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Biomedical subjects

D J Curtis

Publications and source records attributed to D J Curtis.

At least 19 recordsLinked to original sources
PubMed2006

A re-evaluation of the role of vision in the activity and communication of nocturnal primates.

This paper examines the importance of vision in the lives of nocturnal primates in comparison to diurnal and cathemeral species. Vision is the major sense in all primates and there is evidence that the eyesight of nocturnal species is more acute and variable than has previously been recognized. Case studies of the behaviour of a galago and a loris in open woodland habitats in relation to ambient light show that Galago moholi males are more likely to travel between clumps of vegetation along the ground when the moon is up, and during periods of twilight, whereas they retreat to more continuous vegetation and travel less when the moon sets. This is interpreted as a strategy for avoiding predators that hunt on the ground when it is dark. The travel distances of Loris lydekkerianus are not affected by moonlight but this species reduces its choice of food items from more mobile prey to mainly ants when the moon sets, indicating the importance of light when searching for high-energy supplements to its staple diet. Evidence is presented for the first time to indicate key aspects of nocturnal vision that would benefit from further research. It is suggested that the light and dark facial markings of many species convey information about species and individual identity when animals approach each other at night. Differences in the colour of the reflective eye-shine, and behavioural responses displayed when exposed to white torchlight, point to different kinds of nocturnal vision that are suited to each niche, including the possibility of some degree of colour discrimination. The ability of even specialist nocturnal species to see well in broad daylight demonstrates an inherent flexibility that would enable movement into diurnal niches. The major differences in the sensitivity and perceptual anatomy of diurnal lemurs compared to diurnal anthropoids, and the emergence of cathemerality in lemurs, is interpreted as a reflection of evolution from different ancestral stocks in very different ecosystems, and not a recent shift towards diurnality due to human disturbance.

Animals↗
PubMed2006

The evolution of cathemerality in primates and other mammals: a comparative and chronoecological approach.

Non-primate mammalian activity cycles are highly variable across and within taxonomic groups. In contrast, the order Primates has historically been recognized as displaying a diurnal-nocturnal dichotomy that mapped, for the most part, onto the taxonomic division between haplorhines and strepsirhines. However, it has become clear over the past two decades that activity cycles in primates are not quite so clear cut. Some primate species--like many large herbivorous mammals, mustelids, microtine rodents, and shrews--exhibit activity both at night and during the day. This activity pattern is often polyphasic or ultradian (several short activity bouts per 24-hour period), in contrast to the generally monophasic pattern (one long bout of activity per 24-hour period) observed in diurnal and nocturnal mammals. Alternatively, it can vary on a seasonal basis, with nocturnal activity exhibited during one season, and diurnal activity during the other season. The term now generally employed to describe the exploitation of both diurnal and nocturnal phases in primates is 'cathemeral'. Cathemerality has been documented in one haplorhine, the owl monkey, Aotus azarai, in the Paraguayan and Argentinian Chaco and in several Malagasy strepsirhines, including Eulemur spp., Hapalemur sp. and Lemur catta. In this paper, we review patterns of day-night activity in primates and other mammals and investigate the potential ecological and physiological bases underlying such 24-hour activity. Secondly, we will consider the role of cathemerality in primate evolution.

Animals↗
PubMed2001

NF-Y regulates LIF-induced transcription of the signaling adaptor SKAP55R in myeloid cells.

Previously, we have shown that interleukin-6 (IL-6) or leukemia inhibitory factor (LIF)-induced differentiation of the myeloid cell line M1 was associated with a rapid increase in the level of mRNA encoding the signaling adaptor protein, SKAP55R. Furthermore, enforced over-expression of SKAP55R in primary bone marrow cells inhibited colony growth. In this study, we have identified the cis-acting elements that control SKAP55R transcription in myeloid cells. The 980 bp genomic sequence upstream of the transcriptional start site was cloned into a GFP reporter vector for transient (293 cells) or stable (M1 cells) transfection assays. This region contained cis-acting elements necessary for transcriptional activity in unstimulated 293 cells (10-fold higher levels than the control vector) or unstimulated M1 cells (two-fold higher levels). Significant LIF-induced transcription was observed in M1 (3.4-fold induction, P < 0.001), but not 293 cells. Deletion reporter constructs defined a promoter region (-317/-137) essential for the transcriptional activity in M1 cells. This region contained a CCAAT element recently implicated in IL-6/LIF-induced transcriptional regulation of junB in M1 cells. Mutation of the CCAAT element (-250/-246) significantly reduced both basal and LIF-induced transcription (P < 0.01). Electrophoretic mobility shift assays demonstrated that NF-Y bound to the CCAAT element of both SKAP55R and junB. These results suggest NF-Y binding may be a common mechanism of IL-6/LIF-regulated transcription in myeloid cells.

Animals↗
PubMed2000

Adaptor protein SKAP55R is associated with myeloid differentiation and growth arrest.

Activation of the SRC family of protein tyrosine kinases is an important component of intracellular signaling in hematopoiesis, but their critical substrates are less well understood. In this report, we describe the cloning and functional characterization of murine SKAP55R (mSKAP55R), an SRC family kinase substrate. Expression of mSKAP55R was examined by Northern blot. Phosphorylation of mSKAP55R was examined by transient transfection of COS cells. For overexpression studies, mSKAP55R was cloned into a bicistronic murine stem cell virus-based retrovirus. Transduced cells (FDC-P1 cell line and murine bone marrow) were FACS isolated by expression of the selectable marker green fluorescent protein.mSKAP55R showed 90% amino acid identity to the recently published human SKAP55R. mSKAP55R contained a central pleckstrin homology domain, a C-terminal SH3 domain, and a putative SRC kinase consensus substrate DEIY(260). mSKAP55R was expressed in all hematopoietic lineages, with relative mRNA levels greatest in cells of the myeloid and erythroid lineages. Induced myeloid differentiation of M1 and HL-60 cell lines was associated with an eight-fold increase in mSKAP55R mRNA. Transient expression of mSKAP55R in COS cells demonstrated that tyrosine 260 was the predominant site of phosphorylation by FYN kinase. Furthermore, this phosphotyrosine was essential for coimmunoprecipitation of FYN with mSKAP55R. Enforced expression of mSKAP55R inhibited in vitro growth of the myeloid FDC-P1 cell line and primary hematopoietic progenitors. In contrast, a tyrosine 260 mutant mSKAP55R had no effect on in vitro growth. These studies implicate mSKAP55R in the processes of myeloid differentiation and growth arrest.

Amino Acid Sequence↗
PubMed2000

Leukemic cells from murine myeloid leukemia display an intrinsic ability for autonomous proliferation.

OBJECTIVE: Human acute myeloid leukemia (AML) cells can proliferate in vitro in the absence of added growth factors when cultured at high cell density. Autocrine growth factor production is a postulated mechanism of autonomous growth. We sought to examine this using murine AML cells. MATERIALS AND METHODS: We have utilized a Moloney murine leukemia virus (M-MuLV) model of AML to investigate the nature of autonomous in vitro growth of myeloid leukemic cells. RESULTS: Like human AML, M-MuLV-induced myeloid leukemic cells displayed autonomous growth in unstimulated high cell density cultures. However, replating of individual, primary, growth factor autonomous colonies of leukemic cells demonstrated the presence of clonogenic cells capable of autonomous growth when cultured at low cell density. In addition, there was heterogeneity in the progeny of these cells: both factor-dependent leukemic cells and cells autonomous of exogenous factor were observed. CONCLUSION: We propose that clonogenic cells capable of autonomous growth at low cell density represent leukemic progenitors while the majority of leukemic cells derived from these "autonomous" leukemic cells are factor-dependent.

Acute Disease↗
PubMed2000

Non-invasive monitoring of reproductive status in wild mongoose lemurs (Eulemur mongoz).

Endocrine profiles were investigated in wild and captive mongoose lemurs (Eulemur mongoz; Lemuridae) by analysing faecal progestagens and oestrogens. Oestrous cycle characterization was not possible, as most females appeared to conceive during the first oestrus of the breeding season. Conception was preceded by a pseudo-oestrus with no discernible luteal phase. Pseudo-oestrus and oestrus identification was possible by investigating the oestrogen:progestagen ratio. Pregnancy was reliably determined approximately 47 days after conception, when progestagen and oestrogen excretion increased above breeding season concentrations. Gestation was further characterized by high progestagen concentrations and a decline in oestrogen excretion 70-80 days after conception. Post partum, progestagens declined, but oestrogen excretion increased to exceed breeding season concentrations. In the wild group, a nulliparous daughter conceived while still a member of her natal group and aborted after 70-80 days of pregnancy at which time progestagens had declined but oestrogens remained high. Comparisons with other strepsirhine primates suggest that pseudo-oestrus followed by conception at first oestrus may be prevalent in lemurs. Gestational progesterone profiles vary between species, but a delayed increase in oestrogens during pregnancy could be common to all strepsirhines, although oestrogen levels during the final trimester of pregnancy differ between lemurs and lorises. Methodological investigations showed that prolonged storage of faeces in ethanol is viable and that the presence of undigested vegetable matter in the faecal pellets had no effect on the interpretation of hormone profiles.

Animals↗
PubMed1999

Cathemerality in the mongoose lemur, Eulemur mongoz.

Results of a 10 month study of the mongoose lemur (Eulemur mongoz) at Anjamena are presented. The activity pattern is documented in detail for both wet and dry seasons based on observations conducted over the entire 24 h period. E. mongoz was found to be cathemeral throughout the year but exhibited shifts towards more diurnal activity in the wet season and more nocturnal activity in the dry season. The cathemeral activity pattern in the mongoose lemur appears to be coordinated with sunrise, sunset, and day length and modulated by an inhibitory effect of low nocturnal light intensity in the forest during the wet season, resulting in mainly diurnal activity. Temperature and rainfall may also influence the activity pattern. Few advantages to food-related behavior appear to derive from this activity pattern, although resource accessibility may be enhanced by nocturnal behavior in the dry season, leading to reduction in interspecific competition. Cathemerality may also represent a behavioral thermoregulatory mechanism allowing the mongoose lemur to conserve energy by being active during the cool nights of the dry season. In addition, nocturnal behavior in the dry season probably allows avoidance of predation by raptors at the time of year when least protection is afforded by vegetation.

Animals↗
PubMed1999

The addition of allogeneic peripheral blood-derived progenitor cells to bone marrow for transplantation: results of a randomised clinical trial.

BACKGROUND: The use of cytokine-mobilised peripheral-blood-derived progenitor cells (PBPC) has resulted in a significant improvement in the safety of autologous transplantation. Collections of PBPC contain large numbers of haemopoietic progenitors and T-lymphocytes when compared with bone marrow (BM). AIMS: To assess the clinical effects and safety of filgrastim-mobilised allogeneic PBPC, in particular whether PBPC would alter the kinetics of engraftment or the incidence and severity of graft-versus-host disease (GVHD). METHODS: Twenty-seven patients undergoing allogeneic transplantation were randomised to receive BM or BM supplemented by PBPC. Patients were conditioned with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. GVHD prophylaxis was with methotrexate and cyclosporin. Ganciclovir prophylaxis was administered to all cytomegalovirus seropositive patients. No haemopoietic growth factor was used after BMT. Donors of PBPC underwent a single, seven litre apheresis after four days of filgrastim, 10 microg/kg/day by subcutaneous injection. RESULTS: Donor toxicity was mild, with the most frequently reported being bone pain in the cytokine-treated donors. The patients transplanted with BM+PBPC received an eight-fold increase in CD3+ T-lymphocytes (1.65X 10(8)kg vs 0.22 x 10(8)/kg, p=0.04) and the cytokine product contained a median of 5 x 10(6) CD34+ cells/kg. BM+PBPC patients had more rapid engraftment of neutrophils to 0.5x 10(9)/L (17 days vs 19 days, p=0.02) and platelets to 50X 10(9)/L (22 days vs 35 days, p=0.04). BM megakaryocyte numbers were significantly enhanced at days 14 and 28 after BMT (both p=0.04), however platelet transfusions were not significantly different. The incidence, organ distribution, severity and time to onset of acute and chronic GVHD were not different between the treatment groups and there was no difference in overall survival or event-free survival. CONCLUSIONS: Allogeneic PBPC from HLA-identical siblings may speed engraftment of neutrophils and platelets without detrimental effects on GVHD or survival.

Adult↗
PubMed1997

The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice.

Abnormal expression of SCL (TAL-1/TCL5) occurs in the majority of paediatric cases of acute T-cell lymphoblastic leukemia (T-ALL). Unexpectedly however, transgenic mice carrying scl coupled to the human T-cell specific CD2 enhancer (CD2-scl) did not spontaneously develop T-cell lymphomas despite high levels of scl expression in their thymocytes. Analogous to other transgenic models of lymphomagenesis, it is likely that additional genetic abnormalities are required to cooperate with scl to trigger lymphomagenesis. Two possible candidates are the p53 and N-ras genes which are mutated in some cases of T-ALL, particularly in relapsed disease. Therefore, we examined lymphomagenesis in the progeny of CD2-scl mice crossed with N-ras transgenic mice or p53 deficient. Surprisingly, the frequency of lymphomas in the p53 nullizygous or N-ras transgenic mice was not enhanced by expression of the scl transgene. In fact, expression of scl in both genetic backgrounds paradoxically reduced the frequency of thymic lymphomas and, at least in the p53 nullizygous mice, shifted the pattern of organ involvement to the peripheral lymphoid organs. In contrast, CD2-scl transgene expression accelerated lymphomagenesis in p53 heterozygous mice. These data suggest that the collaborative effects of scl with N-ras or p53 vary according to the developmental stage of the T-cell.

Alleles↗
PubMed1997

Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist.

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.

Amino Acid Sequence↗
PubMed1995

Functional anatomy of the trunk musculature in the slow loris (Nycticebus coucang).

Lorisid locomotor and postural behaviour exhibits a number of features that distinguish it clearly from other primates. The comparative myological study of the trunk in the slow loris (Nycticebus coucang) and the squirrel monkey (Saimiri sp.) presented here reveals differences that are related to unique aspects of lorisid positional behaviour. While quadrupedal running and leaping requires flexion and extension of the spine, slow climbing quadrupedalism in lorisids depends on spinal lateral flexion and rotation. The contrasting development of the epaxial musculature in the two species dissected reflects these different requirements. Bipedal suspension is a common posture in the lorisids during which rotation and dorsiflexion of the head is made possible by the robustly developed deep, dorsal, cervical musculature. The long lower lever arm in the M. rectus abdominis may play a significant role in the ventroflexion required to regain a quadrupedal stance.

Abdominal Muscles↗
PubMed1995

Chronic airflow obstruction in long-term survivors of allogeneic bone marrow transplantation.

Prospective pulmonary function tests (PFTs) of 49 long-term survivors of identical sibling bone marrow transplants (BMT) were analysed. Eight (16%) developed a persistent pulmonary syndrome characterised by a late onset, cough and dyspnoea, hyperinflation or patchy infiltrates on plain radiography and episodic bacterial infections. The predominant PFT pattern was obstructive (reduced forced expiratory ratio, FER) with a variable restrictive component (reduced vital capacity, VC). When compared with the other 41 patients (controls), mean FER (53% absolute) and VC (73% predicted) were significantly lower at 12 months (P = 0.005). Graft-versus-host disease (GVHD) was the only identifiable risk factor (odds ration 7.1). Five of 7 patients compared with 4 of 31 controls tested at 3 months had an abnormal FER or maximum mid-expiratory flow rate (MMFR), but not VC, prior to the onset of symptoms (P = 0.015). Patients with mild to moderate disease (FER 50-70%) had stable pulmonary function while severe cases progressed despite immunosuppressive agents. Earlier recognition of this syndrome by a reduced FER or MMFR may allow the initiation of therapy at a potentially reversible stage.

Adult↗
PubMed1994

Positional behaviour in captive aye-ayes (Daubentonia madagascariensis).

The aye-aye shows numerous special features in its postcranial skeleton, partly in association with its unusual feeding habits and partly in association with locomotor specialisation connected with the possession of claws. This study examined the positional behaviour of 3 captive adult aye-ayes in order to throw light on these morphological specialisations. Locomotion was dominated by quadrupedal walking and climbing. Given the relatively large body size of aye-ayes, an unexpectedly high frequency of head-first descent was observed. This may provide an explanation for two characteristics of aye-ayes: robusticity of the shoulder girdle and high compressive and bending strengths of the humerus. Agile leaping was also observed, contrasting with previous reports that this species is characterised by slow, cautious movement. Specific morphological features that are shared with slow-moving lorisids may be attributable to a combination of frequent head-first descent and postural suspension.

Animals↗
PubMed1991

Radiologic recommendation for breast biopsy on screening mammography reports.

Radiologic reports on screening mammography findings often obligate breast biopsy. Ready recommendation for biopsy of nonpalpable lesions imaged by x ray is a conservative radiologic policy but is unsettling for patients and creates an imperative bind for surgeons. Like the decision to send the patient with right lower quadrant abdominal pain home rather than to the operating room, the diagnosis that requires clinical confidence and precision is nonappendicitis. Noncancer of the breast is a similar diagnosis that can usually be made on clinical and mammographic findings rather than passing such patients through to invasive diagnosis. A series of 84 patients was referred for needle localization of nonpalpable mammographically detected lesions called suspicious on screening examination. Of these 84 patients, new radiographic reports reinterpreting the findings without biopsy were written on the original mammogram in 15 patients. This is a cancellation rate of 21 per cent. In 69 patients needle localization was carried out with the finding of cancer in 28 per cent, compared with the national average of 15 per cent. This higher than average yield caused concern whether any unbiopsied cancers had been followed, and a review of these patients was undertaken. In the log of patients referred for needle localization, the prereading by the mammographer performing the needle localization was recorded in advance of biopsy confirmation, and specificity proved to be 94 per cent and sensitivity 96 per cent. Of the cancers that were detected, 39 per cent were proven in patients older than 50 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗
PubMed1989

Selecting radiology resident candidates.

Radiology resident candidate selection has become a burdensome, subjective, and somewhat arbitrary process. Because the luxury of many well-qualified candidates exists, there is an obligation to select them as honestly, equitably, and objectively as possible. Two years were spent in revising and modifying the resident selection process to make it more uniform and more efficacious. An application scoring form was devised to extract uniform pertinent information from the original application form. Candidates could then be ranked according to a numerical score derived from the form. This allowed easy selection of top candidates to be interviewed. A new interviewing scoring form was developed to include desirable characteristics of resident candidate performance. This form was also devised in such a way as to be easily scored and to allow selection of the top 20 to 25 candidates. These candidates were then ranked by participating faculty members while reviewing their application score forms and their interview forms. Positions for the residency training program were offered according to the ranking. The usefulness of both new forms was evaluated and confirmed by correlating form scores with faculty ranking of academic performance of current residents in the training program.

District of Columbia↗