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Biomedical subjects

D Wise

Publications and source records attributed to D Wise.

At least 73 records · Page 4Linked to original sources

A community-based study of diabetes-related skills and knowledge in elderly people with insulin-requiring diabetes.

An open cross-sectional study of elderly (age greater than 65 yr) patients with insulin-requiring diabetes mellitus (n = 57) was undertaken to audit safety of self-management. Levels of knowledge and management skills of hypoglycaemia, hyperglycaemia, and foot care were determined. The prevalence of hypoglycaemia, visual impairment, and at-risk feet and the ability to perform practical procedures (insulin injection and self-monitoring) were assessed. Drawing up insulin and self-injection was correct in 84% and 76% of patients, but 53% of self-monitored urine or blood tests were performed incorrectly. Twenty-six per cent experienced hypoglycaemia at least monthly and 25% had been seen at the hospital with hypoglycaemia in the last year. Eighteen per cent did not know what action to take with hypoglycaemia. Forty-six per cent did not know any hyperglycaemic symptoms or signs. Prompted with symptoms, 35% still did not know what to do and 21% would take inappropriate action when self-monitored tests read high. Fifty-one per cent had impaired vision, 61% peripheral neuropathy and 24% peripheral vascular disease, with the result that 78% had at-risk feet. Fifteen percent inspected or washed their feet infrequently, 40% walked barefoot occasionally, and 47% would take potentially dangerous action in the event of foot injury. This study demonstrates serious deficiencies in the basic education and management skills in our elderly insulin-requiring diabetic population that could result in morbidity and mortality. Greater effort and vigilance by health care professionals must be directed towards this group.

Aged↗

Strategies for faculty practice.

Nursing faculty who prepare students for advanced roles in primary care are faced with maintaining their own clinical knowledge and skills at a time when doctoral preparation, research and scholarship are receiving emphasis. This article describes some successful faculty experiences in increasing clinical knowledge and practice while integrating clinical practice into the faculty role.

Clinical Competence↗

University-industry research relationships in biotechnology: implications for the university.

The growth of university-industry research relationships in biotechnology has raised questions concerning their effects, both positive and negative, on universities. A survey of over 1200 faculty members at 40 major universities in the United States reveals that biotechnology researchers with industrial support publish at higher rates, patent more frequently, participate in more administrative and professional activities and earn more than colleagues without such support. At the same time, faculty with industry funds are much more likely than other biotechnology faculty to report that their research has resulted in trade secrets and that commercial considerations have influenced their choice of research projects. Although the data do not establish a causal connection between industrial support and these faculty behaviors, our findings strongly suggest that university-industry research relationships have both benefits and risks for academic institutions. The challenge for universities is to find ways to manage these relationships that will preserve the benefits while minimizing the risks.

Antibodies, Monoclonal↗

Industrial support of university research in biotechnology.

A 1984 study of biotechnology companies reveals that nearly one-half of all such firms fund research in universities. Industry may support as much as one-quarter of all biotechnology research in institutions of higher education. These investments seem to be yielding substantial benefits to involved firms. Per dollar invested, university research is generating more patent applications than is other company research. Research relationships do pose some risks to traditional university values such as openness of communication among scholars. These risks may be greater in relationships involving small firms. The data also reveal that government is now, and seems likely to remain, the principal source of support for university research in biotechnology.

Industry↗

Specific disruption of spatial behaviour in rats by central muscarinic receptor blockade.

Three groups of rats were required to locate a single water bottle from an octagonal array of eight otherwise empty bottles. For one group (place navigation) the goal bottle remained in the same place from trial to trial; for a second group (cue navigation) the position of the goal bottle was cued by a black card over the nozzle; for the third group the goal bottle was uncued and moved randomly from trial to trial. Place and cue groups improved more than controls on all measures of performance. Scopolamine (0.2 mg/kg) substantially impaired performance in the place group, but had no effect on either of the other groups; the peripherally acting anticholinergic drug meth-scopolamine (0.2 mg/kg) had no effect in any group. In a second experiment, using food rewards, scopolamine caused a dose-dependent impairment of place navigation at doses from 0.025 to 0.4 mg/kg; 0.4 mg/kg also impaired cue navigation, but at this dose behaviour was visibly abnormal. In both experiments, scopolamine primarily affected speed of performance rather than accuracy. Olfactory cues were shown not to contribute to performance in either group. The results implicate central cholinergic transmission in the processing of visuo-spatial information.

Animals↗

A calcium-rich intraspindle membrane system in spermatocytes of wolf spiders.

The meiotic spindle of spermatocytes of two wolf spiders contains a highly organized system of ER-like membranes. In cells observed ultrastructurally at early prometaphase, these membranes completely invest each bivalent and are present in the periphery of the spindle in association with the centrosomes. By metaphase each bivalent and its kinetochore fibers are completely encased in a tube of this membrane. We have treated living spermatocytes with the permeant, fluorescent-chelate probe, chlorotetracycline (CTC) to determine whether or not the intraspindle membrane system is rich in associated Ca2+. Spider testes were dissected into PIPES-buffered saline containing 200 microM CTC and were kept in this solution for 10 min. Autofluorescence controls were prepared by incubation in saline without CTC, and nonspecific effects of CTC were assessed by incubation for 10 min in 200 microM oxytetracycline (OTC). Neither unstained nor OTC-treated spermatocytes emit significant fluorescence. In contrast, CTC treatment yields bright, punctate fluorescence, which coincides with the distribution of the mitochondria. The plasma membrane is only weakly fluorescent, while the nuclear envelope exhibits prominent fluorescence. The chromosomes are not fluorescent during prophase, but after nuclear envelope breakdown, they become outlined by dim, but distinct fluorescence. As spindle formation commences, the CTC signal from the intraspindle membrane system becomes strong. In some cells, thin lines of CTC fluorescence are apparent in the metaphase half spindle; this fluorescence pattern mimics the distribution of the intraspindle membrane system and suggests that it is rich in associated Ca2+. We suggest that the intraspindle membrane system functions in the regulation of cytosolic Ca2+ during meiosis through sequestration of the cation.

Animals↗

The ultrastructure of an intraspindle membrane system in meiosis of spider spermatocytes.

An extensive system of membranes was found in the spindles of spermatocytes of two wolf spider species, Lycosa georgicola and L. rabida. Serial section reconstructions of this membrane system revealed that each meiotic bivalent is encased in a tube of membrane, which encloses both kinetochore microtubule bundles and approaches to within a few microns of the centriolar complex. The membrane tube is open at the polar ends. The membrane composing the tube is doubled and resembles smooth endoplasmic reticulum (ER). No evidence of nuclear pore complexes has been found in the intraspindle membrane system, but typical pores are present on the nuclear envelope of prophase cells. The membrane tubes are fenestrated and microtubules sometimes penetrate these fenestrae. Besides its possible function in the regulation of chromosome movement, the intraspindle membrane system may participate in the nonrandom segregation of the sex chromosomes at meiosis in these spiders.

Anaphase↗

Non-random chromosome segregation in Neocurtilla hexadactyla is controlled by chromosomal spindle fibres: an ultraviolet microbeam analysis.

Single spindle fibres of Neocurtilla spermatocytes were irradiated by means of an ultraviolet microbeam. Irradiations were with monochromatic ultraviolet light. The single sex chromosome (the X1 univalent) reoriented after irradiation of its spindle fibre or of any of the spindle fibres associated with the heteromorphic bivalent (the X2Y bivalent): the X1 moved toward the Y half-spindle, and sometimes rotated as it moved. Irradiations of autosomal spindle fibres did not induce X1 movements, and hence the induction of reorientation is specific to irradiation of the spindle fibres associated with X1 or X2Y. In no case did the X2Y bivalent reorient; hence, the X1 is the active chromosome in ensuring that there is non-random segregation in Neocurtilla spermatocytes. The irradiations sometimes caused the X2Y bivalent to contrast, but the reorientation movements of the X1 were independent of the contraction of the X2Y bivalent. We suggest that the X1 and X2Y chromosomal spindle fibres form a network that is able to send signals to the X1 univalent to cause it to reorient.

Animals↗

Prometaphase forces towards opposite spindle poles are not independent: an on/off control system is identified by ultraviolet microbeam irradiations.

Individual spindle fibres in prometaphase spermatocytes of the cricket, Neocurtilla hexadactyla, were irradiated with an ultraviolet microbeam. The stretched heteromorphic bivalent (X2Y) contracted to about 75% of its pre-irradiation length after irradiation of either of its two oppositely directed spindle fibres (i.e., the X2 or Y spindle fibre). The X2Y bivalent also contracted after irradiation of the connection between the kinetochores of the univalent X1 chromosome and the Y chromosome but it did not contract after irradiation of autosomal spindle fibres or of the spindle fibre of the X1 univalent sex chromosome. The spindles sometimes shrank after irradiation, but contraction of the X2Y bivalent was independent of spindle shrinkage. The data strongly suggest that the oppositely directed forces on a bivalent are not independent. One reason is that the X2Y contractions were asymmetrical: during contraction one kinetochore remained fixed in position while the other kinetochore (facing the opposite pole) moved towards the equator. In 75% of the cases the stationary kinetochore was associated with the irradiated spindle fibre. Thus, we suggest that the irradiation of a spindle fibre produces a state analogous to rigor in the irradiated spindle fibre and, because of effects on the control system, produces relaxation of tension in the oppositely directed non-irradiated spindle fibre, so that the kinetochore associated with the non-irradiated spindle fibre moves towards the equator. These experiments have identified a control system that coordinates force production to opposite poles.

Animals↗

Electron microscopy of complexes of isolated acetylcholine receptor, biotinyl-toxin, and avidin.

The principal curarimimetic toxin of Naja naja siamensis derivatized with biotinyl groups binds specifically both to acetylcholine receptor, isolated from Torpedo californica electric tissue, and to avidin. Isolated complexes of receptor monomer or dimer, biotinyl-toxin, and avidin were negatively stained and examined in the scanning transmission electron microscope. We measured the angle made by the radius of each avidin bound at the periphery of a monomeric unit in dimer to the axis connecting the centers of the monomers, starting at the crosslink between the monomers. We infer from the distribution of these angles that one toxin binding site is located in the range of 45 degrees to 85 degrees and another at about 100 degrees further from the crosslink between the monomers. Because it is known that there are two toxin binding sites per monomer, associated with the two alpha chains, the bound avidins presumably point to portions of the alpha chains, indicating their positions relative to that portion of the delta chain located at the crosslink between monomers in dimer.

Animals↗

Traction force on a kinetochore at metaphase acts as a linear function of kinetochore fiber length.

We are investigating the relation between the force pulling a kinetochore poleward and the length of the corresponding kinetochore fiber. It was recognized by Ostergren in 1950 (Hereditas 36:1-19) that the metaphase position of a chromosome could be achieved by a balance of traction forces were proportional to the distance from kinetochore to pole. For the typical chromosome (i.e., a meiotic bivalent or mitotic chromosome) with a single kinetochore fiber extending to each pole, the resultant force (RF) would equal zero when the chromosome lay at the midpoint between the two poles. For special chromosomes that have unequal numbers of kinetochore fibers extending towards opposite poles. For special chromosomes that have unequal numbers of kinetochore fibers extending towards opposite poles. For special chromosomes that have unequal numbers of kinetochore fibers extending towards opposite poles, Ostergren's proposal suggests that RF = 0 when the chromosome is shifted closer to the pole toward which the greater number of kinetochore fibers are pulling. We have measured the force-length relationship in living spindles by analyzing the metaphase positions of experimentally generated multivalent chromosomes having three or four kinetochore fibers. Multivalent chromosomes of varied configurations were generated by gamma-irradiation of nymphs of the grasshopper melanoplus differentialis, and their behavior was analyzed in living first meiotic spermocytes. The lengths of kinetochore fibers were determined from time-lapse photographs by measuring the kinetochore-to-pole distances for fully congressed chromosomes just before the onset of anaphase. In our analysis, force (F) along a single kinetochore fiber is expressed by: F = kL(exp), where k is a length-independent proportionality constant, L represents the kinetochore fiber length, and exp is an unknown exponent. The RF on a chromosome is then given by: RF = sigmak(i)L(i)(exp), where kinetochore fiber lengths in opposite half- spindles are given opposite sign. If forces on a metaphase chromosome are at equilibrium (RF = 0), then for asymmetrical orientations of multivalents we can measure the individual kinetochore fiber lengths (L(i)) and solve for the exponent that yields a resultant force of zero. The value of the exponent relates how the magnitude of force along a kinetochore fiber varies with its length. For six trivalents and one naturally occurring quadrivalent we calculated an average value of exp = 1.06 +/- 0.18. This result is consistent with Ostergren's hypothesis and indicates that the magnitude of poleward traction force along a kinetochore fiber is directly proportional to the length of the fiber. Our finding suggests that the balance of forces along a kinetochore fiber may be a major factor regulating the extent of kinetochore microtubule assembly.

Animals↗

Nonrandom chromosome segregation in Neocurtilla (Gryllotalpa) hexadactyla: an ultrastructural study.

During meiosis I in males of the mole cricket Neocurtilla (Gryllotalpa) hexadactyla, the univalent X1 chromosome and the heteromorphic X2Y chromosome pair segregate nonrandomly; the X1 and X2 chromosomes move to the same pole in anaphase. By means of ultrastructural analysis of serial sections of cells in several stages of meiosis I, metaphase of meiosis II, and mitosis, we found that the kinetochore region of two of the three nonrandomly segregating chromosomes differ from autosomal kinetochores only during meiosis I. The distinction is most pronounced at metaphase I when massive aggregates of electron-dense substance mark the kinetochores of X1 and Y chromosomes. The lateral position of the kinetochores of X1 and Y chromosomes and the association of these chromosomes with microtubules running toward both poles are also characteristic of meiosis I and further distinguish X1 and Y from the autosomes. Nonrandomly segregating chromosomes are typically positioned within the spindle so that the kinetochoric sides of the X2Y pair and the X1 chromosome are both turned toward the same interpolar spindle axis. This spatial relationship may be a result of a linkage of X1 and Y chromosomes lying in opposite half spindles via a small bundle of microtubules that runs between their unusual kinetochores. Thus, nonrandom segregation in Neocurtilla hexadactyla involves a unique modification at the kinetochores of particular chromosomes, which presumably affects the manner in which these chromosomes are integrated within the spindle.

Anaphase↗

Relationship between biochemical and clinical features in an English Anderson-Fabry family.

The relationship between biochemical parameters and clinical symptoms in angiokeratoma corporis diffusum universale (Anderson-Fabry's disease) has been studied in an extensive English family. The biochemical parameters measured were alpha-galactosidase activity in urine and in single hair roots and the urinary glycosphingolipid excretion per 24 h. The clinical symptoms evaluated included the occurrence of pain, the prevalence of skin lesions, an abnormal ECG, cornea verticillata and other features. Nine male patients and 13 female carriers were studied. No correlation between biochemical parameters and the severity of the clinical symptoms could be found either in the hemizygotes or in the heterozygotes. The urinary alpha-galactosidase activity in all the heterozygotes lay within the normal range. All the obligate heterozygotes (mothers and daughters of hemizygotes) could be detected by analysis of hair roots. Additional heterozygotes were recognized on the basis of clinical symptoms and hair root analysis.

Adolescent↗

On the mechanism of prometaphase congression: chromosome velocity as a function of position on the spindle.

Rates of movement of univalents at prometaphase and of half-bivalents at anaphase in living cricket and grasshopper spermatocytes were determined as a function of the distance from the pole toward which the movement was directed. In the artificially produced univalents of cricket cells, correlation coefficients for rate versus distance form the pole were widely disparate from movement to movement and there was no consistent relationship between velocity and distance from the pole. However, in the naturally occurring univalents of grasshopper cells, there was a significant positive correlation between velocity and distance from the pole. In both cricket and grasshopper cells, there was no consistent correlation between rate of movement and distance from the pole for half-bivalents at anaphase. The prometaphase data from grasshopper cells support the simple hypothesis of Ostergren (1950) that congression results from the application to chromosomes of forces which increase with increasing distance from the pole. Furthermore, these data are consistent with models of force production which suppose that the relationship between force (reflected as velocity) and distance from the pole is a linear one.

Animals↗