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Biomedical subjects

T Fisher

Publications and source records attributed to T Fisher.

At least 37 records · Page 2Linked to original sources

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↗

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↗

The signal-dependent coactivator CBP is a nuclear target for pp90RSK.

We have examined the mechanism by which growth factor-mediated induction of the Ras pathway interferes with signaling via the second messenger cAMP. Activation of cellular Ras with insulin or NGF stimulated recruitment of the S6 kinase pp90RSK to the signal-dependent coactivator CBP. Formation of the pp90RSK-CBP complex occurred with high stoichiometry and persisted for 6-8 hr following growth factor addition. pp90RSK specifically recognized the E1A-binding domain of the coactivator CBP. In addition, like E1A, binding of pp90RSK to CBP was sufficient to repress transcription of cAMP-responsive genes via the cAMP-inducible factor CREB. By contrast with its effects on the cAMP pathway, formation of the pp90RSK-CBP complex was required for induction of Ras-responsive genes. These results provide a demonstration of cross-coupling between two signaling pathways that occurs at the level of a signal-dependent coactivator.

Adenovirus E1A Proteins↗

Induction of specific tolerance through mixed hematopoietic chimerism prevents chronic renal allograft rejection in a rat model.

BACKGROUND: Chronic rejection is the leading cause of late graft loss in kidney transplantation. We tested the ability of mixed hematopoietic chimerism to prevent chronic renal allograft rejection in an established rat model and described possible mechanisms responsible for this tolerance. METHODS: Mixed hematopoietic chimerism was established in lethally irradiated F-344 rats by reconstitution with Lewis bone marrow. Four groups (n = 5 each) received orthotopic kidney transplants: (1) allograft controls, (2) isograft controls, (3) experimental chimeras, and (4) specificity control. After 120 days kidney grafts were examined histologically, immunohistochemically, and for cytokine interferon-gamma, interleukin-2 (IL-2), IL-4, and IL-10 gene transcripts by means of reverse transcriptase polymerase chain reaction techniques. RESULTS: Allograft control group exhibited severe parenchymal fibrosis; isograft control and chimera groups failed to develop this lesion. Immunohistochemical analysis revealed increased CD8+ lymphocytes and ED-1+ monocyte-macrophages infiltrating the tubulointerstitium of control allografts. Interferon-gamma and IL-2 were absent in isografts. IL-4 was absent and IL-10 was positive in all grafts. Chimeras promptly rejected third-party allografts. CONCLUSIONS: Induction of specific tolerance through mixed hematopoietic chimerism prevents chronic renal allograft rejection. These results support the hypothesis of an immunologic basis of chronic rejection and advance previous observations that the induction of specific tolerance enables long-term solid organ transplantation without the use of immunosuppression.

Animals↗

Family mediation.

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Counseling↗

Monoclonal IgM antibodies to GM1 and asialo-GM1 in chronic neuropathies cross-react with Campylobacter jejuni lipopolysaccharides.

We tested monoclonal IgM anti-GM1 and asialo-GM1 antibodies from 6 patients with chronic motor neuropathies for binding to lipopolysaccharides (LPS) from three stains of Campylobacter jejuni. Four of the 6 patients showed strong reactivity with LPS from at least one of the three C. jejuni strains tested as shown by enzyme-linked immunosorbent assay or western blot. Preabsorption with GM1 or asialo-GM1, or blocking with cholera toxin, prevented antibody binding to LPS. These studies indicate that human anti-GM1 or anti-asialo-GM1 antibodies cross-react with LPS from certain strains of C. jejuni, and that bacterial LPS might provide antigenic stimuli for the activation of B cells expressing anti-GM1 antibodies.

Antibodies, Monoclonal↗

The role of general practitioners in the control of breast cancer.

Studies demonstrate that general practitioners have a vital role in the management of women with breast cancer. This includes encouraging women over 35 years to practise breast self examination, those over 40 to have annual breast checks, and those over 50 to have two-yearly mammography.

Adult↗

The peptide FMRFa terminates a discharge in Aplysia bag cell neurons by modulating calcium, potassium, and chloride conductances.

1. Electrical stimulation of an afferent nerve triggers a 30-min period of firing of action potentials in the bag cell neurons of Aplysia californica. This afterdischarge causes the animal to undergo a long-lasting sequence of stereotyped reproductive behaviors culminating in laying of eggs. The connective sheath surrounding the clusters of bag cell neurons is interspersed with a network of particles that are immunoreactive to an antiserum raised against the tetrapeptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa). Because the sheath is known to be rich in processes from the bag cell neurons, these data suggest that an FMRFa-like peptide may be located in neuronal processes that are in close contact with those of the bag cell neurons. 2. Application of FMRFa to bag cell neurons in intact abdominal ganglia effectively suppresses the onset of the afterdischarge in response to electrical stimulation and terminates an ongoing afterdischarge in a reversible manner. 3. Application of FMRFa to isolated bag cell neurons in primary cell culture causes an attenuation of the amplitude of evoked action potentials. This could be attributed in part to an attenuation of the voltage-activated calcium current, which in voltage-clamp experiments was found to be reduced by 10-40%. 4. Application of FMRFa to bag cell neuron in primary culture also causes a hyperpolarization of the membrane potential by activating an outward current with a reversal potential of approximately -67 mV. Ion substitution experiments, together with application of channel blockers, indicate that this current is carried by both potassium and chloride ions. Activation of this current is suppressed by treatment of the cells with either a cyclic AMP analogue or a phorbol ester activator of protein kinase C. 5. FMRFa exerts a powerful inhibitory influence on the bag cell neurons by altering the properties of ion currents involved in both the generation of action potentials and control of the resting potential. This suggests that this neuropeptide plays a role in the regulation of the onset of afterdischarge in vivo.

Animals↗

Urinary excretion of aldosterone metabolite Kelly-M1 in patients with adrenal dysfunction.

Using tetrahydroaldosterone antibody a radioimmunoassay was developed to measure substance Kelly-M1 (K-M1) in human urine. The normal values were lower than observed by Kelly et al. who discovered the catabolite after giving large doses of exogenous aldosterone. While in essential hypertension the excretion of K-M1 was predominantly within the normal range, elevated values were found in most cases of 21-hydroxylase deficiency, both the simple virilizing and salt losing form, primary aldosteronism, renal hypertension and cystinosis. Our findings suggest that K-M1 may be formed from 21-deoxyaldosterone and/or by microbial intervention from aldosterone or its metabolites.

Adrenal Gland Diseases↗

Field independence and simultaneous processing in preschool children.

The present study examined the relations between field independence and simultaneous processing of preschool children as measured by the Preschool Embedded Figures Test (PEFT) and subtests from the Kaufman Assessment Battery for Children (K-ABC), respectively. Data partially supported the assumption that field-independent children would perform significantly better on simultaneous processing tasks in general. Significant age and sex differences on field-independence/field-dependence and simultaneous-processing abilities were found among the embedded figures task and selected portions of the K-ABC. Analysis of embedded figures further indicated age differences, but no significant sex differences.

Achievement↗

The molybdenum-pterin binding protein is encoded by a multigene family in Clostridium pasteurianum.

There are three variants of the molybdenum-pterin binding protein (Mop) encoded by three distinct genes in Clostridium pasteurianum. Nucleotide sequence analysis shows that the three mop genes have greater than 90% homology at the nucleotide level. Upstream from the coding region of each mop gene are potential promoter consensus sequences. Analysis of Mop purified from cells grown under nitrogen-fixing conditions indicates all three genes are expressed. Sequence analysis of the three mop genes and the gene products predicts that there are 10 amino acid replacements among the family. The amino acid replacements are chemically conservative accounting for the co-purification of the three variants of Mop. Protein chemistry data suggest the possibility that glutamic acid residues in Mop may be modified in vivo.

Amino Acid Sequence↗