Financial and local action to help the unemployed.
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Biomedical subjects
Publications and source records attributed to R Smith.
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Twelve patients with Paget's disease of bone were treated with high doses of disodium etidronate for one month and compared with patients given treatments for longer periods. The effects of treatment for one month with etidronate 20 mg/kg daily were indistinguishable from six months' continuous treatment with the same dose but significantly better than treatment with 5 mg/kg daily in suppressing biochemical indices of disease activity. Treatment for one month was associated with transient osteomalacia but sustained suppression of bone resorption. Short term treatments with high doses of disodium etidronate may maximise suppression of disease activity but decrease exposure to unwanted effects.
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Ribavirin, a broad spectrum, non-interferon-inducing virustatic chemotherapeutic agent, demonstrates activity against a wide range of RNA and DNA viruses, including the retrovirus known to cause the acquired immune deficiency syndrome. The drug's proposed mechanism of action, as well as pharmacokinetics are discussed, and preclinical toxicity, safety and clinical efficacy studies are presented. To date, the best success has occurred in the use of ribavirin to treat respiratory syncytial virus infection in infants and young children and to treat influenza A and B virus infections in young adults. Viral infections, particularly viral pneumonia, are often life-threatening in infants with severe combined immunodeficiency disease (SCID), and ribavirin aerosol has been used successfully to treat respiratory syncytial virus and parainfluenza virus infection of immunodeficient children. Special note is taken of ribavirin's clinical benefit in treating severe and life-threatening infections caused by the Lassa fever virus and the significant improvement over either the use of immune plasma or supportive therapy alone. Indeed, ribavirin thus emerges as the first antiviral drug that is able to reduce mortality in a highly lethal systemic disease by more than 90%. Additional studies demonstrate the drug's efficacy in acute viral hepatitis, herpesvirus infections, and measles. Controlled clinical trials are underway to test the drug in patients infected with the AIDS virus.
Spleen cells (SC) from tumor-bearing mice and mice immunized with porcine myelin basic protein (MBP) reacted in vitro in E-rosette augmentation assays with MBP and certain of its constituent peptides. Peptides 1-115, 43-169, 64-83, 113-121, and 153-161 reacted significantly with both types of SC, while peptide 1-19 reacted only with SC from MBP-immunized mice. The phenomenon of specific inhibition of peptide reactivity by a moderate excess of a related protein was used to identify peptides as accessible epitopes of that protein. Peptide 113-121 was specifically inhibited by excess MBP when reacted with both types of SC, whereas peptide 64-83 was inhibited by excess MBP only when reacted with SC from MBP-immunized mice. These reactions suggest that the immunizing antigen in tumor-bearing mice is related to MBP but differs in epitopes associated with peptides 1-19 and 64-83.
A sample of chronically disabled arthritic patients was studied in 1981, and again in 1983, using a questionnaire which included attitudinal and mood items. The majority of patients had high pain and disability, and this did not significantly change between 1981 and 1983. The questionnaire was able to significantly discriminate between subjective disability and pain groups. This discrimination was more accurate than that made by orthopaedic surgeons using physical ratings alone, and possible 'good coping' and 'bad coping' profiles emerged.
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In osteogenesis imperfecta the bones are brittle but the teeth, whose dentine contains the same genetic collagen as bone (type I), may be clinically normal. To investigate this paradox we have measured the amino acid composition of insoluble dentine collagen from 16 deciduous and 18 permanent teeth in control subjects and in 59 patients with different forms of osteogenesis imperfecta. In 55 of the patient samples significant differences from normal were found, especially in the number of lysine residues, and in the relative amounts of hydroxylysine to lysine. These results demonstrate the high frequency of biochemical abnormalities in osteogenesis imperfecta. They also suggest that classifications of this disorder based on the presence or absence of clinical dentiogenesis imperfecta are likely to be unsound.
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Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions.
HLA-A, B, C, DR antigen frequencies and Properdin factor B (Bf) allotypes were studied in a group of 44 patients with rapidly progressive periodontitis. HLA-A9 (A24) was the only antigen with a frequency statistically significantly different from the control population. An increased frequency of HLA-A9 was previously reported in periodontal diseases. Our results in a well characterised group of patients adds to the evidence that HLA-A9 plays a role in the susceptibility to severe periodontitis.
It has been claimed that the visual component of audiovisual media dominates young children's cognitive processing. This experiment examines the effects of input modality while controlling the complexity of the visual and auditory content and while varying the comprehension task (recall vs. reconstruction). 4- and 7-year-olds were presented brief stories through either audio or audiovisual media. The audio version consisted of narrated character actions and character utterances. The narrated actions were matched to the utterances on the basis of length and propositional complexity. The audiovisual version depicted the actions visually by means of stop animation instead of by auditory narrative statements. The character utterances were the same in both versions. Audiovisual input produced superior performance on explicit information in the 4-year-olds and produced more inferences at both ages. Because performance on utterances was superior in the audiovisual condition as compared to the audio condition, there was no evidence that visual input inhibits processing of auditory information. Actions were more likely to be produced by the younger children than utterances, regardless of input medium, indicating that prior findings of visual dominance may have been due to the salience of narrative action. Reconstruction, as compared to recall, produced superior depiction of actions at both ages as well as more constrained relevant inferences and narrative conventions.
A basic protein has been purified from the CNS myelin of the gummy shark (Mustelus antarticus). Electroblotting was used to examine the capacity of rabbit antisera raised against this electrophoretically pure protein to recognize myelin basic protein from higher vertebrates. The antisera bound to two shark proteins including the original polypeptide antigen and to chicken, bovine, and human myelin basic proteins. Thus, the shark protein appeared to possess antigenic determinants that have been retained through evolutionary divergence of these proteins. Whereas bovine basic protein caused experimental allergic encephalomyelitis in guinea pigs, animals that received injections of the shark protein showed neither clinical nor histological signs of this disease. However, tests for delayed-type hypersensitivity and for Arthus reaction following injection with the shark protein revealed a T-cell-mediated response to this antigen and substantial cross-reactivity with higher vertebrate basic proteins. Analysis of the amino acid composition of the shark protein, and comparison of its tryptic peptide map with that of the bovine protein, revealed substantial changes in the amino acid sequence. Although the shark protein has some antigenic determinants in common with the proteins from higher vertebrates, it appears that much of the structure differs.
In the course of analyzing sites of proviral integration in tumors induced by mouse mammary tumor virus (MMTV), we have isolated recombinant DNA clones corresponding to the 5' and 3' ends of four endogenous MMTV proviruses present in BALB/c and BR6 mice. This has permitted the structural characterization of each locus by detailed restriction mapping and the preparation of DNA probes specific for the cellular sequences flanking each provirus. These probes have been used to trace the segregation patterns of the proviruses, designated Mtv-8, Mtv-9, Mtv-17, and Mtv-21, in a panel of inbred strains of laboratory mice and to map Mtv-17 and Mtv-21 to mouse chromosomes 4 and 8, respectively. The unambiguous resolution of these four proviruses on Southern blots has greatly facilitated the analysis of other endogenous MMTV proviruses in these inbred mice.