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Biomedical subjects

D Rose

Publications and source records attributed to D Rose.

At least 19 recordsLinked to original sources

Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell responsiveness and spleen cellularity.

Isobutyl nitrite is an inhalant abused principally by male homosexuals. We have reported that subchronic inhalation exposure (45 min/day for 14 days) to 900 ppm isobutyl nitrite was immunosuppressive. In the present study, the effects of acute exposure to the inhalant were examined. Mice were exposed in an inhalation chamber to 900 ppm isobutyl nitrite for 45 min. One day later, spleen cellularity was reduced by 39% without selectively depleting CD4(+) or CD8(+) cells. The numbers of peripheral blood leukocytes and peritoneal cells were also reduced. Following acute inhalation exposure, T cell proliferative responses stimulated with allogeneic cells or anti-CD3 and anti-CD28 antibodies were inhibited, while mitogen-induced responses were not affected. Purified T cells exposed to the inhalant also had compromised responses, suggesting a direct effect on T cells. However, the cumulative effects of multiple exposures were necessary to inhibit T-dependent antibody responses or T cell or macrophage cytotoxicity.

Administration, Inhalation↗

Synaptic target recognition at Drosophila neuromuscular junctions.

Every synaptogenesis begins with "synaptic target recognition," a cell-cell recognition event in which a neuron and its target stably adhere. Despite its importance in developing nervous systems, synaptic target recognition has been difficult to study in complex systems. The relatively simple and genetically accessible Drosophila NMJ model system provides a repertoire of target recognition cues. We describe how these molecules control the targeting of specific growth cones in either a positive (synaptogenic) or negative (anti-synaptogenic) manner. We also propose two alternate signaling paradigms to explain how these initial cell recognition events are coupled to the intracellular signaling pathways that begin the process of synapse maturation.

Animals↗

Cytology of thymomas: emphasis on morphology and correlation with histologic subtypes.

BACKGROUND: Aspirates of thymomas are distinguishable from other lesions and fine-needle aspiration (FNA) is a proven method for investigating mediastinal masses. METHODS: Thirty-four cytology specimens of thymomas from 31 patients were examined. Corresponding surgical materials were available in 32 cases. Ten cases were benign and 22 were malignant. Cytologic features of these thymomas were correlated with various histologic classification systems and with biologic behavior. Dual epithelial and lymphoid populations and irregular cohesive tissue fragments of varying proportions of lymphoid and epithelial cells were characteristic of all aspirates. RESULTS: Using the Lattes-Bernatz classification, 10 cases predominately were lymphocytic, 3 cases predominately were epithelial, 3 cases predominately were spindle, 15 cases predominately were mixed, and 1 case was a thymic carcinoma. In the Muller-Hermelink classification, 3 cases were medullary, 12 were mixed, 8 predominately were cortical, 2 were cortical, 6 were well differentiated thymic carcinoma, and 1 was a poorly differentiated thymic carcinoma. In the majority of the cases the epithelial cells were round to oval. Spindle cells and a mixture of round to oval and spindle cells also were observed. No cytologic feature was found to correlate significantly with any classification scheme. Necrosis was present in 5 of the 32 aspirates, most frequently in malignant tumors. Thymomas showing predominately spindle cells frequently were encapsulated. Tumors with predominantly round to oval cells or a mixed population behaved more aggressively than those with spindle cells. Tumors that were well encapsulated and benign clinically tended to possess benign-appearing nuclei. Among the 22 invasive or malignant lesions, 8 exhibited moderate to marked cytologic atypia and 14 showed little or no atypia. No atypia was observed in benign tumors. CONCLUSIONS: The presence of cytologic atypia of epithelial cells may be helpful in predicting aggressiveness. However, the absence of atypia and necrosis may not imply a benign course. Correlation with clinical and radiographic findings should be sought.

Adult↗

The ultrastructural interactions of identified pre- and postsynaptic cells during synaptic target recognition in Drosophila embryos.

During the development of neural networks, what sets synaptogenic interactions apart from nonsynaptogenic interactions is not well understood at the subcellular level. Using a combination of intracellular dye injection and electron microscopy, we show that a specific motoneuron (RP3) and its synaptic partners (muscles 6 and 7), both often bearing microprocesses, develop intimate membrane contact sites characterized by junctional structures, prior to their initiating synaptogenesis in Drosophila embryos. Other motoneuron growth cones that extend alongside the RP3 growth cone to innervate surrounding muscles do not form such contacts with muscles 6 and 7. We also examined how specific target recognition molecules affect the development of these ultrastructural associations between synaptic partner cells. When Fasciclin III (Fas3), a "positive" target recognition molecule for RP3, is ectopically expressed in neighboring muscles, the RP3 growth cone ectopically develops membrane contact sites with Fas3-misexpressing muscles with which it would not normally associate. In contrast, when Toll, a "negative" target recognition molecule normally expressed by a subset of muscles that surrounds muscles 6 and 7, is misexpressed on muscles 6 and 7, the RP3 growth cone fails to exhibit its normal close contact with these muscles. We propose that the formation of close membrane associations and junctional structures can be regulated under the influence of synaptic target recognition molecules and signifies the beginning of subcellular events during synaptic target recognition.

Animals↗

Cognitive-behaviour therapy as a treatment for irritable bowel syndrome: a pilot study.

OBJECTIVE: The irritable bowel syndrome (IBS) is a chronic and often disabling functional bowel disorder. Psychological treatments, in particular cognitive and behavioural interventions, have been shown to be effective for this disorder. The aim of this study was to test the efficacy of a cognitive-behaviour program. METHOD: Eight participants (seven female, one male) aged between 24 and 71 years, with a diagnosis of IBS according to the Rome criteria, were recruited from among the gastroenterology outpatients at Nepean Hospital, in Sydney, Australia. Participants were administered pretreatment on measures of psychological function and bowel symptom severity. Following a 2-week baseline period, participants began a structured psychological treatment comprising eight sessions of cognitive-behaviour therapy. Throughout treatment, participants maintained daily records of symptom severity and completed homework assignments to ensure treatment compliance. The pretreatment assessment measures were repeated 1 week post-treatment. RESULTS: After treatment, five of the eight patients no longer met the Rome diagnostic criteria for IBS. There was no significant reduction in bowel symptom frequency. There were, however, significant improvements in the distress and disability associated with bowel symptoms. Anxiety and depression were also significantly reduced. CONCLUSIONS: Cognitive-behaviour therapy reduced the distress and disability associated with IBS, but not the frequency of bowel symptoms. This supports the proposed cognitive model for IBS, and cognitive-behaviour therapy appears to have its effect by altering the cognitive response to visceral hypersensitivity.

Adult↗

Superior labrum anterior-posterior lesions: diagnosis with MR arthrography of the shoulder.

PURPOSE: To determine the accuracy of magnetic resonance (MR) arthrography in the diagnosis of superior labrum anterior-posterior (SLAP) lesions of the shoulder. MATERIALS AND METHODS: From January 1995 to June 1998, MR arthrography of the shoulder was performed in 159 patients with a history of chronic shoulder pain or instability. Fifty-two patients underwent arthroscopy or open surgery 12 days to 5 months after MR arthrography. Diagnostic criteria for SLAP lesion included marked fraying of the articular aspect of the labrum, biceps anchor avulsion, inferiorly displaced bucket handle fragment, and extension of the tear into the biceps tendon fibers. Surgical findings were correlated with those from MR arthrography. RESULTS: SLAP injuries were diagnosed at surgery in 19 of the 52 patients (37%). Six of the 19 lesions (32%) were classified as type I, nine (47%) as type II, one (5%) as type III, and three (16%) as type IV. MR arthrography had a sensitivity of 89% (17 of 19 patients), a specificity of 91% (30 of 33 patients), and an accuracy of 90% (47 of 52 patients). The MR arthrographic classification showed correlation with the arthroscopic or surgical classification in 13 of 17 patients (76%) in whom SLAP lesions were diagnosed at MR arthrography. CONCLUSION: MR arthrography is a useful and accurate technique in the diagnosis of SLAP lesions of the shoulder. MR arthrography provides pertinent preoperative information with regard to the exact location of tears and grade of involvement of the biceps tendon.

Adult↗

HyCoSy--as good as claimed?

Hysterosalpingo contrast sonography (HyCoSy) has been compared favourably in the literature with hysterosalpingography (HSG). It does not require ionizing radiation and demonstrates the uterus and ovaries. HyCoSy is reported as being a safe, well tolerated, quick and easy investigation of Fallopian tube patency. Over a 1-year period HyCoSy was performed by two operators on 118 consecutive women who were thought likely to have patent Fallopian tubes. The examinations were graded using a local scale to assess discomfort and were correlated with tubal patency. HSG was performed on 116 patients by the same operators and discomfort recorded. 15 patients underwent both examinations. The degree of pain or reaction was graded 0 (no pain) to 4 (maximum) according to a locally devised scale. Costs of the two examinations were estimated. 89 patients examined by HyCoSy were graded 0-2. However, 23 had severe protracted pain and/or vasovagal reactions with bradycardia and hypotension. Of these, seven required resuscitation owing to prolonged symptoms, requiring treatment with atropine. 19 of the 23 had bilaterally patent Fallopian tubes. Where subsequent HSG was performed, tubal occlusion was confirmed in 8 of 15 women. Other pathologies were noted in 29 of the HyCoSy patients and there were six technical failures. During the same period no severe adverse reactions occurred in 116 patients having HSG performed by the same operators. Three of the HSG examinations were technically unsuccessful. Discomfort following HyCoSy was much greater than that reported previously. Possible mechanisms are discussed but it does not appear to be related to tubal occlusion. Diagnostic accuracy, costs and discomfort compare unfavourably with HSG.

Fallopian Tube Patency Tests↗

An integrated program for evidence-based medicine in medical school.

To provide optimal care for their patients, clinicians must be able to locate and interpret the most current literature. Teaching the necessary skills to medical students is essential, if we wish to train clinicians to be able to keep up with the expansion of biomedical knowledge for their entire working lives. In this paper, we describe our school's four-year curriculum in evidence-based medicine and the performance of three senior classes on the summative evaluation exercise devised to measure the program's success.

Curriculum↗

A single growth cone is capable of integrating simultaneously presented and functionally distinct molecular cues during target recognition.

A variety of cell recognition pathways affect neuronal target recognition. However, whether such pathways can converge at the level of a single growth cone is not well known. The RP3 motoneuron in Drosophila has previously been shown to respond to the muscle cell surface molecules TOLL and fasciclin III (FAS3), which are normally encountered during RP3 pathfinding in a sequential manner. TOLL and FAS3, putative "negative" and "positive" recognition molecules, respectively, affect RP3 antagonistically. Under normal conditions, TOLL and FAS3 together improve the accuracy of its target recognition. Here, we show that, when presented with concurrent TOLL and FAS3 expression, RP3 responds to both, integrating their effects. This was demonstrated most succinctly by single cell visualization methods. When a balance in relative expression levels between the two antagonistic cues is achieved, the RP3 growth cone exhibits a phenotype virtually identical to that seen when neither TOLL nor FAS3 is misexpressed. Thus, growth cones are capable of quantitatively evaluating distinct recognition cues and integrating them to attain a net result, in effect responding to the "balance of power" between positive and negative influences. We suggest that the ability to integrate multiple recognition pathways in real-time is one important way in which an individual growth cone interprets and navigates complex molecular environments.

Animals↗

Microdispensing technologies in drug discovery.

Because of the advent of managed care,the pharmaceutical industry is entering a new era, characterized by increased competition and pricing pressures. As a result, drug discovery within pharmaceutical companies is rapidly embracing new paradigms to help bring more novel drugs to the market as rapidly as possible. One paradigm currently being pursued is the miniaturization of the processes involved in the exploratory phase of drug discovery. This reduction in scale has led to the development of new dispensing technologies. This review examines several microdispensing technologies for drug discovery.

Journal Article↗

Central effects of 5-HT on respiratory rhythm in newborn rats in vivo.

The role of 5-HT in inducing apnoeas (a major element in sudden infant death syndrome) is controversial because while 5-HT is a respiratory depressant in vivo, it evokes respiratory analeptic effects when applied to the isolated brainstem of the newborn rat. In decerebrate newborn rats, the electrical activity of the diaphragm and that of a hypoglossally innervated tongue muscle, as well as the cardiac frequency (Fc), were recorded before and after the application of 5-HT and related agents to the floor of the IVth ventricle. To assess the spontaneous variability in inspiratory frequency (Fi) and Fc, a sham group was studied. A decrease in Fi was observed in response to 5-HT. This respiratory depressant effect was associated with an activation of the tongue muscle, but there was no change in Fc. Application of agonists elicited a small increase in Fi linked to activation of 5-HT1A receptors, and decreases in both Fi and the activity of the tongue muscle resulting predominantly from activation of 5-HT2 receptors. The decrease in Fi was much smaller in newborn rats than that reported in newborn kittens. Indeed, in newborn rats, we did not observe long-lasting apnoeas. Our results differ from those obtained from the newborn rat in vitro, inasmuch as in vivo 5-HT essentially depressed the respiratory rhythm generator. The role of the afferent system appears to be crucial in modulating the action of 5-HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Binocular and monocular detection of Gabor patches in binocular two-dimensional noise.

Contrast thresholds for detecting sine-wave Gabor patches in two-dimensional externally added random-pixel noise were measured. Thresholds were obtained for monocular and binocular signals in the presence of spatial correlated (identical) and uncorrelated (independent) noise in the two eyes. Measurements were obtained at four different spectral densities of noise (including zero). Thresholds were higher for monocular stimuli than for binocular, and higher in the presence of correlated noise compared to uncorrelated noise. The magnitude of binocular summation, similar in correlated and uncorrelated noise, decreased with increasing noise strength. The independent contributions of internal noise and sampling efficiency to detection were analysed. Sampling efficiencies were higher for binocular than for monocular viewing for both types of noise, with values being higher with uncorrelated noise. Binocular stimuli showed a lower equivalent noise level compared to the mean monocular case for both types of noise.

Contrast Sensitivity↗

The historical roots of the theories of local signs and labelled lines.

The theories of labelled lines and local signs are commonly invoked to explain numerous perceptual phenomena. These theories postulate that perceptual systems use information about which nerve cells or which information channels are activated by the stimulus. The origins of this idea in nineteenth century German psychophysics are traced. From Descartes's idea of a dualistic mind, Kant's idea of a mental ability to conceive space, Da Vinci's ideas of pictorial 'signs', and Müller's idea of 'specific nerve energies' to explain perceptual qualities, Steinbuch, Lotze, and others derived the conclusion that neural-level signs exist that signal stimulus location to the mind. Helmholtz, Hering, and others soon suggested variations on this basic idea. By the time of James the theory had changed yet again. It was revived elsewhere in the 1920s and again in the 1970s, although used implicitly by many workers in between and since. Against a modern metaphysical background, however, a distinction between labels (hardware) and signs (symbols) is the minimum step needed towards an appropriate and comprehensive explanation of perceptual behaviour and experience.

History, 19th Century↗

Economic determinants and dietary consequences of food insecurity in the United States.

This paper reviews recent research on the economic determinants and dietary consequences of food insecurity and hunger in the United States. The new Current Population Study (CPS) food insecurity and hunger measure shows that hunger rates decline sharply with rising incomes. Despite this strong relationship, confirmed in other national datasets, a one-to-one correspondence between poverty-level incomes and hunger does not exist. In 1995, 13.1% of those in poverty experienced hunger and half of those experiencing hunger had incomes above the poverty level. Panel data indicate that those who are often food insufficient are much more likely than food-sufficient households to have experienced recent events that stress household budgets, such as losing a job, gaining a household member or losing food stamps. Cross-sectional work also demonstrates the importance of food stamps because benefit levels are inversely related to food insufficiency. Concern for the dietary consequences of domestic food insufficiency is well placed; recent research shows that the odds of consuming intakes <50% of the recommended dietary allowance (RDA) are higher for adult women and elderly individuals from food-insufficient households. Preschoolers from food-insufficient households do not consume significantly lower amounts than those from food-sufficient households, but mean intakes for the rest of members in those very same households are significantly lower for the food insufficient. This research highlights the importance of food insecurity and hunger indicators, further validates the use of self-reported measures and points to areas of need for future research and interventions.

Adult↗

Emotions and psychopathology.

Few psychological assessment instruments exist for Jamaicans. Studies that address the appropriateness of foreign instruments for Jamaicans are sparse and empirical focus on psychopathology and its aetiology in Jamaican adults is virtually nonexistent. The present study addressed these deficits via Confirmatory Factor Analyses (CFA) which revealed that factors on the Toronto Alexithymia Scale (TAS-20) and Brief Symptom Inventory (BSI) were not replicated for a Jamaican sample (N = 352). Exploratory Factor Analyses (EFA) on the TAS-20 revealed one factor labelled Unawareness and Confusion Regarding Emotions (UCRE). Also, EFA yielded six BSI dimensions labelled Somatic Complaints, Paranoia, Hostility, Mild Depression/Dysthymia, Major Depression with Psychotic Features, and Agoraphobia with Panic. Regression analyses on the Jamaican-based TAS-20 and BSI factors revealed a positive relationship between UCRE and each BSI factor and total BSI score. Mild Depression, Agoraphobia with Panic, Paranoia, Hostility, Mild Depression and Major Depression were higher for women and younger Jamaicans, respectively, but younger Jamaicans with higher UCRE scores had higher scores on Paranoia, Major Depression, and total score. The findings suggest that Jamaican mental health policy and programmes should focus on the difficulties some Jamaicans experience in recognising and expressing their emotions.

Adolescent↗

A nematode kinesin required for cleavage furrow advancement.

Dividing cells need to coordinate the separation of chromosomes with the formation of a cleavage plane. There is evidence that microtubule bundles in the interzone region of the anaphase spindle somehow control both the location and the assembly of the cleavage furrow [1-3]. A microtubule motor that concentrates in the interzone, MKLP1, has previously been implicated in the assembly of both the metaphase spindle and the cleavage furrow [4-6]. To gain insight into mechanisms that might underlie interdependence of the spindle and the cleavage furrow, we used RNA-mediated interference (RNAi) to study the effects of eliminating MKLP1 from Caenorhabditis elegans embryos. Surprisingly, in MKLP1(RNAi) embryos, spindle formation appears normal until late anaphase. Microtubule bundles form in the spindle interzone and the cleavage furrow assembles; anaphase and cleavage furrow ingression initially appear normal. The interzone bundles do not gather into a stable midbody, however, and furrow contraction always fails before complete closure. This sequence of relatively normal mitosis and a late failure of cytokinesis continues for many cell cycles. These and additional results suggest that the interzone microtubule bundles need MKLP1 to encourage the advance and stable closure of the cleavage furrow.

Animals↗

Motion perception: from phi to omega.

When human observers view dynamic random noise, such as television 'snow', through a curved or annular aperture, they experience a compelling illusion that the noise is moving smoothly and coherently around the curve (the 'omega effect'). In several series of experiments, we have investigated the conditions under which this effect occurs and the possible mechanisms that might cause it. We contrast the omega effect with 'phi motion', seen when an object suddenly changes position. Our conclusions are that the visual scene is first segmented into objects before a coherent velocity is assigned to the texture on each object's surface. The omega effect arises because there are motion mechanisms that deal specifically with object rotation and these interact with pattern mechanisms sensitive to curvature.

Humans↗

"Painting" the target: how local molecular cues define synaptic relationships.

A majority of studies on neuronal growth cones focus on the features that particular groups of neurons share. In contrast, questions such as how specific growth cones respond very differently to the same extrinsic cues require cell-specific experimentation. The most succinct cell-specific growth cone responses occur during synaptic targeting. Recent studies have examined one specific growth cone, the Drosophila RP3 motoneuron growth cone, in variously altered microenvironments. In this review, we summarize how such studies are beginning to uncover the repertoire of extrinsic cues that influence the synaptic targeting of a single growth cone.

Animals↗