, OR. The participants were 9704 Caucasian women, 65 years and older, of whom 279 had fractured their femoral neck and 222 had fractured their trochanteric region of the proximal femur. The predictors used were the bone mass of the calcaneus and proximal femur, anthropometry, history of fracture (family and personal), medication use, functional status, physical activity and visual function. The main outcome measures were femoral neck and intertrochanteric fractures occurring during an average of 8 years of follow-up. In multivariate proportional hazards models, several risk factors increased the risk of both types of hip fracture; including femoral neck bone density and increased functional difficulty. In hazard regression models that directly compared risk factors for the two types of hip fracture, calcaneal bone mineral density (BMD) predicted femoral neck fractures more strongly than intertrochanteric fractures (OR = 1.16; 95% CI = 1.02-1.31). Steroid use and impaired functional status also predicted femoral neck fractures instead of intertrochanteric fractures. Poor health status (OR = 0.74; 95% CI = 0.55-1.00) predicted intertrochanteric fractures more strongly than femoral neck fractures. We conclude that femoral neck fractures are largely predicted by BMD and poor functional ability while aging and poor health status predispose to intertrochanteric fractures.

Age Factors↗

Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage.

Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) might increase the risk of cerebral ischaemia while stabilizing the clot at the site of aneurysmal rupture, an open-label, dose-escalation safety study has been developed in collaboration with the UK Spontaneous Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid haemorrhage verified by computerized tomography scan or lumbar puncture. Safety evaluation includes clinical observation, monitoring of laboratory variables, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO2) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven 80 microg/kg single bolus (n = 2), NovoSeven 80 microg/kg single bolus followed by continuous infusion at 3.5 microg/kg per h (n = 2) or 7 microg/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcranial Doppler ultrasound and PET studies revealed no evidence of cerebral ischaemia in the first nine patients treated with NovoSeven. The last patient developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation.

Adult↗

Randomized community trial of a breast self-examination skills-building intervention for inner-city African-American women.

OBJECTIVE: Breast cancer is the most common cancer in women, and African-American women are less likely to detect breast cancer at its early stages. Few controlled trials of interventions to increase breast self-examination (BSE) among low-income minority women have been conducted. Our objective was to test a small-group workshop intended to build BSE skills and promote BSE among low-income African-American women. METHODS: A randomized community field trial tested a BSE skills-building workshop based on social cognitive theory of behavior change compared to a matched sexually transmitted diseases prevention workshop, with one- and three-month follow-ups for assessing increased practice of BSE. RESULTS: Women who did not regularly practice BSE and participated in a BSE skills-building workshop were more likely to practice BSE than women in the comparison intervention at the one- (OR = 3.5, p = 0.04) and three-month follow-ups (OR = 4.9, p = 0.01). These results were not related to risk perceptions heightened by the intervention. Across conditions and controlling for covariates in a multivariate model, performing regular BSE was most closely associated with having received any formal BSE instruction. CONCLUSION: BSE skills building can effectively increase use of BSE among low-income African-American women who face multiple and competing health risks. The small-group experience is an important element in fostering norms for practicing BSE and enhancing BSE practices.

Adolescent↗

Risky behaviour in Jamaican adolescent patients attending a sexually transmitted disease clinic.

The prevalence of sexually transmitted diseases (STD) and risky behaviour patterns were studied in 165 adolescents attending a STD clinic in Jamaica. A standardised structured questionnaire, clinical algorithms for STD and serological tests for HIV and syphilitic infection were applied. High prevalences of risky behaviour including young age at onset of sexual activity, especially in boys, (mean age 12.5 +/- 2.5 years); unprotected sexual intercourse (only 4% used condoms consistently); multiple sexual partners (mean 3.8 +/- 2.4 and 1.8 +/- 1.2 for boys and girls, respectively) were found. Marijuana, used by 60% of the boys, was an independent risk factor for dysuria (adjusted Odds Ratio (OR), 2.0; 95% CI, 1.6-3.4). Repeated episodes of STD (33%), coinfection with HIV (1.2%), syphilis (1.2%) and teenage pregnancy (13%) were prominent findings. Educational strategies which promote behaviour intervention at an early age, frequent and consistent use of condoms, abstinence or delayed onset of sexual activity are essential to reducing the HIV/AIDS and STD risk in adolescents in Jamaica.

Adolescent↗

Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration.

P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like selectin counterreceptor that binds to P-selectin, E-selectin, and L-selectin. To determine its physiological role in cell adhesion as a mediator of leukocyte rolling and migration during inflammation, we prepared mice genetically deficient in PSGL-1 by targeted disruption of the PSGL-1 gene. The homozygous PSGL-1-deficient mouse was viable and fertile. The blood neutrophil count was modestly elevated. There was no evidence of spontaneous development of skin ulcerations or infections. Leukocyte infiltration in the chemical peritonitis model was significantly delayed. Leukocyte rolling in vivo, studied by intravital microscopy in postcapillary venules of the cremaster muscle, was markedly decreased 30 min after trauma in the PSGL-1-deficient mouse. In contrast, leukocyte rolling 2 h after tumor necrosis factor alpha stimulation was only modestly reduced, but blocking antibodies to E-selectin infused into the PSGL-1-deficient mouse almost completely eliminated leukocyte rolling. These results indicate that PSGL-1 is required for the early inflammatory responses but not for E-selectin-mediated responses. These kinetics are consistent with a model in which PSGL-1 is the predominant neutrophil P-selectin ligand but is not a required counterreceptor for E-selectin under in vivo physiological conditions.

Animals↗