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Biomedical subjects

B Walker

Publications and source records attributed to B Walker.

At least 217 records · Page 12Linked to original sources

Cytomegalovirus in a macerated second trimester fetus: persistent viral inclusions on light and electron microscopy.

The macerated stillborn fetus represents at least one third of all perinatal deaths. Microscopic examination of these specimens is often unrewarding. We have reported a clinically unsuspected cytomegalovirus infection in a second trimester macerated fetus. Cells suggestive of CMV inclusions were identified by light microscopy, but electron microscopy confirmed the presence of viral infection and proved valuable in making the diagnosis even though necrosis was severe.

Abortion, Spontaneous↗

Novel C-terminal gastrin antagonists. Synthesis and biological activity.

The C-terminal tetrapeptide, Trp-Met-Asp-Phe-NH2, is a full agonist of gastrin, but des-Phe analogues, including Boc-Trp-Met-Asp-NH2, are antagonists. To ascertain the minimum structural requirement for an antagonist, we used conventional solution phase methodology to synthesize analogues with further modifications including removal of the alpha-amino group of Trp, conversion of the indole to a phenyl ring, and methylation of amide bonds. These analogues were tested for their effect on pentagastrin-stimulated acid release in dogs surgically prepared with a gastric fistula. When infused intravenously at a dose of 20 pmol kg-1 h-1, the peptides significantly inhibited acid secretion. The extent of inhibition ranged from 12% to 60%. Thus, tripeptide analogues based on the C-terminal sequence of gastrin act as potent and specific antagonists of gastrin-stimulated acid secretion.

Amino Acid Sequence↗

Visualisation of the gastrin receptor within rat mucosa using a biotinylated gastrin antagonist.

We have previously demonstrated that the peptide Boc-L-Trp-L-Leu-beta-Ala is a potent and specific antagonist of pentagastrin-stimulated acid secretion in both the rat and the dog. Using conventional solution phase methodology, the analogue biotinyl-L-Trp-L-Leu-beta-Ala was prepared in reasonable yield and purity and applied to cryostat sections of rat intestinal and other tissues. The sections were exposed to 5-10 micrograms of peptide and the bound analogue was visualised using streptavidin-fluorescein. The binding of the analogue was demonstrated in sections from fundus, duodenum, ileum, colon, and lung. However, the analogue failed to bind to tissue from the pancreas, heart, kidney, or liver. The binding of the probe was greatly reduced or completely inhibited by preincubation with Boc-L-Trp-L-Leu-beta-Ala, pentagastrin, or gastrin 1-17. The distribution of the cells recognised by the probe was consistent with the distribution of histamine-containing enterochromaffin-like cells. The results of this study may have some bearing on current theories of the mechanism of gastrin-stimulated acid release.

Amino Acid Sequence↗

Prediction of survival by the Clifton Assessment Procedures for the Elderly (CAPE).

A sample of 261 elderly patients, most with a diagnosis of dementia, consecutively admitted to a geriatric psychiatry assessment ward, was assessed using the cognitive assessment scale (CAS) and behaviour rating scale (BRS) of CAPE. Scores of patients alive at four follow-up intervals were compared with those of non-survivors. On CAS, survivors scored significantly better at 18- and 48-month follow-up; and better, but not significantly so, at nine- and 36-month follow-up. On BRS, survivors scored significantly better at all four follow-up intervals. Only at 36-month follow-up did the scales predict survival of individual patients more efficiently than did base rates.

Activities of Daily Living↗

Environmental health policies in the 1990s.

After almost a decade of suspension between progress and retrogression, environmental issues are back at the top of the national agenda. The evidence is visible in many forums of public discussion. But the development and implementation of a new wave of environmental policies will require attention to at least three issues: setting priorities, emphasis on science and technology, and a focus on human resources development.

Environmental Health↗

Tear gas--harassing agent or toxic chemical weapon?

Tear gas has gained widespread acceptance as a means of controlling civilian crowds and subduing barricaded criminals. The most widely used forms of tear gas have been o-chlorobenzylidenemalononitrile and omega-chloroacetophenone. Proponents of their use claim that, if used correctly, the noxious effects of exposure are transient and of no long-term consequences. The use of tear gas in recent situations of civil unrest, however, demonstrates that exposure to the weapon is difficult to control and indiscriminate, and the weapon is often not used correctly. Severe traumatic injury from exploding tear gas bombs as well as lethal toxic injury have been documented. Moreover, available toxicological data are deficient as to the potential of tear gas agents to cause long-term pulmonary, carcinogenic, and reproductive effects. Published and recent unpublished in vitro tests have shown o-chlorobenzylidenemalononitrile to be both clastogenic and mutagenic. Sadly, the nature of its use renders analytic epidemiologic investigation of exposed persons difficult. In 1969, eighty countries voted to include tear gas agents among chemical weapons banned under the Geneva Protocol. There is an ongoing need for investigation into the full toxicological potential of tear gas chemicals and renewed debate on whether their use can be condoned under any circumstances.

Adult↗

Growth-inhibitory and growth-stimulatory effects of epidermal growth factor on human breast cancer cell line, MDA.MB.436: dependence on culture conditions.

Epidermal growth factor (EGF) is growth inhibitory for some cell lines, especially those having over-expressed EGF receptors. We have examined the effects of murine EGF on the growth of the human breast cancer cell line, MDA.MB.436, which has low numbers of EGF receptors. In the presence or absence of serum a 6 day exposure to 0.1 ng/ml EGF causes inhibition of growth if the culture medium is left unchanged during the course of the experiment but the same concentration of EGF causes stimulation above control if the EGF-containing medium is replaced daily. A 1 day exposure to 0.1 ng/ml followed by return to control medium has no effect on subsequent growth. The cells do not synthesize EGF receptor binding activity and added EGF is degraded within 2 days, suggesting that the inhibitory effects of EGF persist in its absence.

Breast Neoplasms↗

Chemotherapy plus RA233 in the treatment of oat cell lung cancer.

One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vincristine, and etoposide (VP-16)] chemotherapy +/- RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.

Actuarial Analysis↗

Physiological adaptation to the environment.

The ability of an animal to cope with new environments arises from its capacity to respond to environmental variables and maintain body equilibrium (homeostasis). Each compensating mechanism depends on, and is a part of, a physiological feedback process. The severity (intensity and duration) of an environmental change relative to the animal's capacity to respond determines the potential disruption to the animal's equilibrium and the resources that must be invested to regain homeostasis. However, an environmental change sufficient to seriously challenge one individual may be insufficient to produce a measurable response in another. The principles behind the responses occurring in animals as a consequence of a change in their physical environment are illustrated in this review by examples drawn from responses of animals to cold stress. Behavioral opportunities sometimes are constrained in farm animals, and internal metabolic responses tend to become more prominent in such situations. Furthermore, as a disturbing factor persists, the immediate defensive responses are replaced by longer-term and adaptive mechanisms that reduce the burden on the animal. As we gain greater understanding of the environment-animal interface and the sensitivity and response of animals to disruption, we will be better able to establish and maintain suitable environments for our farm animals.

Adaptation, Physiological↗

Bioactivity studies on new gastrin analogues.

Gastrin antagonists may be useful in the treatment of peptic ulcer disease and gastrointestinal malignancies. The aim of the present study was to synthesize gastrin analogues and test them for their ability to inhibit gastrin-stimulated acid secretion. Five peptides were synthesized: peptide [2], in which methionine was replaced by leucine, and the COOH-terminal amide was replaced by the thiomethylamide; peptide [3], in which the COOH-terminal phenylalanine was removed, and the aspartic acid thioamidated; peptide [5], in which methionine was replaced by leucine, and the peptide bond between leucine and aspartic acid was replaced by a thioamide; peptide [7], in which the bond between leucine and aspartic acid was replaced by a ketomethylene amino bond; and, finally, peptide [8], in which a beta-bend was induced in the COOH-terminal region by the introduction of a D-phenylalanine in place of glycine. The biologic effect of the peptides was tested in the totally isolated, vascularly perfused rat stomach. The peptides were tested in concentrations of 10(-9), 10(-7), and 10(-5) M for agonist activity and together with gastrin 1-17, 5.2 X 10(-10) M, at a concentration of 10(-5) M for antagonist activity. Peptide [2] had full biologic activity but greatly reduced potency, and peptide [7] had a faint biologic activity. None of the peptides showed any antagonist activity.

Amino Acid Sequence↗

The Future of Public Health: the Institute of Medicine's 1988 report.

A long list of enduring and emerging public health issues have raised questions about the capacity of the public health service system to address these concerns. A two-year Institute of Medicine study revealed a system in disarray. It is inappropriately politicized, and public health responsibilities have become so fragmented that deliberate action is often difficult. The Institute of Medicine's committee emphasized that these issues are complex and affect our society broadly. It called for comprehensive action to bring about necessary changes including a clear delineation of the mission of the public health service system and improvement in technical, political, managerial and programmatic skills of public health practitioners.

Academies and Institutes↗