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Biomedical subjects

T Fisher

Publications and source records attributed to T Fisher.

At least 19 recordsLinked to original sources
PubMed2001

Effect of short-term exposure to chlorpyrifos on developmental parameters and biochemical biomarkers in Chironomus riparius Meigen.

Chironomus riparius Meigen were exposed to sediment spiked with 0, 0.01, 0.05, and 0.10 mg chlorpyrifos/kg dry sediment for 48 h as late third-instar larvae. Acetylcholinesterase activity, glutathione-S-transferase activity, burrowing behavior, emergence time, and adult dry weight were measured to determine which were the most sensitive biomarkers of exposure and effect for short-term sublethal exposures. There was a significant drop in acetylcholinesterase activity at the two highest concentrations, but no effect on glutathione-S-transferase activity. Behavioral and life history biomarkers were sensitive only to the highest concentration of chlorpyrifos. The association of life history changes (female weight and male emergence times) with a significant inhibition of acetylcholinesterase activity suggests that this can be used as a biomarker of exposure and effect.

Acetylcholinesterase↗
PubMed2001

Hodgkin's disease with an intrasinusoidal pattern of infiltration. A report of two cases.

The histological distinction between Hodgkin's disease (HD) and anaplastic large cell lymphoma (ALCL) may be difficult but is important as the two conditions have different clinical behaviours, prognoses and responses to therapy. Morphological appearances that have been emphasised as favouring the diagnosis of ALCL rather than HD include the identification of neoplastic cells permeating sinusoidal spaces. We document two cases of Hodgkin's disease with classical morphological and immunohistochemical features of nodular-sclerosis subtype (HDNS) but with striking sinusoidal involvement by neoplastic cells. In each case, the CD30 positive/CD15 positive immunophenotype of the neoplastic cells was characteristic of HD without expression of any of the other antigens normally associated with ALCL. HD is generally considered to be a morphological diagnosis and, in those laboratories in which it is not possible to use wide panels of antibodies for the confirmation of the diagnosis, the identification of sinusoidal infiltration by the neoplastic cells in HD may lead to the mistaken impression of ALCL.

Adult↗
PubMed2001

Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality.

The discovery of toxin-antitoxin gene pairs (also called addiction modules) on extrachromosomal elements of Escherichia coli, and particularly the discovery of homologous modules on the bacterial chromosome, suggest that a potential for programmed cell death may be inherent in bacterial cultures. We have reported on the E. coli mazEF system, a regulatable addiction module located on the bacterial chromosome. MazF is a stable toxin and MazE is a labile antitoxin. Here we show that cell death mediated by the E. coli mazEF module can be triggered by several antibiotics (rifampicin, chloramphenicol, and spectinomycin) that are general inhibitors of transcription and/or translation. These antibiotics inhibit the continuous expression of the labile antitoxin MazE, and as a result, the stable toxin MazF causes cell death. Our results have implications for the possible mode(s) of action of this group of antibiotics.

Anti-Bacterial Agents↗
PubMed2001

Preliminary analyses of Hebrew verbal fluency measures.

Hebrew language versions of phonemic and semantic fluency were administered to samples of normal control participants and individuals who had been hospitalized for 24 hr following a head injury. For the control sample, verbal fluency tasks were normally distributed and significantly correlated with education. The head injury sample's word generation was significantly lesser than that of the control's and not at all related to educational attainment. The findings provide evidence for the use of Hebrew fluency measures for clinical assessment and the need for collection of normative data across education levels.

Adult↗
PubMed2001

Variability in acetylcholinesterase and glutathione S-transferase activities in Chironomus riparius Meigen deployed in situ at uncontaminated field sites.

An in situ system was used to expose fourth instar Chironomus riparius Meigen larvae for 48-h at 13 uncontaminated river sites across southeast England. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities were measured in individual larvae recovered from these sites. Activities of both biomarkers varied almost twofold across the sites, with statistically significant differences detectable between sites. There were no clear relationships between biomarker activities and physical or chemical characteristics measured at each site. This study shows that biomarker measurements can be used successfully in conjunction with an in situ system. However, the results of statistically significant biomarker results must be treated with caution because natural variability in responses can occur even in the absence of toxicant exposure.

Acetylcholinesterase↗
PubMed2000

Advance directives: older adults with dementia.

The benefits and risks for older adults with dementia executing advance directives are discussed. Salient issues related to decision-specific capacity and models for advance planning and end-of-life decisions by cognitively impaired older adults are presented.

Advance Directives↗
PubMed2000

The effectiveness of NGO campaigning: lessons from practice.

This article looks at the lessons learned in reviewing two long-running international campaigns, one to promote breast-feeding in Ghana, and the other against the use of child labor in the carpet industry in India. In particular, it focuses on understanding the nature of campaigns and what makes them effective. It asserts that campaigns are not linear or mechanistic, but need to be understood as passing through various stages and requiring different kinds of action at different levels and at different times. The variety of work and skills thus required makes it vital that the various organizations involved collaborate with each other. In particular, grassroots mobilization has a role that is often forgotten in bringing about sustained policy change.

Africa↗
PubMed2000

Molecular and antigenic characterization of a highly evolved derivative of the type 2 oral poliovaccine strain isolated from sewage in Israel.

An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40 degrees C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A(481) to G in the 5' untranslated region and the VP1 amino acid I(143) to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for approximately 6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication.

5' Untranslated Regions↗
PubMed2000

Creating interpretation guidelines for the Hebrew trail making test.

The Hebrew language version of the Trail Making Test (TMT; Army Individual Test Battery, 1944) was administered to a group of normal control participants as well as a sample of outpatients approximately 1 year following a head injury. A ratio of TMT-B to TMT-A performance was computed in an effort to establish usable cutting scores for the Hebrew TMT. A ratio of 2.26 was observed to result in 63% sensitivity and 77% specificity for the sample, with positive predictive power of 71% and negative predictive power of 70%. A more stringent cutoff of 3.09 reduced sensitivity (22%) and negative predictive power (44%). In contrast, specificity (97%) and positive predictive power (86%) were greatly improved once the speed of TMT-A performance was also considered. The more conservative cutoff is considered appropriate when a finding is indicative of pathological performance.

Adult↗
PubMed1999

Total colectomy versus limited colonic resection for acute lower gastrointestinal bleeding.

BACKGROUND: Acute lower gastrointestinal bleeding (ALGB) of the colon can be problematic to diagnose. The purpose of this study was to review our experience with ALGBs and to determine any differences between limited colon resection (LCR) and total/subtotal colon resection (TCR). METHODS: A retrospective study located 77 patients with ALGB, who required 2 or more units of packed red blood cells prior to surgery, and who were taken to the operating room from 1987 to 1997. RESULTS: Fifty LCRs and 27 TCRs were performed during this 10-year period. Recurrent bleeding was significantly more common in the LCR group than in the TCR group (18% versus 4%). Morbidity and mortality were not significantly different. CONCLUSIONS: Owing to the misconception of a higher morbidity with TCR, it has been considered a "last resort" instead of a more expeditious therapy with similar morbidities and mortalities. TCR should be considered more often in the management of these patients.

Acute Disease↗
PubMed1999

Tolerance induction permits the development of graft-versus-host disease: donor-mediated attack following small bowel transplantation in mixed chimeras.

The induction of tolerance to organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. We have shown that tolerance induced through the creation of mixed allogeneic bone marrow chimeras allows for the long-term engraftment of cardiac and small bowel allografts across strong multiple major histocompatibility barriers. The possibility that tolerance might render the host susceptible to graft-versus-host disease (GVHD) has not been investigated in this or other models of tolerance. To test this possibility chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post bone marrow transplant (BMTx) by flow cytometry of lymphocytes from reconstituted animals. ACI/Lew chimeras (ALC), Lewis/ACI F1 (LACF1), and Lewis (LEW) rats all received heterotopic ACI vascularized small bowel grafts. A second group of chimeras received small bowel grafts from ACI rats pretreated with low dose irradiation to eliminate T-cells from the graft. LEW-->LEW small bowel isografts were also performed. Animals were examined for evidence of GVHD by clinical signs and histologic examination of biopsied tissues. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 rats developed severe lethal GVHD following ACI small bowel transplant. Bone marrow chimeras, ALC (n = 6), developed fatal GVHD in a similar fashion after receiving a small bowel transplant. LEW-->LEW isografts and chimeras receiving bowel from irradiated ACI rats survived long term without GVHD while ACI-->LEW allogeneic transplants all underwent acute rejection. GVHD or its absence was confirmed histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras (1.87) and LACF1 (5.4) receiving allografts, but not in isografts or chimeras receiving irradiated allogeneic transplants. Analysis of cytokines in the tongues of rats undergoing GVHD showed elaboration of Th1 type proinflammatory cytokines which was not seen in isografted rats or rats receiving preirradiated small bowel. These results demonstrate that tolerance induction through mixed chimerism results in susceptibility to small bowel induced GVHD. Preirradiating the donor bowel prior to SBTx can prevent GVHD.

Animals↗
PubMed1999

A new variant of echovirus 4 associated with a large outbreak of aseptic meningitis.

BACKGROUND: A large outbreak of aseptic meningitis which began in April 1997 involved hundreds of cases in all geographical regions of Israel and the Palestinian Authority, peaked between June and September, and lasted until December. OBJECTIVES: We have investigated the virus associated with the outbreak to determine its serotype and molecular type and to establish epidemiological links. DESIGN: Virus strains isolated from 210 clinical samples were serotyped by neutralization using LBM and WHO antiserum pools and two echovirus 4 (EV4)-specific antisera, and by immunofluorescence using a monoclonal antibody. RNA was extracted and a 435 base long fragment derived from the 5'UTR of the genome was amplified by RT-PCR using common primers, and sequenced. Sequences were compared to echoviruses 4, 6 and 7 prototypes from ATCC, and to other echoviruses sequences from the EMBL/Genbank data base. RESULTS: The outbreak isolates were identified by the EV4 type-specific antisera and the monoclonal antibody but not with the WHO pools. Very few isolates could be typed by the LBM pools. The EV4 isolates accounted for 68% of all enterovirus isolates in our laboratory in 1997. The age distribution of the patients was: 0-11 month, 11.2%; 1-4 years, 16.1%; 5-9 years, 31.8%; 10-14 years, 9.9%; 15-20 years, 9.5%; 21-44 years, 21.5%; and > 45 years, 0%. Males between 1 and 14 years of age were affected more frequently than females of the same age. The sequences of 25 of 28 EV4 isolates analyzed were closely related to each other (> 95% homology) and the remaining three isolates had < 95% homology to the others and to each other. Interestingly, the outbreak strains were less closely related to the EV4 prototype, than to several other echoviruses. Three closely related subgroups were identified which correlated with geographical distribution but the temporal distribution did not reveal links leading to the source of the outbreak. CONCLUSION: The outbreak was caused by a variant of EV4 which apparently did not circulate in the area before and thus was capable of causing a widespread infection.

Disease Outbreaks↗
PubMed1999

Genetic variation of three tetrameric tandem repeats in four distinct Israeli ethnic groups.

The allele frequency distributions of three STR loci amplified by PCR have been studied in four Israeli communities: Ashkenazi Jews and three non-Ashkenazi groups, namely Moroccan, Yemenite, and Ethiopian Jews. The loci analyzed were CSF1PO, TPOX, and HUMTHO1. The typing was performed in sequencing polyacrylamide gels under denaturing conditions that could separate alleles with differences of a single base. The population data were analyzed with respect to Hardy-Weinberg (H-W) equilibrium and found that all loci meet the H-W expectations. No-ticeable differences were encountered between the four Jewish ethnic groups studied hereby indicating the importance of establishing a local database to be used in human identity testing in these different Israeli Jewish groups.

DNA↗
PubMed1998

Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.

BACKGROUND: These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection. METHODS: Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft. RESULTS: Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%. CONCLUSION: IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.

Animals↗
PubMed1997

Graft versus host disease in rats made tolerant for organ allografts.

Tolerance for organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. A potential hazard of tolerance is the susceptibility to graft vs host disease (GVHD) due to unresponsiveness to alloantigen. This study sought to determine if our model of tolerance induction results in susceptibility to GVHD. Chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post-BMTx by flow cytometric analysis of recipient spleens for the presence of ACI cells. ACI/Lew chimeras (ALC), animals that reconstituted only with syngeneic (Lewis) marrow (so-called failed chimeras), and ACI/Lew F1 (LACF1) hybrid rats were all given 200 x 10(6) ACI splenocytes i.v. Animals were examined for evidence of GVHD. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 (n = 6) rats developed severe lethal GVHD following ACI splenocyte injection. Similarly, ALC (n = 6) developed fatal GVHD. Animals that reconstituted only with syngeneic Lewis marrow (failed chimeras) showed no signs of illness. GVHD was confirmed histologically and immunohistochemically. Failed chimeras receiving ACI splenocyte challenge showed no evidence of GVHD histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras and hybrids but not in the failed chimeras. We conclude that tolerance induction by mixed chimerism results in susceptibility to GVHD if enough donor lymphoid tissue is given to the host at the time of organ transplant. Animals that are not mixed chimeras (failed bone marrow transplant) rejected the allogeneic splenocytes as evidenced by their lack of disease. Tolerance may therefore make the host defenseless against fatal GVHD.

Animals↗
PubMed1997

Surgical morbidity, mortality, and long-term survival in patients with peripancreatic cancer following pancreaticoduodenectomy.

BACKGROUND: Surgical resection of the primary tumor in peripancreatic cancer has been associated with an improved survival and decreased morbidity in the recent literature. The purpose of this review was to analyze the results at a single institution. METHODS: Between 1985 and 1995, 88 patients underwent a pancreaticoduodenectomy for adenocarcinoma of the pancreatic head region and had complete long-term follow-up. Patient records were reviewed to determine morbidity, mortality, and survival. RESULTS: Tumor histology included pancreatic head adenocarcinoma (n = 46), ampullary adenocarcinoma (n = 28), duodenal adenocarcinoma (n = 8), and cholangiocarcinoma (n = 6). Morbidity occurred in 26 patients (29%). Perioperative mortality was seen in 6 patients (7%). No perioperative mortality was seen over the last 3 years, which included 33 patients. The mean follow-up was 29 months, with a median survival of 19 months. At last follow-up, 24 patients were alive without disease with an average survival of 43 months (1 to 141). There were 54 patients who died with cancer with an average survival of 21 months (1 to 117). Based on Kaplan and Meier statistical analysis the estimated survival was 47% at 2 years and 25% at 5 years. The location of the primary tumor (P = 0.0006) and the presence of positive lymph nodes (P = 0.05) was shown to have a negative impact on survival. CONCLUSION: Pancreaticoduodenectomy can be done with acceptable morbidity and mortality. The outlook with this disease remains poor, but long-term survival can be achieved in some patients.

Adenocarcinoma↗
PubMed1997

Induction of anti-GM1 ganglioside antibodies by Campylobacter jejuni lipopolysaccharides.

A frequent association exists between acute motor neuropathy, antecedent Campylobacter jejuni (CJ) and anti-GM ganglioside antibodies. Despite the chemical and immunological similarity between CJ lipopolysaccharides (LPS) and GM1, the mechanism of induction of anti-GM1 antibodies is still unclear. We used CJ LPS to immunize rats, mice and immunodeficient mice lacking in NK, CD8+ or T-cell populations. None of these animals developed significant anti-GM1 titers. However, rats immunized with keyhole limpet hemocyanin which contains the cross-reactive sugar epitope Gal(beta1-3)GalNAc developed high titers of IgM anti-GM1 antibodies. This occurred only after these rats were given an intraperitoneal injection of CJ LPS. These results suggest that a glycoprotein antigenic stimulus can induce B-cells which are autoreactive to ganglioside but which remain anergic. A second stimulus with a cross-reactive LPS can then overcome the anergy to induce autoantibody production. A similar mechanism may explain the occurrence of GM1 antibodies in patients after CJ enteritis.

Adjuvants, Immunologic↗