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Biomedical subjects

M Warnock

Publications and source records attributed to M Warnock.

16 recordsLinked to original sources

Microgranulomatous aspergillosis after shoveling wood chips: report of a fatal outcome in a patient with chronic granulomatous disease.

Chronic granulomatous disease is characterized by recurrent infections that result from an inability of phagocytes to kill organisms effectively. We describe a patient with this disease who developed aspergillus pneumonia after shoveling moldy cedar wood chips. Despite aggressive therapy, the patient's condition deteriorated and he died. At autopsy, the lungs revealed diffuse granulomas, all of the same age, with aspergillus organisms confined to the granulomas. We propose the term "microgranulomatous aspergillosis" for this response, which does not conform to the commonly described aspergillus syndromes. We conclude that susceptible immunosuppressed patients should be advised to avoid occupational situations where high spore concentrations are generated.

Adult

Mechanisms of somatostatin action in RINm5F cells in culture: preliminary evidence for possible altered G protein function.

Octreotide (SMS), a somatostatin analogue, is an established antigrowth peptide, but it does not effectively inhibit the growth of insulinoma cells. In order to study the mechanisms that underlie this apparent lack of an antiproliferative effect on insulinoma tumor cells we established the rat insulinoma cell line, RINm5F, in culture. Cells in culture were tested by incubation in media with and without SMS. To study tritiated [3H]-thymidine incorporation into extracted DNA (TTID), 2 muCi/well of 3H was added for 24 hr, and cells were harvested and assayed for TTID (cpm/microgram DNA). Insulin (IRI) and intracellular cAMP (cAMPi) were measured by RIA. To study the effects of SMS on insulin secretion, conditioned media were sampled after 24 hr. To study the effects of cAMPi, conditioned medium was used to extract cAMPi following incubation with SMS for 15 min. Increasing concentrations of SMS had no significant effect on TTID in the presence of 1% FBS. Trypan blue exclusion tests showed > 90% viable cells throughout all stages of these experiments. There were no significant differences in cell numbers and protein content in the presence of SMS. There was a significant decrease in the secretion of insulin and intracellular cAMP levels in response to 50 nM SMS. However, SMS significantly inhibited TTID in RINm5F cells following a 4-hr pretreatment with pertussis toxin (PT) (23553 +/- 1747 vs 20635 [cpm/microgram DNA] +/- 1983 [SEM], P < 0.01). We conclude that the inhibition of insulin secretion by SMS is associated with an attenuation of cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ethics committees.

Three kinds of ethics committees should be distinguished, the mandatory local hospital or clinic-based committee, the statutory national committee set up to issue licences, or survey issues highlighted by local committees, or in the national press, reporting to Parliament, and publishing annual reports; and the committee established either temporarily or on a permanent basis to examine outstanding and general problems in the morals of medical practice and research, and to advise Ministers as to possible changes in the law. At all levels, such committees will be concerned with moral problems, and can never, therefore, be expected to come up with uniquely 'correct' solutions. Nevertheless they are essential both to reassure the public and to give guidance to the medical profession, both in clinical practice and research. Such committees should, at all levels, have a non-medical chairman, and a high proportion of 'lay' members. They must have regard to common moral sentiments, and to what will be morally acceptable in the country as a whole (though they can never hope for total agreement with their conclusions). Their recommendations, being in the sphere of public rather than private morality will be as far as possible the outcome of consensus, without which legislation is not possible.

Advisory Committees

Sweet's syndrome with lung involvement.

Severe dyspnea and pulmonary infiltrates were associated with recurrent episodes of Sweet's syndrome (acute febrile neutrophilic dermatosis) in a 54-yr-old woman with myelodysplasia. Lung and skin biopsies revealed a sterile infiltration of the interstitial tissues by mature neutrophils. Corticosteroid therapy resulted in rapid clinical improvement; however, recurrent episodes were increasingly resistant to therapy, and she ultimately died from respiratory failure. Sweet's syndrome involving the lung is rare, with only two previously reported cases documented by lung biopsy. Prompt recognition of Sweet's syndrome with lung involvement is important because of the potential for severe respiratory compromise.

Female

Use of the polymerase chain reaction in the diagnosis of unsuspected herpes simplex viral pneumonia: report of a case.

A 30-year-old apparently immunocompetent woman presented with acute respiratory failure (acute respiratory distress syndrome). No etiologic agent was found, and she died 2 weeks later despite antibiotic therapy. Postmortem examination of the lungs showed diffuse organizing alveolar damage with superimposed focal necrotizing peribronchiolar pneumonia. Cultures obtained from lung tissue were negative for virus, fungi, and bacteria. Histopathologic and electron microscopic studies showed that the necrotizing changes were consistent with herpesvirus infection. With the use of a new diagnostic tool, the polymerase chain reaction, a specific diagnosis of herpes simplex virus pneumonia was made, and other viral agents were excluded. The polymerase chain reaction is a sensitive, specific, and rapid technique that may greatly facilitate establishing an infectious etiology in cases of pneumonia.

Adult

Acquisition of peroxidase activity by rat alveolar macrophages during pulmonary inflammation.

The authors investigated the ability of rat alveolar macrophages to acquire peroxidase activity in the course of pulmonary inflammation. Granulomatous pulmonary inflammation was induced in bacille Calmette-Guérin (BCG)-immunized rats by intravenous injection of BCG in mineral oil. In contrast to normal alveolar macrophages, which are peroxidase-negative, alveolar macrophages lavaged from the BCG-treated rats showed significant peroxidase activity in large cytoplasmic inclusions compatible with internalized exogenous material. Alveolar macrophage uptake of intact peroxidase-positive neutrophils was also observed. Maximal numbers of peroxidase-positive alveolar macrophages were observed after the initial influx of neutrophils into the lungs, and peroxidase activity could be demonstrated in cell-free lavage fluid during the acute phase of lung injury. Normal alveolar macrophages acquired peroxidase activity after incubation with peritoneal exudate neutrophils, with purified soluble human myeloperoxidase, and with opsonized erythrocytes. It is concluded that alveolar macrophages acquire peroxidase activity from multiple sources during pulmonary inflammation. Internalization of peroxidase by the alveolar macrophage may serve to clear a potentially toxic enzyme(s) from the alveolar space and contribute to the resolution of pulmonary inflammation.

Animals

Nucleotide sequences of a feline leukemia virus subgroup A envelope gene and long terminal repeat and evidence for the recombinational origin of subgroup B viruses.

Molecular clones of the subgroup A feline leukemia virus FeLV-A/Glasgow-1 have been obtained. Nucleotide sequence analysis of the 3' end of the proviral genome and comparison with the published sequence of FeLV-B/Gardner-Arnstein showed that the most extensive differences are located within the 5' domain of the env gene. Within this domain, several divergent regions of env are separated by more conserved segments. The 3' end of env is highly conserved, with only a single amino acid coding difference in p15env. The proviral long terminal repeats are also highly conserved, differing by only eight base substitutions and one base insertion. Specific probes constructed from the FeLV-A or FeLV-B env genes were used to compare the env genes of various exogenous FeLV isolates and the endogenous FeLV-related proviruses of normal cat DNA. An FeLV-A-derived env probe showed no hybridization to normal cat DNA but detected all FeLV-A and FeLV-C isolates tested. In contrast, an FeLV-B env probe detected independent FeLV-B isolates and a family of endogenous FeLV-related proviruses. Our observations provide strong evidence to support the hypothesis that FeLV-B viruses have arisen by recombination between FeLV-A and endogenous proviral elements in cat DNA.

Antigens, Viral

The Warnock report.

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Advisory Committees

Moral thinking and government policy: the Warnock Committee on Human Embryology.

A parliamentary committee of inquiry was convened in response to growing concern--among the general public and the scientific community--about new techniques in human fertilization and research in embryology. The committee had to enter that jurisprudential minefield, the theoretical relation between morality and the law. When issues arise in which there is no historical tradition, the voice of morality may be genuinely confused and uncertain. But the law, unlike moral opinion, cannot be contradictory; it must be definite, unambiguous, and universally applicable.

Advisory Committees

Schools for all.

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Child