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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 19 recordsLinked to original sources
PubMed2006

Immunogenicity of the rF1+rV vaccine for plague with identification of potential immune correlates.

The rF1+rV candidate sub-unit vaccine for plague, formulated by adsorption to alhydrogel, has been demonstrated to be immunogenic in the cynomolgus macaque in a clinically relevant dose-range (5-40 microg of each sub-unit) and regimen. Following two doses of vaccine, a specific IgG titre developed in a dose-related manner with predominance of the IgG1/IgG2 isotypes. Groups of macaques receiving only a single dose of vaccine at the 40 microg dose-level had a significantly reduced peak IgG response and faster decline to baseline. Serum collected at week 5 from 19 immunised animals competed with and displaced murine Mab7.3 from binding to the V antigen in vitro. By week 53 of the schedule, although absolute IgG titres had declined, 17/19 macaque sera tested contained competing antibody, indicating the durability of a functional immune response to rF1+rV in this species. Thirteen of these week 53 sera were passively transferred into groups of naive mice, and all conferred full or partial protection against subsequent challenge of the mice with plague. Generally, those sera which were most competitive with Mab 7.3 for binding to V antigen were fully protective by passive transfer, although one week-53 serum sample was fully protective by passive transfer but not active by competitive ELISA. The early development of protective immunity in macaques was also indicated from the protection conferred on naive mice by the passive transfer of immune macaque serum collected at 2-10 weeks of the immunisation schedule. Serum samples from representative macaques within this time period also inhibited the Yersinia-mediated cytotoxicity of J774 macrophages in a qualitative in vitro assay of type three secretion.

Animals↗
PubMed2006

COX-1 and COX-2 expression in feline oral squamous cell carcinoma.

This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (< or = 1%) of neoplastic cells and its intensity was usually mild to moderate. In contrast, all neoplastic tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.

Animals↗
PubMed2006

Soluble HLA-G expression and renal graft acceptance.

HLA-G is a potentially interesting molecule associated with immunosuppressive function. We survey here the presence of soluble HLA-G (sHLA-G) in serial serum samples of renal transplants. A total of 330 sera of from 65 patients were tested for sHLA-G with ELISA. IgG/IgM antibodies to HLA, and MICA antibodies were also previously tested. After serial analysis of the 65 patients' 330 sera, 50% of 26 patients in functioning group had consistent sHLA-G expression or became positive, in comparison to 20.5% among 39 patients who rejected their transplants (p=0.013). Thus sHLA-G was associated with functioning transplants. Eighty percent (77 of 96) of the HLA IgG positive sera had no sHLA-G expression, while 81.4% (83 of 102) of the HLA-G(+) sera had no HLA IgG (p=0.005), which showed a negative association between sHLA-G and the presence of HLA IgG antibodies (which was previously been shown to be associated with failure). In this preliminary survey, sHLA-G was found in the serum of about 30% of renal transplant patients. sHLA-G had a negative association with allograft failure from chronic rejection, and a negative relationship with the production of HLA IgG antibodies. The significance of sHLA-G in renal transplants remains to be determined.

Adult↗
PubMed2006

MicroRNA enrichment among short 'ultraconserved' sequences in insects.

MicroRNAs are short (approximately 22 nt) regulatory RNA molecules that play key roles in metazoan development and have been implicated in human disease. First discovered in Caenorhabditis elegans, over 2500 microRNAs have been isolated in metazoans and plants; it has been estimated that there may be more than a thousand microRNA genes in the human genome alone. Motivated by the experimental observation of strong conservation of the microRNA let-7 among nearly all metazoans, we developed a novel methodology to characterize the class of such strongly conserved sequences: we identified a non-redundant set of all sequences 20 to 29 bases in length that are shared among three insects: fly, bee and mosquito. Among the few hundred sequences greater than 20 bases in length are close to 40% of the 78 confirmed fly microRNAs, along with other non-coding RNAs and coding sequence.

Animals↗
PubMed2006

Investigation of equine influenza cases exhibiting neurological disease: coincidence or association?

Equine influenza is usually a transient and self-limiting disease. However, during an outbreak of equine influenza in the UK in 2003 there were reports of unusually severe clinical signs among unvaccinated animals. Two influenza-infected horses developed neurological signs, and one was subjected to euthanasia. Post-mortem examination of the brain revealed viral-type non-suppurative encephalitis, and influenza virus antigen was demonstrated by immunolabelling of sections of nasal mucosa. A syndrome known as influenza-associated encephalopathy has been described in man. Although not proved, the data suggest that similar disease mechanisms may operate in horses, and that equine influenza virus infection can result in encephalitis in the natural host, perhaps due to an aberrant host immune response.

Amino Acid Sequence↗
PubMed2006

Aortic and iliac thrombosis associated with angiosarcoma of skeletal muscle in a dog.

A seven-year-old, neutered male greyhound was presented with a history of episodic shifting hindlimb lameness and pain. Ischaemic necrosis of areas of the hindlimb digits and skin and a firm swelling within the medial right thigh musculature were found on physical examination. Investigation demonstrated thrombosis of the terminal aorta and right external iliac artery with ischaemic necrosis of muscular and dermal tissue distal to the sites of thrombosis. The dog was euthanased due to poor prognosis. Necropsy findings were of a poorly differentiated invasive sarcoma of the skeletal muscle of the proximal right hindlimb, thrombosis of the aorta and right external iliac artery and secondary renal glomerulopathy. Immunohistochemistry of the neoplastic tissue indicated angiosarcoma based on expression of CD31 and factor VIII-related antigen. Thrombosis was considered likely to be due to systemic hypercoagulability because of the presence of altered flow characteristics and endothelial damage in the vascular tumour bed. Aortoiliac thrombosis, paraparesis and hindlimb ischaemia are unusual sequelae of angiosarcoma in the dog.

Animals↗
PubMed2006

Major advances in milk marketing: government and industry consolidation.

Federal dairy programs have been instituted to assist dairy farmers in marketing their milk. Milk marketing licenses were issued for city markets in 1933 during the depression. Federal Milk Orders replaced licenses in 1937 with enactment of the Agricultural Marketing Agreement Act. Low prices returned in the late 1940s and Congress passed the Agricultural Act of 1949 creating the support program for milk. Congressional involvement in milk marketing was minimal until passage of the 1977 Farm Bill. A support price adjustment to seek favorable political responses from farmers resulted in higher prices and ultimately higher production. Large expenditures and burdensome supplies caused Congress to make major changes to both programs. Other milk marketing programs have evolved from Congressional actions, including export and promotion programs. The exiting and consolidation of the dairy processors and producers has lead to a reduction in the number of marketing orders.

Agriculture↗
PubMed2005

Use of Medicaid prescription data for syndromic surveillance--New York.

INTRODUCTION: This study explored the utility and value of Medicaid prescription data for statewide syndromic surveillance. METHODS: Daily Medicaid claims forms are transmitted to the New York State Syndromic Surveillance Project as summary counts by ZIP Code, age category, sex, and 18 medication groups. The CUSUM statistic is used to analyze the data daily at the county level with a 7-10-day moving average baseline. The system was evaluated following an outbreak of pertussis in a small institutional setting in a rural county by comparing the county's CUSUM signals for prescriptions for macrolide antibiotics with the onset of the outbreak. RESULTS: A case of pertussis was suspected on July 21, 2004, and was reported to the New York State Department of Health on July 22. Treatment and prophylaxis were initiated on July 22. CUSUM analysis flagged a county-wide increase in macrolide antibiotics on the day of treatment/prophylaxis for the first case and contacts in the outbreak. The following week, approximately 300 contacts received prophylaxis (not all of whom were Medicaid clients), resulting in CUSUM signals during the week (July 28 and 29). CONCLUSION: Medicaid prescription data are routinely collected and readily available for syndromic surveillance. This data source has shown potential value as an indicator of disease activity, as in this case study, in an area where a high concentration of Medicaid recipients reside. However, for the surveillance system to be considered a useful early warning system, additional study is required to determine the best methods for selecting from the automatically generated CUSUM signals those that might be important for public health.

Disease Outbreaks↗
PubMed2005

Parastomal herniation of the gallbladder.

Parastomal hernias can occur in up to 31% of patients following an enterostomy (Cheung in Aust N Z J Surg 65:808-811, 1995). This type of hernia develops through an intentional fascial defect. Commonly, most parastomal hernias involve a reducible segment of omentum, small bowel, or colon. Typically, these hernias are asymptomatic and associated rarely with strangulation or obstruction. Patient preference and clinical scenario may dictate management of these hernias. Non-operative management of parastomal hernias includes abdominal binders and enterostomy belts. Operative management includes a host of options including mesh repair, a new stoma site, or revision. This paper documents the first reported case of a parastomal hernia involving the gallbladder. Optimal technique and site placement of a stoma are also discussed.

Colostomy↗
PubMed2005

Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy.

Macrophages are key components of the inflammatory response to tissue injury, but their activities can exacerbate neuropathology. High-resolution magnetic resonance spectroscopy was used to identify metabolite levels in perchloric acid extracts of cultured cells of the RAW 264.7 murine macrophage line under resting and lipopolysaccharide-activated conditions. Over 25 metabolites were identified including gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter not previously reported to be present in macrophages. The presence of GABA was also demonstrated in extracts of human peripheral blood monocyte-derived macrophages. This finding suggests that there may be communication between damaged central nervous system (CNS) tissue and recruited macrophages and resident microglia, which could help orchestrate the immune response. On activation, lactate, glutamine, glutamate, and taurine levels were elevated significantly, and GABA and alanine were reduced significantly. Strong resonances from glutathione, evident in the macrophage two-dimensional 1H spectrum, suggest that this may have potential as a noninvasive marker of macrophages recruited to the CNS, as it is only present at low levels in normal brain. Alternatively, a specific combination of spectroscopic changes, such as lactate, alanine, glutathione, and polyamines, may prove to be the most accurate means of detecting macrophage recruitment to the CNS.

Amino Acids↗
PubMed2005

Fragmentation of 1 GeV/nucleon iron ions in thick targets relevant for space exploration.

We have measured charged nuclear fragments produced by 1 GeV/nucleon 56Fe ions interacting with aluminium, polyethylene and lead. These materials are relevant for assessment of radiation risk for manned space flight. The data will be presented in a form suitable for comparison with models of nuclear fragmentation and transport, including linear energy transfer (LET) spectrum, fluence for iron and fragments, event-tack- and event-dose-averaged LET, total dose and iron contribution to dose.

Aluminum↗
PubMed2005

Validation of the HZETRN code for laboratory exposures with 1A GeV iron ions in several targets.

A new version of the HZETRN code capable of validation with HZE ions in either the laboratory or the space environment is under development. The computational model consists of the lowest order asymptotic approximation followed by a Neumann series expansion with non-perturbative corrections. The physical description includes energy loss with straggling, nuclear attenuation, nuclear fragmentation with energy dispersion and downshift. Measurements to test the model were performed at the Alternating Gradient Synchrotron and the NASA Space Radiation Laboratory at Brookhaven National Laboratory with iron ions. Surviving beam particles and produced fragments were measured with solid-state detectors. Beam analysis software has been written to relate the computational results to the measured energy loss spectra of the incident ions for rapid validation of modeled target transmission functions.

Aluminum↗
PubMed2005

The urban built environment and overdose mortality in New York City neighborhoods.

Accidental drug overdose continues to be a substantial cause of mortality for drug users. Characteristics of the neighborhood built environment may be important determinants of the likelihood of drug overdose mortality independent of individual-level factors. Using data from the New York City Office of the Chief Medical Examiner, we conducted a multilevel case control study using data on accidental overdose deaths as cases and non-overdose accidental deaths as controls. We used archival data from the New York City Housing and Vacancy Survey and the Mayor's Office of Operations to assess characteristics of neighborhood external (e.g. dilapidation of buildings) and internal (e.g. quality of utilities in houses) built environment. Multilevel analyses were used to assess the relations between the neighborhood built environment and the likelihood of overdose death. Six out of the eight characteristics of the external environment studied and three out of the six characteristics of the internal environment studied were significantly associated with the likelihood of fatal drug overdose in multilevel models after adjusting for individual-level (age, race, sex) and neighborhood-level (income, drug use) variables. Deterioration of the built environment, particularly the external environment, is associated with an increased likelihood of fatal accidental drug overdose. Disinvestment in social resources, psychosocial stressors, neighborhood differences in response to a witnessed overdose, and differences in vulnerability to the adverse consequences of drug use in different neighborhoods may explain the observed associations.

Adolescent↗
PubMed2005

Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative Campath-1H exposure.

A number of recent reports in clinical and experimental intestinal transplantation have suggested that the donor lymphocytes present in and around the gastrointestinal system are potent mediators of graft-versus-host (GvH) reactivity and that GvH responses may contribute to posttransplant morbidity. Therefore, we have tested the proliferative and cytotoxic capabilities of gut-associated lymphocytes from cadaveric donors obtained prerevascularization (pre-r) and about 6 hours postrevascularization (post-r) in recipients pretreated with Campath-1H antibody (alemtuzumab). Mixed lymphocyte reactions (MLR) were performed with lymphoid cells isolated from intestinal epithelial mucosa, lamina propria, and lymph nodes. The pre-r lymphocytes responded strongly to both the recipient and third-party alloantigenic stimulating cells. However, similar preparations from the post-r samples responded in MLR at significantly lower levels (P < .01). This post-r decrease in responsiveness was not observed in similar lymphocyte samples obtained from donors of recipients not treated with Campath-1H. Both the pre-r and post-r samples had similar flow cytometric profiles, suggesting that there was no receptor loss in these lymphoid tissues by the short-term 6-hour exposure to Campath-1H given to the recipient. Conversely, in preliminary experiments where the donor were treated with Campath-1H, it was observed that very few lymphocytes could be obtained from intestinal tissues (n = 3). These results suggested that Campath-1H treatment of the recipient could bring about a drastic reduction in an otherwise strong GvH reactivity by the donor intestinal immune cells.

Alemtuzumab↗
PubMed2005

The impact of Campath 1H induction in adult liver allotransplantation.

BACKGROUND: We report our experience with Campath 1H in adult liver allotransplantation. METHODS: Between December 2001 and February 2004, 77 patients underwent liver transplantation using Campath 1H induction and low-dose maintenance tacrolimus immunosuppression. The control group consisted of 50 patients with similar baseline characteristics and the same eligibility criteria, transplanted under our standard Tacrolimus/steroids regimen. Hepatitis C patients were excluded from the study. RESULTS: Patient and graft survival were similar for both groups. The incidence of rejection was significantly lower in the Campath vs the control group (51% vs 65% at 12 months, P = .009). Tacrolimus trough levels and conversion from Tacrolimus or the addition of other immunosuppressive drugs due to nephrotoxicity were also significantly lower in the Campath 1H group. CONCLUSION: Campath 1H induction with low-dose Tacrolimus maintenance immunosuppression is an effective regimen in reducing acute rejection in adult liver transplantation, while maintaining lower tacrolimus levels and less nephrotoxicity than our conventional immunosuppressive regimen.

Adult↗