Mechanisms of proliferative and obliterative vascular diseases. Insights from the pulmonary and systemic circulations. NHLBI Workshop summary.
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Biomedical subjects
Publications and source records attributed to D Robinson.
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Microscopy is a useful and direct method for measuring the particle size of a suspension because, in addition to the particle size and size distribution, it provides visual detection of the shape and state of aggregation of the particles in the suspension. However, this method suffers from the shortcomings of being tedious and time consuming. In this study, a light-scattering particle size analyzer was used to determine the particle size and size distribution of a flocculated suspension. The sonication of the sample prior to and during measurement was found to be critical in ensuring that data are representative of the size distribution of the primary particles of the suspension. The light-scattering results were further confirmed by data generated using a polarized light microscope equipped with an image analyzer.
Information about a subject's lifestyle, personal past history and family history of disease is obtained from a 70-item questionnaire. This information is then used to compute the subject's risk of dying from certain diseases, relative to the average risk for a person of the same age and sex.
Dietary habits are believed to play an important role in the etiology of adult disease. For this reason, it is necessary to include effective dietary guidance in multiphasic health testing and services (MHTS) programmes for primary disease prevention. We have developed such a programme of simple dietary advice, using a computer system for the MHTS. Examinees' dietary habits are checked using optical character record (OCR) questionnaire forms, and the results are displayed on the screen of a colour display terminal. They are required to prepare a menu of their usual daily dietary intake in terms of quantity and type of food. Thus the data collected relate to the nutritional composition of the examinee's usual diet. Nutritional requirements of the Japanese according to sex, height, and level of physical activity, in accordance with criteria set by the Japanese Ministry of Health and Welfare, are fed into the computer in advance. For each examinee, these criteria and the results of the assessment of the diet are displayed together on the screen in the form of colour graphs for comparison.
The assembly of the photosynthetic apparatus requires the import of numerous cytosolically synthesised proteins and their correct targeting into or across the thylakoid membrane. Biochemical and genetic studies have revealed the operation of several targeting pathways for these proteins, some of which are used for thylakoid lumen proteins whereas others are utilised by membrane proteins. Some pathways can be traced back to the prokaryotic ancestors of chloroplasts but at least one pathway appears to have arisen in response to the transfer of genes from the organelle to the nucleus. In this article we review recent findings in this field that point to the operation of a mechanistically unique protein translocase in both plastids and bacteria, and we discuss emerging data that reconcile the remarkable variety of targeting pathways with the natures of the substrate precursor proteins.
We report the first isotopic study of an animal host-parasite system. Parasitic, intestinal nematodes, Graphidium strigosum and Passalurus ambiguus, were 15N-enriched relative to their host, the European rabbit Oryctolagus cuniculus, while parasitic cestodes, Cittataenia denticulata and Mosgovoyia pectinata, were 15N-depleted, suggesting different trophic relationships. Host embryos were more similar in their delta 13C and delta 15N values to maternal muscle than were any of the parasites. Coprophagy, the direct recycling of food by the rabbit eating its own faeces, did not lead to isotopic differences between stomach contents and faeces, suggesting that the major point for isotopic discrimination in lagomorph nitrogen metabolism is in the animal rather than in the gut. We conclude that bulk delta 13C and delta 15N can reveal valuable new information about host-parasite relationships, and these could be explored further at the biochemical level using compound-specific isotopic analyses.
Documentation of the administrative aspects of clinical practice (fee claims, referrals, visits etc.) is essential and a controlled terminology for the electronic health care record needs to support this requirement. The Read Codes--used in the United Kingdom for over 10 years--include a chapter of administration terms for this purpose. The latest version, the Read Thesaurus, adopts a partially compositional approach to concept representation. We describe an extension of the ENV 1828 surgical procedure scheme developed as a provisional model to represent administrative procedures. Applicable concept fields, semantic links and modifiers are identified and compared. A compositional approach appears to provide a flexible and manageable method of representing administrative procedures, and readily accommodates regional variations.
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Glutamate is required for the transmission of inspiratory drive in respiratory premotor and motor neurons. The glutamate receptors (GluRs) responsible for this essential function have yet to be anatomically characterized. We mapped the GluR subtypes expressed by respiratory premotor and motor neurons by using combined immunohistochemistry and retrograde labeling in adult rats. Phrenic motoneurons and bulbospinal ventral respiratory group (VRG) neurons were retrogradely labeled and immunolabeled with subunit-specific antibodies against the N-methyl-D-aspartate (NMDA) receptor subtype (NMDAR1) and the non-NMDA receptor subtypes, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA; GluR1, GluR2/3, GluR4) and kainate (GluR5-7). Phrenic motoneurons and bulbospinal VRG neurons showed positive immunolabeling for all five GluR subunits. These results support the hypothesis that NMDA and non-NMDA receptor subtypes underlie the excitation of bulbospinal VRG neurons and phrenic motoneurons. Furthermore, immunolabeling for each receptor subtype demonstrated a unique distribution along the neuronal membrane. Immunoreactivity for AMPA receptor subunits was distributed throughout somata and proximal dendrites, NMDAR1 subunit immunolabeling was localized to somata, and GluR5-7 subunit immunolabeling was confined largely to dendrites. The differential distribution of AMPA, kainate, and NMDA receptors on the somal and dendritic surface of respiratory neurons suggests that the location of glutamatergic synapses along the neuronal surface is an important determinant of glutamate-mediated postsynaptic currents. Consequently, different patterns of glutamatergic excitation of respiratory neurons could be achieved by selective activation of different profiles of GluR subtypes on different portions of the neuronal membrane.
It is often difficult to assess accurately the nature of a skeletal lesion. Problems include differentiating a malignant from a benign bone tumor, as well as determining the cause of a pathologic fracture. Such fractures may occur through osteoporotic bone as well as through neoplasm-affected bone. Thus, development of an imaging modality capable of distinguishing between such lesions is of importance. During 1996, we ran a prospective study in which results of Tc-99m-methyl-diphosphate (MDP) bone scans were compared with those of sestamibi (MIBI) bone scans and with subsequent biopsy and clinical course. The results of the bone scans were assessed by 2 independent "blinded" observers, and the ratios of counts in lesions to those in normal tissue (L/N ratios) were calculated. In cases of malignant (7) and benign (8) tumors, intensity of uptake in MDP scans were not predictive of degree of aggressiveness. On the other hand, MIBI bone scans demonstrated significant difference in intensity of uptake between benign and malignant bone tumors (L/N ratios 2.05 vs 2.75). In 5 of 8 benign lesions the L/N ratio was 1. In the others, increased uptake was minimal. In 2 patients changes in uptake in MIBI bone scan following chemotherapy appeared to be related to the degree of tumor necrosis achieved. While the MIBI bone scan cannot replace tissue biopsy as a definitive diagnostic modality in bone neoplasms, it does appear to allow better preoperative assessment and prognosis.
In 1995, Rampton Hospital was designated as the national centre for people with learning disabilities requiring secure care. Since then, the nursing research unit at Rampton Hospital has examined quality of care and patient satisfaction with some of this client group (Fisher 1994, Robinson 1996, Robinson and Reed 1996). This article reports the findings of an exploratory study to measure the quality of life for people with learning disabilities based on a study carried out at the Elwyn Community Learning Disability Unit in the United States.
The genetic factors which predispose individuals to dementia in old age have not been fully defined. Although the apolipoprotein E4 allele accounts for a proportion of the genetic risk for late-onset Alzheimer disease (AD), it is neither necessary nor sufficient to cause this disease. Recent suggestions that other loci are involved in dementia risk have been supported by findings of associations of genotypes at the alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) loci with AD. We investigated these loci in two community-based aged Cambridgeshire populations: the rural Ely population (cohort 1) comprised 60 pairs of demented and nondemented elderly individuals, with a mean age of 84.2 years; and the Cambridge city population (cohort 2) comprised 81 pairs all over age 84, with a mean age of 87.3 years. Since vascular risk factors are likely to impact on dementia risk, we also examined the angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR) genes as candidates. ACE, ACT, PS-1, and MTHFR genotype and allele frequencies were not significantly different in cases and matched controls. These data support the doubts which have been raised about the involvement of the PS-1 and ACT polymorphisms in late-onset dementia.
This article describes how a working group examined ways to overcome difficulties with applying research findings to clinical practice. The group developed a ward-based distance learning package to assist in developing staff skills and ultimately enhance patient health care. The package has implications for all registered nurses in all nursing contexts.
Condensation is the performance of an effective pelvic muscle contraction increases urethral and vaginal pressures and is independent of demographic, clinical, and urodynamic factors. Our objective was to examine the relationship between urethral closure pressure and vaginal pressure during a pelvic muscle contraction in minimally trained women. Our secondary aim was to determine whether demographic, clinical, or urodynamic factors predict pelvic muscle contraction performance. Two hundred two women with urinary incontinence underwent multichannel urodynamic evaluation, including urethral profilometry and measurement of vaginal pressure during pelvic muscle contraction. One hundred forty-four women were diagnosed with genuine stress incontinence, 28 with detrusor instability, and 30 with mixed incontinence. Urethral and vaginal pressures correlated significantly during pelvic muscle contraction (P < or = 0.006). The ability to perform an adequate pelvic muscle contraction was independent of subject age, parity, hormonal or hysterectomy status, clinical severity, urethral support, and urethral profilometry measures (P > or = 0.42).
BACKGROUND: IL-5-producing allergen-specific T cells are thought to play a prominent role in the pathogenesis of allergic inflammation. We hypothesized that T cell allergen-driven IL-5 synthesis is elevated in patients with atopic disease as compared with that in atopic patients free of disease and nonatopic control subjects. OBJECTIVES: The purpose of this study was to compare IL-5 and interferon-gamma (IFN-gamma) secretion and proliferation by peripheral blood T cells from sensitized atopic patients with asthma, rhinitis, and no symptoms and from nonatopic control subjects in response to the allergen Dermatophagoides pteronyssinus (Der p) and the control recall antigen Mycobacterium tuberculosis purified protein derivative (PPD). METHODS: To measure allergen-induced IL-5 production and proliferation, we developed a short-term culture technique that required a single antigenic stimulation of freshly isolated peripheral blood mononuclear cells (PBMC). With this technique, we measured Der p- and PPD-induced IL-5 production and proliferation in PBMC from atopic patients with asthma who were allergic to Der p, atopic patients with rhinitis, atopic patients with no symptoms, and a group of nonatopic normal control subjects. In four experiments, CD4+ or CD8+ T cells were depleted from PBMC to confirm that IL-5 synthesis was T cell dependent. RESULTS: T cell IL-5 production, but not IFN-gamma production, in response to Der p was elevated in atopic patients with asthma and atopic patients with rhinitis compared with findings in atopic patients with no symptoms or nonatopic control subjects. IL-5 production was abrogated by depletion of CD4+, but not CD8+, T cells. In subjects with asthma, allergen-driven IL-5 production correlated with bronchial hyperreactivity. Allergen-induced proliferation was also higher in patients with asthma than in atopic subjects with no symptoms or nonatopic controls. T cell IL-5 and IFN-gamma production and proliferation in response to PPD were similar regardless of atopic status or disease. CONCLUSIONS: Elevated IL-5 production is a characteristic of allergen-specific peripheral blood CD4+ T cells from sensitized patients with atopic disease but not atopy per se.
Multiunit or single unit activity recorded simultaneously from frontal cortex (FC) and locus coeruleus (LC) under ketamine anesthesia revealed that both regions show slow oscillatory activity, together or separately. If, however, both regions are engaged in this oscillatory activity, there is a systematic relationship between their phases with peak LC firing always following FC firing by 200-400 ms. This was confirmed by cross-correlational analyses, which indicated that the two structures temporarily form a resonant system. The FC-LC resonant state is, however, loose enough to remain open to other intrinsic or extrinsic influences, keeping the measured frequencies of oscillations at each site slightly different, as demonstrated by a detailed analysis of the autocorrelograms. An injection of lidocaine at the frontal cortex site, while sharply reducing the prefrontal activity to essentially zero, leads to an increase of the LC activity and to a modification of the shape of the LC autocorrelogram, but does not change appreciably the phase relationship between the activity in the two structures during the diminishing activity in FC.
In these studies, IFN gamma-inducing factor (IGIF), unlike IL-12, did not drive Th1 development in BALB/c or C57BL/6 mice, but like IL-1alpha, potentiated IL-12-driven Th1 development in BALB/c mice. IGIF and IL-12 synergized for IFN gamma production from Th1 cells. Unlike IL-1alpha, IGIF had no effect on Th2 cells. IGIF signaled through IRAK, IL-1 receptor-associated kinase, to induce nuclear translocation of p65/p50 NFkappaB in Th1 cells. IL-1alpha had no effect on proliferation, cytokine production, or NFkappaB activation in Th1 cells but activated NFkappaB and proliferation in Th2 cells. Thus, Th1 and Th2 cells may differ in responsiveness and receptor expression for IL-1 family molecules. IGIF and IL-1alpha may differentially amplify Th1 and Th2 effector responses, respectively.
1. Laboratory studies have shown that cold exposure causes an increase in blood pressure, cholesterol and erythrocyte count. However, whether the mild cold exposures received during everyday life are sufficient to cause such changes is unclear. 2. To test this, outdoor temperatures in central London between 1986 and 1992 were related to both haematological and blood pressure data on 50-69-year-old men attending BUPA health screening examinations in London, and to mortality in South-East England. Since any association with temperature may be an artifact due to common, temperature-independent, annual rhythms in the parameters, these data were also analysed after removal of these circannual components by digital filtering. 3. It was found that short-term falls in temperature produced significant increases in Hb, erythrocyte count, packed cell volume, mean corpuscular Hb concentration, serum albumin, systolic and diastolic blood pressure, and significant decreases in mean corpuscular volume and erythrocyte sedimentation rate. Mean corpuscular Hb, leucocyte count, platelet count and serum cholesterol concentrations were unchanged. Time-series analysis showed that these changes occurred almost immediately in response to a fall in temperature, but persisted for longer intervals of up to 1-2 days. 4. Mortalities from ischaemic heart disease and cerebrovascular disease were also significantly increased by short-term falls in temperature. 5. These finding indicate that in the general population the cold exposures of normal life are sufficient to induce significant and prolonged haemoconcentration and hypertension, which may explain why deaths from arterial disease are more prevalent in the winter.