Biomedical subjects
Publications and source records attributed to D Fisher.
A 5-year-old girl with chronic granulomatous disease (CGD) and esophageal narrowing is described. To date, only two cases of esophageal involvement in CGD have been reported. We present a third, well-documented case and a brief review of the literature.
Five cyclin-like genes, cig1, cig2/cyc17, mcs2, puc1 and cdc13, have been discovered in S. pombe to date. It is not yet clear what their functions are or even whether they are all involved with control of the cell cycle. Conflicting data for cig1 and cig2/cyc17 have obscured analysis of their function and cig1 remains largely uncharacterized, although clues to the role of cig2/cyc17 have emerged. There is genetic data available for the more distant cyclin homologue mcs2, which has an essential although as yet unspecified role. Puc1 may be involved in regulation of exit from the cell cycle. The first cyclin to be discovered, and the best understood, is cdc13 which with cdc2 promotes mitosis. Studies of the roles of cdc2 and cdc13 in the overall ordering of the cell cycle suggest that cdc13 and probably other cyclins are key regulators, maintaining the order of S phase and mitosis during the cell cycle.
BACKGROUND: Until recently Penicillium marneffei rarely caused human disease. It is now a frequently encountered opportunistic mycosis in HIV positive residents of, and travellers to, south-east Asia. AIMS: To review aspects of clinical presentation, pathology, treatment, epidemiology and ecology of P. marneffei. To report a case of disseminated P. marneffei occurring in the Northern Territory which illustrates many typical clinical and pathological features of this infection. CASE PRESENTATION: A Burmese immigrant presented to Royal Darwin Hospital, Australia with a non-specific, subacute, febrile illness and a diffuse papular rash. The etiological agent was Penicillium marneffei, disseminated in association with advanced HIV infection. The typical travel history and umbilicated papular rash were recognized on admission. Fungal stains of skin biopsies and touch smears facilitated rapid diagnosis, and early antifungal therapy resulted in clinical cure. CONCLUSIONS: Early distinction of penicilliosis from other opportunistic mycoses, tuberculosis, Leishmaniasis, and molluscum contagiosum is critical for effective management. The characteristic histological and mycological properties of P. marneffei are easily recognizable if the diagnosis is considered. In view of geographic proximity, travel and immigration from endemic areas, Australia should expect further imported penicilliosis as illustrated by this case report.
To determine the effect of liver disease on the pharmacokinetics of rocuronium, the authors administered 0.6 mg/kg (twice the ED95) to 10 patients with liver disease and compared these results to values in 10 healthy surgical patients. Anesthesia was induced with thiopental and maintained with isoflurane (0.9%-1.1% end-tidal concentration) and nitrous oxide (60%). Venous blood samples were obtained for 6 h after rocuronium injection and plasma concentrations were measured using gas chromatography. Pharmacokinetic differences between groups were determined using a population-based pharmacokinetic analysis (NONMEM). Hepatic impairment did not alter the plasma clearance of rocuronium (217 +/- 21.8 mL/min, mean +/- SE, for both groups), but did increase the volume of the central compartment (5.96 +/- 1.01 L for controls, 7.87 +/- 1.33 L for patients with liver disease) and volume of distribution at steady state (16.4 L for controls, 23.4 L for patients with liver disease). In turn, elimination half-life was longer in patients with liver disease (111 min) compared to controls (75.4 min). The authors conclude that liver disease alters the pharmacokinetics of rocuronium by increasing its volume of distribution. The longer elimination half-life might result in a longer duration of action of rocuronium in patients with liver disease, particularly after prolonged administration.
Intrathoracic amyloidosis affecting the lungs or mediastinum is rare, and mediastinal lymphadenopathy in the absence of pulmonary involvement is even more rare. The case history is presented of a previously healthy man who developed nodular mediastinal amyloidosis without pulmonary involvement. Diagnosis was made by percutaneous fine needle biopsy.
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We show here that the state of the p34cdc2-p56cdc13 mitotic B cyclin complex determines whether a fission yeast cell undergoes S phase or mitosis. Mutants defective for p56cdc13 reset to G1 and rereplicate their DNA, while cells completely lacking the p34cdc2-p56cdc13 complex undergo multiple rounds of S phase. In contrast, formation of the p34cdc2-p56cdc13 complex in G1 promotes cells inappropriately into mitosis. We propose that the temporal order of S phase and mitosis is maintained by the presence or absence of the p34cdc2-p56cdc13 complex.
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The composition of the erythrocyte plasma membrane is extensively modified during the intracellular growth of the malaria parasite Plasmodium falciparum. It has been previously shown that an 80-kD phosphoprotein is associated with the plasma membrane of human red blood cells (RBCs) infected with trophozoite/schizont stage malaria parasites. However, the identity of this 80-kD phosphoprotein is controversial. One line of evidence suggests that this protein is a phosphorylated form of RBC protein 4.1 and that it forms a tight complex with the mature parasite-infected erythrocyte surface antigen. In contrast, evidence from another group indicates that the 80-kD protein is derived from the intracellular malaria parasite. To resolve whether the 80-kD protein is indeed RBC protein 4.1, we made use of RBCs obtained from a patient with homozygous 4.1(-) negative hereditary elliptocytosis. RBCs from this patient are completely devoid of protein 4.1. We report here that this lack of protein 4.1 is correlated with the absence of phosphorylation of the 80-kD protein in parasite-infected RBCs, a finding that provides conclusive evidence that the 80-kD phosphoprotein is indeed protein 4.1. In addition, we also identify and partially characterize a casein kinase that phosphorylates protein 4.1 in P falciparum-infected human RBCs. Based on these results, we suggest that the maturation of malaria parasites in human RBCs is accompanied by the phosphorylation of protein 4.1. This phosphorylation of RBC protein 4.1 may provide a mechanism by which the intracellular malaria parasite alters the mechanical properties of the host plasma membrane and modulates parasite growth and survival in vivo.
We have examined the performance and reproducibility of an automated DNA profiling system which is based on the multiplex amplification of 4 tetrameric STR loci-HUMVWFA31/A. HUMTH01, HUMF13A1 and HUMFES/FPS. The system was able to type 100 pg of purified, undegraded, genomic DNA. At lower concentrations of DNA (below 100 pg), allelec drop-out occurred due to stochastic differences in allele copy number. Minor variation of individual PCR reagent concentrations or cycling temperatures did not result in a significant effect on the efficiency of amplification of any of the 4 loci in the quadruplex system. More substantial variation of reagent concentrations or cycling temperatures outside the optimum range of the system resulted in a reduction or complete loss of signal for one or more loci. This was also observed at high ionic strength or extreme pH. However, under all reagent concentrations and conditions studied, no artefact bands that could potentially result in the mistyping of a sample were apparent within the read region (130-240 bases) of the gel. Evaluation of both native and denaturing polyacrylamide gels revealed that, although native gels displayed faster run times, the sizing precision of such gels for certain STR loci was lower than that of denaturing gels. Also, artefact bands may be present within the read region of native gels. In conclusion the quadruplex amplification system described, coupled with automated fluorescence-based detection on denaturing polyacrylamide gels, appeared to be a robust and reliable system for individual identification.
Alkaline phosphatase (ALP) isoforms can be distinguished from each other by their partition characteristics in aqueous two-phase systems composed of water-soluble polymers, the phases of which are differentially sensitive to the presence of glycan-phosphatidylinositol anchors. Compared with detergent-based systems, the aqueous polymer systems have the advantage that micelle formation does not take place. Partition of anchor-intact and anchor-degraded molecules in the latter systems is further improved by attachment of a hydrophobic ligand to one of the phase forming polymers. In this way, anchor-intact molecules can be separated from molecules with degraded anchors in a single partition step. The method has been used to confirm that ALP in human serum is predominantly anchor degraded, whereas in bile it retains its anchor intact.
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Covalent attachment of poly(ethylene glycol) (PEG) to proteins produces conjugates with altered/improved physicochemical and biological properties which depend upon the number of PEG chains linked. Quantification of the attached PEG is however not a trivial issue. The partition coefficient, K, of the PEG-protein conjugate in PEG/dextran two-phase systems provides a quantitative measure for the degree of modification. A linear relationship between log K and the number of PEG chains was observed in fractionated PEG-modified-granulocyte-macrophage colony stimulating factor conjugates having 1 to 3 substitutions. Furthermore, in mixtures of PEG-bovine-serum-albumin conjugates with increasing degrees of modification, a linear relationship was found between log K and n, the average substitution. The increment in log K per PEG chain added is protein specific and this suggests that the interactions between the PEG-protein conjugate and the polymers in the phase system are more complex than just a simple affinity of the PEG for the PEG-rich top phase. Increasing the polymer concentration in the phase system produces larger increments in log K per PEG molecule attached and the proportionality between log K and number of PEG molecules is only compromised for conjugates with high degree of substitution when partitioned in biphasic systems of high concentration of polymers.
When injected intravenously, lipid vesicles labeled with 99mTc by means of a lipophilic chelator dipalmitoylphosphatidylethanolamine-diethylenetriaminetetraacetic acid (PE-DTTA) are rapidly accumulated by the mononuclear phagocytic system (MPS). By derivatizing the membrane surface with the lipid-polymer complex dipalmitoylphosphatidylethanolamine-monomethoxy polyethylene glycol 5000 (PE-MPEG), MPS uptake can be suppressed and loss of 99mTc label from the lipid surface reduced depending upon both PE-DTTA and PE-MPEG content. For vesicles containing 20% PE-DTTA, addition of PE-MPEG makes no difference to their rate of clearance from the circulation. However for vesicles containing 2% PE-DTTA, addition of more than 0.8% PE-MPEG increases circulation half-life, suppresses liver uptake and reduces renal clearance of the 99mTc label. The molar ratio of reducing agent (Sn) to chelator (PE-DTTA) is critical to efficient and reproducible labeling. For vesicles containing 2% PE-DTTA at a lipid concentration of 100 mM, a Sn/DTTA ratio of 0.35 gives close to optimal labeling. Variation in the Sn/DTTA ratio by a factor of two negatively impacts upon both labeling efficiency in vitro and circulation half-life in vivo. Potential uses for technetium-labeled lipid vesicles with extended circulation half-life are discussed.
Cystic lymphangioma is a very rare condition of unknown aetiology. It is generally regarded as a developmental malformation in which obstruction or agenesis of lymphatic tissue results in lymphangiectasia secondary to lack of normal communication of the lymphatic system. Most lymphangiomas occur in the neck (75%) and axillary region (20%). Lymphangiomas may rarely occur in the retroperitoneum, mediastinum, mesentery, omentum, colon, pelvis, groin, spleen, bone and skin. We present a case of multicompartmental tuberculous lymphangioma extending continuously from the superior posterior mediastinum through the retroperitoneum to the right groin, which responded to needle aspiration and antituberculosis drug therapy.
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