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Biomedical subjects

D A Collins

Publications and source records attributed to D A Collins.

35 records · Page 2Linked to original sources
PubMed1995

Reproductive constraints on aggressive competition in female baboons.

Competitive interaction between females of same social group is characteristic of most primate species. In Old World monkeys, females of high social rank maintain priority of access to scarce resources and harass low-ranking companions. But different field studies have found differing correlations between female dominance and reproductive success: several populations show an advantage of rank whereas others do not. Although such variation may reflect divergent levels of predation, food availability or social stress in different environments, female competitive ability may also be balanced by significant reproductive costs and thus be subject to strong stabilizing selection. We report here that high-ranking female baboons (Papio cynocephalus anubis) at Gombe National Park, Tanzania, enjoy shorter interbirth intervals, improved infant survival, and accelerated maturation of their daughters. These advantages, however, are countered by a significantly higher probability of miscarriage, and a proportion of high-ranking females suffer from reduced fertility.

Abortion, Veterinary↗
PubMed1995

Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease.

Sulphasalazine is a commonly used second line agent in rheumatoid arthritis (RA) and other inflammatory joint diseases and is reported to be one of the least toxic of this group of drugs. Recently a severe allergic reaction and cases of lupus-like disease have been described in patients with RA after treatment with sulphasalazine. We describe five patients, all with inflammatory arthropathy who developed cutaneous vasculitis, lupus-like disease or atypical serology after exposure to sulphasalazine. Three of four cases investigated were found to have the slow acetylator phenotype. These reactions can complicate the diagnosis and delay discontinuation of the drug. Moreover, present guidelines for the diagnosis of drug-induced lupus do not apply to the majority of patients with sulphasalazine-induced lupus.

Adult↗
PubMed1995

Systemic vasculitis presenting with massive bowel infarction.

Gastrointestinal involvement in systemic vasculitis occurs in up to 30% of patients. Fortunately intestinal infarction is a rare complication, but if present carries a high mortality, and swift management of the underlying vasculitis is crucial. Two such cases are described.

Abdominal Pain↗
PubMed1995

Erythrocyte aplasia and systemic lupus erythematosus.

Pure erythrocyte aplasia is a recognised feature of systemic lupus erythematosus (SLE); here we report two cases, one predating the onset of SLE, the other following a long period of disease quiescence. One case demonstrates the typical features of this disorder and was successfully treated with prednisolone. The second case is unusual in being resistant to immunosuppressive treatment. Bone marrow culture from the second patient revealed an inhibition of BFU-E colony formation in the presence of the patient's serum, indicating that a serum inhibitor of haemopoiesis was present. Furthermore, following T cell depletion of this patient's marrow, there was an increase in BFU-E, CFU-G and CFU-GM colony growth implicating, in addition, a possible T cell-mediated inhibition of marrow haemopoiesis. This is a novel observation and may explain the resistance shown by this patient to standard treatment.

Adult↗
PubMed1993

The development of a bedside algorithm capable of targeting anti-endotoxins to the responder subpopulations.

The published selection criteria for use of anti-endotoxin antibodies are modeled on the criteria used in protocol enrollment of patients. These criteria are not suitable for therapeutic decision-making, because the trials themselves prove that the enrollment criteria have both low sensitivity and low specificity. In order to develop a selection method with greater sensitivity and specificity, we examined the charts and records of 23 patients that we enrolled in the multicenter trials of E5 and HA-1A. We retrospectively determined that seven of our 23 enrolled patients were optimal candidates, based on a pattern of rapid clinical deterioration followed by improvement in 24-96 h. We then explored a variety of different modes of bedside patient selection, in search of a method to select as many of the seven optimal candidates as possible while at the same time rejecting the greatest number of the 16 who showed no benefit when treated. None of the resulting selection methods has perfect performance, but nearly all were better than the original protocol enrollment criteria. In our patients, bacteremia had 57% sensitivity and 56% specificity, which was quite similar to the findings in the HA-1A multicenter trial. Shock had 100% sensitivity and 44% specificity, while a baseline organ dysfunction score of > or = 5 had 100% sensitivity and 69% specificity. A new algorithm that we developed based on a patient's need for vasopressors and baseline organ dysfunction had 100% sensitivity and 81% specificity. This algorithm could identify all seven of the optimal candidates, plus three more.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Prevalence of Helicobacter pylori infection and its effect on symptoms and non-steroidal anti-inflammatory drug induced gastrointestinal damage in patients with rheumatoid arthritis.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter (H pylori) are both associated with an increased risk of peptic ulceration and gastropathy. It is not known, however, if there is an interaction between these two agents, and thus whether or not screening for H pylori before NSAID treatment is of value. The aim of this study was to find out if H pylori potentiates the damaging effects of NSAIDs. Fifty two patients with rheumatoid arthritis requiring longterm NSAID treatment were studied. Dyspeptic symptoms were assessed according to a standardised questionnaire. Gastroscopy was performed after a one week washout period during which NSAIDs were discontinued. Gastric and duodenal mucosal damage was graded endoscopically. H pylori was identified by biopsy urease test and by histological tests. Investigations were repeated after one month's treatment with an NSAID. Patients with H pylori infection (n = 26) had a higher dyspeptic symptom score (p < 0.05). One patient with duodenal ulcer (H pylori +ve) and two with endoscopic gastritis (both H pylori +ve) were excluded from further study. Forty two subjects completed the study. After treatment there was a rise in the gastric damage score both in the H pylori +ve (p = 0.06) and the H pylori -ve (p < 0.005) groups. There was no difference in the extent of increase in grade or the final grade at the end of the treatment period between the H pylori +ve and -ve patients. It is concluded that H pylori infection is associated with increased dyspeptic symptoms in patients receiving NSAIDs but that it does not potentiate NSAID gastropathy.

Adult↗
PubMed1992

Derivation of osteoclasts from hematopoietic colony-forming cells in culture.

The osteoclast is known to be derived from the hematopoietic stem cell, but its lineage remains controversial. There is evidence that osteoclastic differentiation is induced through a contact-dependent interaction between bone marrow stromal cells and hematopoietic precursors. To analyze osteoclastic lineage, colonies were generated in semisolid medium from mouse spleen cells in the presence of Wehi-conditioned medium, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF) with or without erythropoietin (epo). After 5-8 days colonies were picked and phenotyped and incubated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on bone slices or coverslips with bone marrow-derived cell lines (ts8 or ST2) that induce osteoclastic differentiation. Cells of osteoclastic phenotype [as judged by calcitonin receptor (CTR) expression or bone resorption] were observed only in multilineage colonies. The ability of cells that generate macrophage colonies (CFU-M) to generate osteoclasts was tested by incubating alveolar or peritoneal macrophages on ts8 or ST2 cells. Despite colony formation, no osteoclastic differentiation was detectable. Last, individual cells from blast cell colonies were incubated (1 cell per culture well) on ts8 or ST2 cells in the presence of 1,25-(OH)2D3 and epo (to expose the lineage potential of the plated cell). We found CTR-positive (CTRP) cells in 6 of 66 macrophage colonies, 7 of 12 granulocyte-macrophage (GM) colonies, and 49 of 50 colonies containing multiple lineages other than GM colonies. No single-lineage CTRP colonies were observed. Although most macrophage colonies did not contain CTRP, no CTRP were observed in colonies from which macrophages were absent. These results suggest that osteoclasts are derived from a multilineage precursor rather than from CFU-M.

Animals↗
PubMed1992

Prostaglandin E2 promotes osteoclast formation in murine hematopoietic cultures through an action on hematopoietic cells.

Osteoclastic differentiation is induced from hematopoietic cells in the presence of 1,25-(OH)2D3 by stromal cells that are present in bone but not in hematopoietic spleen. Recent evidence suggests that prostaglandins (PGs) are essential for this process. In this communication we describe experiments in which we have examined further the role of PGE2 in osteoclast formation. We found a marked reduction in basal, 1,25-(OH)2D3, and IL-3-induced production of calcitonin receptor (CTR)-positive cells and bone resorption by cyclooxygenase inhibitors, which was restored by PGE2 addition. Although some stromal cell types (ST2 cells) that support osteoclast formation from spleen cells produced PGs in response to 1,25-(OH)2D3, others (ts8 and calvarial cells) did not, either alone or in combination with spleen cells. On the other hand, both bone marrow and spleen cells produced amounts of PGE2 in response to 1,25-(OH)2D3 that were sufficient to account for osteoclast formation. Osteoclast-inductive ts8 cells were able to support osteoclast formation from spleen cells in the presence of 1,25-(OH)2D3 or PGE2 even if devitalized. Incubation of ts8 cells in these agents before devitalization did not avoid the requirement for the presence of PGE2 or 1,25-(OH)2D3 during subsequent incubation with spleen cells. Thus, hematopoietic cells produce sufficient PGE2 for osteoclast formation, and the PGE2 thus produced acts on hematopoietic precursors, which can be induced in the presence of PGE2 to express CTR and resorb bone on contact with osteoclast-inductive stromal cells. The ability of osteoclast-inductive cells to support osteoclast formation appears not to rest on their ability to produce, induce, or respond to PGE2.

Animals↗
PubMed1992

An assessment of the ability of human bone marrow cultures to generate osteoclasts.

Several groups have successfully generated osteoclasts in cultures of murine haemopoietic cells. This approach would clearly be useful in the analysis of mechanisms of regulation of human osteoclast formation if analogous results could be obtained in cultures of human bone marrow. This communication describes independent attempts by three groups to generate unequivocally defined osteoclasts from bone marrow obtained from human iliac crest, femoral neck, rib, and from foetuses. The haemopoietic tissue was incubated using techniques described by others for production of osteoclast-like cells, and with variants of this technique using strategies based on our experiences with murine osteoclastogenesis. Haemopoietic cells were incubated with calcium regulating hormones, cytokines, osteoblastic supernatants, and osteoblastic or bone marrow stromal cell layers. Formation of cells capable of excavation of bone slices was rarely seen. Despite the paucity of bone resorbing cells, multinucleate cells (MNCs) developed with similar characteristics to the MNCs that have been interpreted as osteoclast-like in human bone marrow cultures. The MNCs were, however, calcitonin-receptor (CTR) negative, and did not show the typical pattern of reactivity with osteoclast-specific antibodies. They possessed instead an antigenic profile characteristic of macrophage polykaryons. We conclude that the MNCs which consistently generate in human bone marrow cultures do not possess phenotypic characteristics specific for osteoclasts and appear to be macrophage polykaryons. The conditions required for osteoclast generation in cultures of human haemopoietic cells remain to be defined.

Bone Marrow Cells↗
PubMed1991

Effect of prostaglandins E1, E2, and F2 alpha on osteoclast formation in mouse bone marrow cultures.

Prostaglandins (PG) act as direct inhibitors of mature osteoclasts, but although resorption-inhibition is also observed initially PG increase bone resorption in organ culture. This suggests that PG influence bone resorption in organ culture through actions on cell types other than mature osteoclasts. We have therefore tested the effects of PG E1, E2, and F2 alpha on the differentiation of osteoclastic phenotype in mouse bone marrow cultures using bone resorption and calcitonin receptors (CTR) as markers of osteoclastic differentiation. We found that PGE2 (10(-6)-10(-9) M) and PGE1 (10(-6)-10(-7) M) induced a significant increase in CTR-positive cell numbers, to levels five to eight times those seen in controls and similar to the number induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone resorption was increased (10(-7) M PGE2 and 10(-6) M PGE1) in association with the increased CTR-positive cell numbers, suggesting that the PG also induced resorptive function. 1,25-(OH)2D3 increased both the number of CTR-positive cells and the extent of resorption per cell; the additional presence of PG did not affect the number of CTR-positive cells but did reduce bone resorption compared with 1,25-(OH)2D3 alone. PGF2 alpha had no significant effect on CTR-positive cell induction or bone resorption. The results suggest that PGE1 and E2 induce osteoclastic differentiation in mouse bone marrow cultures and inhibit the function of the osteoclasts thus formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1990

Identification of four brain areas each enriched in a unique muscarinic receptor subtype.

The affinities of muscarinic agonists and antagonists were determined by autoradiography and image analysis in selected areas of the rat brain. IC50 values and Hill coefficients for the inhibition of the binding of 0.2 nM [3H]-QNB to dentate gyrus, superior colliculus, rhomboid thalamus and substantia nigra were measured in coronal sections. Pirenzepine displayed a high affinity for receptors in the dentate gyrus and AF-DX 116, the superior colliculus. Both pirenzepine and AF-DX 116 had high affinities for the substantia nigra and low affinities for the rhomboid thalamus. Gallamine displayed a 50-fold preference for superior colliculus over dentate gyrus receptors. Amitriptyline was less selective, showing a modest preference for substantia nigra receptors and 4-DAMP was essentially nonselective. Carbachol was the most selective agonist with a 4000-fold preference for superior colliculus over dentate gyrus receptors. Other agonists except RS 86 were also selective for superior colliculus receptors in the order carbachol much greater than arecoline greater than bethanechol greater than McN A343 = oxotremorine = pilocarpine.

Animals↗