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Biomedical subjects

D Sheehan

Publications and source records attributed to D Sheehan.

At least 37 records · Page 2Linked to original sources

Costs of postpartum care: examining associations from the Ontario mother and infant survey.

A cross-sectional survey of 1,250 mothers of "normal" newborn infants was conducted to assess mother and infant characteristics as well as the costs of health and social services used in the first 4 weeks after discharge from hospital in the province of Ontario, Canada. Each mother was asked to recall use of services for herself and her infant. This utilization was multiplied by the unit cost of each service and summed to arrive at the total cost of services used. Although re-admission rates were low (1% for mothers, 4% for infants), costs associated with hospital and emergency room care ($194 on average per mother/infant dyad) accounted for the greatest proportion of total health-care costs. Physician or midwife visits, which were received by almost all mothers, were the next most costly service ($128 on average per dyad). Mothers with incomes under $20,000 had more medical costs than those with higher incomes. Costs of community nursing care ($86 on average per dyad) were higher for mothers with more than 5 self-identified learning needs (e.g., infant feeding, infant care and behaviour, emotional changes in self, signs of illness in infant); perception of their own health as poor; perception of inadequate help and support at home; many signs and symptoms of depression; and postpartum hospital stay of 48 hours or less. Costs for social work visits were higher for mothers with depression and mothers with low incomes. Total health and social service costs were double for mothers with family incomes under $20,000 ($788 vs. $399 on average per dyad) and for mothers with clinical depression ($845 vs. $413). Specifically, nursing care costs were greater for mothers with high depression scores ($135 vs. $81).

Adult↗

Heat shock proteins--modulators of apoptosis in tumour cells.

Apoptosis is a genetically programmed, physiological method of cell destruction. A variety of genes are now recognised as positive or negative regulators of this process. Expression of inducible heat shock proteins (hsp) is known to correlate with increased resistance to apoptosis induced by a range of diverse cytotoxic agents and has been implicated in chemotherapeutic resistance of tumours and carcinogenesis. Intensive research on apoptosis over the past number of years has provided significant insights into the mechanisms and molecular events that occur during this process. The modulatory effects of hsps on apoptosis are well documented, however, the mechanisms of hsp-mediated protection against apoptosis remain to be fully defined, although several hypotheses have been proposed. Elucidation of these mechanisms should reveal novel targets for manipulating the sensitivity of leukaemic cells to therapy. This review aims to explain the currently understood process of apoptosis and the effects of hsps on this process. Several proposed mechanisms for hsp protection against apoptosis and the therapeutic implications of hsps in leukaemia are also discussed.

Animals↗

Chemical modulation of chemotherapy resistance in cultured oesophageal carcinoma cells.

Oesophageal carcinoma is a common form of cancer in developing countries, especially in the Caspian littoral and northern China. In contrast, it has a much lower incidence in Japan, the U.S.A. and western Europe. Certainly in the case of squamous cell oesophageal carcinoma, dietary composition, smoking, alcohol and exposure to nitrosamines are major risk factors that may partly explain the disease's geographical distribution. The prognosis for oesophageal carcinoma is generally poor, due to the high incidence of distant metastasis and local recurrence. Combination treatment with both cisplatin and 5-fluorouracil is the most common chemotherapy regime used. We have carried out a detailed study of sensitivity of two oesophageal cell lines: OC1 cells from a squamous carcinoma of a male patient, and OC2, a squamous carcinoma obtained from a female patient. Both cell lines are sensitive to Vinca alkaloids and doxorubicin, while being quite resistant to alkylating agents such as cisplatin and 1,3-bis-(2-chloroethyl)-1-nitrosourea. This pattern of resistance suggests a possible role for glutathione S-transferase (GST) and/or glutathione (GSH) in resistance, and would seem to exclude the multidrug resistance phenotype. Both cell lines possess mainly Pi-class GSTs, and have distinct levels of GSH, with OC2 possessing some 25% of the level of OC1 cells. Effects of a variety of modulating agents on the pattern of resistance, such as the GSH depleter, buthionine sulphoximine, and the GST inhibitor, ethacrynic acid, were determined. An unexpected observation was that ethacrynic acid appears to increase the level of GSH in both cell lines.

Antineoplastic Agents↗

Workshop to implement the baby-friendly office initiative. Effect on community physicians' offices.

OBJECTIVE: To assess the effect of a self-appraisal questionnaire and a workshop for office staff in promoting the baby-friendly office (BFO). DESIGN: A two-times-three factorial design with a delayed workshop for one of two groups: an early intervention group who attended a workshop for office staff in October 1997 (n = 23) and a late-intervention group who attended in April 1998 (n = 23). Self-appraisals were completed before the workshops by all participants in October 1997, by 37 offices in April 1998, and by 34 offices in October 1998. SETTING: Offices of family physicians and primary care pediatricians in Hamilton-Wentworth, Ont. PARTICIPANTS: Staff of 46 offices; 74% (34/46) completed all three assessments. MAIN OUTCOME MEASURES: Degree of change in implementing each of the "10 Steps to Baby-Friendly Office" and overall average BFO score received by each office. RESULTS: Of the 34 offices completing all assessments, none followed all 10 steps. Initial mean score was 4.4 steps (standard deviation 1.4, n = 46). The workshop intervention improved overall mean scores from 4.3 to 5.6 (P < .001, n = 37). Although office staff completed the BFO self-appraisal tool, it alone had no effect on scores. Areas of improvement were noted in providing information to patients and displaying posters to promote breastfeeding. Key steps, such as not advertising breast milk substitutes and not distributing free formula, did not change. CONCLUSION: The workshop effected a modest but positive change in breastfeeding promotion. The change was maintained at 6 and 12 months after the intervention.

Adult↗

Variable expression of glutathione S-transferase isoenzymes in the fungus, Mucor circinelloides.

Mucor circinelloides (previously M. javanicus) variably expresses two isoenzymes of glutathione S-transferases. Glutathione S-transferases 1 and 2 were purified by affinity chromatography and found to be dimers with subunit M(r) values of 25.5 and 28. While glutathione S-transferase 1 immunoblotted with rat glutathione S-transferase T 5-5, N-terminal sequencing indicated that this enzyme was distinct from recently characterised bacterial and fungal glutathione S-transferases and did not readily fit into any one class. It showed some similarity to several classes including insect class II and plant type III. M. circinelloides glutathione S-transferase 2 did not immunoblot and yielded no N-terminal sequence.

Amino Acid Sequence↗

Micrometastases in esophagogastric cancer: high detection rate in resected rib segments.

BACKGROUND & AIMS: Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity. METHODS: In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18-positive cells. Viability and tumorigenicity were determined by culture and xenograft. RESULTS: Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice. CONCLUSIONS: Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

Adenocarcinoma↗

Effects of seasonality on xenobiotic and antioxidant defence mechanisms of bivalve molluscs.

Levels of chemical pollutants in the environment often display wide seasonal variation in response to climatic and other factors. Use of bioindicators such as enzyme activities in biomonitoring studies is complicated by this variation. Many such enzyme activities themselves show considerable seasonal fluctuation and there is known to be seasonality also in natural exposure to oxidative stress. This review attempts to explore some consequences of seasonal variation for biomonitoring studies with bivalve molluscs. It is suggested that independence of seasonal variation should be seen as a desirable feature of a bioindicator molecule. Where such molecules show seasonal variation, however, this should be incorporated into interpretation of biomonitoring studies by the use of appropriate controls.

Animals↗

Glutathione S-transferases of the yeast Yarrowia lipolytica have unusually large molecular mass.

Two similar glutathione S-transferases (GSTs), which do not bind to glutathione- or S-hexylglutathione-agarose affinity resins, have been purified from the yeast Yarrowia lipolytica. An approx. 400-fold purification was obtained by a combination of DEAE-Sephadex, phenyl-Sepharose, hydroxyapatite and Mono-Q anion-exchange chromatography. The native molecular mass of both proteins was estimated as approx. 110 kDa by both Superose-12 gel-filtration chromatography and non-denaturing electrophoresis. SDS/PAGE indicated a subunit mass of 50 kDa. Reverse-phase HPLC of purified proteins gave a single, well-resolved, peak, suggesting that the proteins are homodimers. Identical behaviour on HPLC, native electrophoresis and SDS/PAGE, N-terminal sequencing, sensitivity to a panel of inhibitors and identical specific activities with 1-chloro-2,4-dinitrobenzene as substrate suggest that the two isoenzymes are very similar. The enzymes do not immunoblot with antisera to any of the main GST classes, and N-terminal sequencing suggests no clear relationship with previously characterized enzymes, such as that of the fungus, Phanerochaete chrysosporium [Dowd, Buckley and Sheehan (1997) Biochem. J. 324, 243-248]. It is possible that the two isoenzymes arise as a result of post-translational modification of a single GST isoenzyme.

Amino Acid Sequence↗

Glutathione S-transferases from the white-rot fungus, Phanerochaete chrysosporium.

A glutathione S-transferase (GST) was purified to homogeneity from the white-rot fungus, Phanerochaete chrysosporium, by affinity chromatography on glutathione-agarose followed by Mono-Q ion-exchange FPLC. This protein immunoblotted with antisera to rat Theta class GST 5-5 and also showed N-terminal sequence similarity to the Theta class, including the presence of a conserved serine residue that has been specifically implicated in catalysis in this class [Wilce, Board, Feil and Parker (1995) EMBO J. 14, 2133-2143] and other residues conserved in plant sequences. Catalytic activity was found to be highly labile in the purified protein, although preliminary evidence for activity (approx. 120 m-units/mg) with 1,2-epoxy-3-(p-nitrophenoxy)propane was obtained in some preparations. The enzyme seems to be a dimer with a subunit molecular mass of 25 kDa by SDS/PAGE. The native molecular masses estimated by non-denaturing electrophoresis and by Superose-12 gel filtration were 58 and 45 kDa respectively. A second protein purified in this study also gave low level of activity with 1,2-epoxy-3-(p-nitrophenoxy)propane and had a subunit molecular mass of 28 kDa (native size 62-63 kDa), but did not immunoblot with any GST class and seemed to be N-terminally blocked.

Agaricales↗

Surface activity properties of cysteine-substituted C-terminal melittin analogues.

In order to extend our knowledge of factors important in the surface activity of melittin, cysteine was substituted for lysine-21 and lysine-21/glutamine-25 in a pair of synthetic peptide analogues. The first of these changes resulted in only modest effects on secondary structure (determined in 50% trifluoroethanol), emulsification and surface tension properties. Introduction of a second cysteine greatly reduced both the rate of surface tension decay and the equilibrium surface tension attained, although secondary structure (determined in 50% trifluoroethanol) was only slightly affected by this modification. This latter peptide completely lacked emulsification and haemolytic properties and was found to oligomerise readily due to the formation of intermolecular, disulphide bridges. These results indicate that oligomerisation abolishes surface activity in melittin.

Animals↗

A somatodendritic distribution of Rab11 in rabbit brain neurons.

Comparisons of subcellular targeting in neurons and epithelial cells have led to suggestions that apical epithelial antigens localize to axons and nerve terminals. We have studied the distribution in brain of the small GTP-binding protein, Rab11, which is localized to apical vesicular populations in epithelial cells. Sections of rabbit brain were examined by immunohistochemistry using a monoclonal antibody against rabbit Rab11. Rab11 immunoreactivity was present exclusively in neurons. In all regions examined, including forebrain, cerebellum, thalamus and brainstem, Rab11 immunoreactivity was observed in cell bodies and dendrites. No staining was observed in hippocampal neurons. These results indicate that the distribution of Rab11 does not support previous suggestions that apical epithelial markers should localize to axons and synaptic endings.

Animals↗

Binding of 2-hydroxy-5-nitrobenzyl alcohol to rat alpha class glutathione S-transferases; evidence for binding at tryptophan 21.

2-Hydroxy-5-nitrobenzyl alcohol (HNB) was prepared from dimethyl(2-hydroxyl-5-nitrobenzyl)sulfonium bromide (HNBB). HNB binds to glutathione S-transferases (GSTs) 1-2 and 2-2 with moderate affinity at a site separate from 1-anilino-8-naphthalenesulfonate (ANS). Intrinsic fluorescence due to Trp-21 is strongly quenched by HNB binding but there is no effect on catalytic activity. There appear to be two HNB binding sites per dimer in each GST isoenzyme. We suggest that HNB binds directly at Trp-21 of each subunit and that previously reported quenching of intrinsic fluorescence in these proteins upon ligand binding may be due to indirect structural effects rather than direct binding at this residue.

Anilino Naphthalenesulfonates↗

Occurrence of the Cys311 DRD2 variant in a pedigree multiply affected with panic disorder.

Following the detection of the rare DRD2 codon 311 variant (Ser-->Cys) in an affected member from a large, multiply affected panic disorder family, we investigated the occurrence of this variant in other family members. The variant occurred in both affected and unaffected individuals. Further screening in panic disorder sib pairs unrelated to this family failed to detect the Cys311 variant. Our data suggests that this variant has no pathogenic role in panic disorder.

Base Sequence↗