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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 415 records · Page 23Linked to original sources

Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197.

Haemophilus influenzae type b (Hib) capsular polysaccharide (PRP) was selectively hydrolyzed to reducing oligosaccharides, and the fraction containing 3-10 ribosylribitolphosphate repeating units (VS) was conjugated by reductive amination to diphtheria toxin (DTx), its nontoxic derivative CRM197 (Dcr), or diphtheria toxoid (DTd). Conjugate DTx-VS retained approximately 1% of native toxicity, which was eliminated by treatment with formalin. Immunization of rabbits with the conjugates elicited antibody (Ab) to PRP and to DTx but not to a model for the linkage determinant. Human adults given single subcutaneous injections had rises in serum Ab to PRP and in bactericidal activity in vitro; the Ab protected infant rats challenged with Hib. Adults had rises also in Ab to DTd, and these Ab protected rabbits against DTx. A series of two injections of the conjugates Dcr-VS and DTd-VS was tested in infants beginning at 19-23 mo of age. Rises in anti-PRP Ab after the primary resembled the rises after PRP vaccine. In contrast to PRP, the conjugates elicited large rises after the secondary vaccinations and a substantial IgG component. Development of bactericidal activity paralleled the rises in anti-PRP Ab. Secondary rises after Dcr-VS were higher than after DTd-VS. In infants 12-16 mo of age, Dcr-VS (but not DTd-VS) elicited strong primary and secondary Ab responses that included IgG and bactericidal activity. Both conjugates produced consistent rises in Ab to DTd.

Adult↗

Isoelectric focusing of human antibody to the Haemophilus influenzae b capsular polysaccharide: restricted and identical spectrotypes in adults.

Serum antibody to the capsular polysaccharide of Haemophilus influenzae b of human adults was analyzed by isoelectric focusing. Restricted antibody spectrotype patterns were commonly observed with as few as one spectrotype in some subjects after immunization with the isolated capsular polysaccharide. Some patterns were as restricted as human hybridoma antibody. There was no correlation of antibody titer and heterogeneity of patterns. The dominant spectrotype persisted unchanged for over 2 yr after immunization, and the pattern detected in preimmunization serum samples persisted unchanged after immunization. Indistinguishable patterns were commonly observed in genetically unrelated adults. Adults immunized with conjugate vaccines, which were composed of oligosaccharides prepared from the capsular polysaccharide that were covalently linked to protein carriers, also produced restricted serum antibody spectrotype patterns. Immunization with the cross-reactive polysaccharide of E. coli K100 induced a spectrotype pattern that was restricted but different from that induced by the H. influenzae b capsular polysaccharide.

Adult↗

Photoaffinity labeling of an interferon-gamma receptor on the surface of cultured fibroblasts.

Highly purified native and recombinant 125I-interferon-gamma was acylated with the photoreactive cross-linking reagent, N-succinimidyl-6(4'-azido-2'-nitrophenylamino) hexanoate. Derivatized interferon covalently labeled a cell surface component with an aggregate Mr = 230,000 +/- 7,000 (n = 7). Photoaffinity labeling was judged to be specific for the IFN-gamma receptor as it did not occur in the absence of light or in the presence of excess unlabeled interferon-gamma.

Affinity Labels↗

Antibodies to chromosome 21 coded cell surface components block binding of human alpha interferon but not gamma interferon to human cells.

Antisera raised against a human X mouse hybrid cell line containing human chromosome 21 as its only human chromosome, block induction of an antiviral state by human alpha interferon (IFN-alpha), block induction of (2'-5')oligoisoadenylate synthetase [2'-5')A synthetase), and block binding of 125I-labeled and 35S-labeled recombinant, human IFN-alpha A, but not 125I-labeled IFN-gamma, to cell surface receptors. The data presented clearly demonstrate that the cell surface receptors for IFN-alpha and IFN-gamma are different, and provide independent evidence of the role of a chromosome 21 coded cell surface molecule in the pathway to the generation of the antiviral state.

2',5'-Oligoadenylate Synthetase↗

A selection for myosin heavy chain mutants in the nematode Caenorhabditis elegans.

The unc-54 gene of Caenorhabditis elegans encodes an abundant myosin heavy chain protein expressed in body-wall muscle cells. We have designed genetic techniques that select directly for unc-54 mutants. This selection is based upon properties of the unc-54 dominant allele e1152. Mutations that eliminate dominance of e1152 are null alleles of unc-54. Deletions have been identified by their genetic properties. We have defined mutationally a number of essential genes near unc-54, and we have described the genetic fine structure of this region of linkage group I. As much as 27% of the unc-54 mutations induced by the bifunctional alkylating agent 1,2,7,8-diepoxyoctane are multisite deletions. Extrachromosomal free duplications that include unc-54 are also described.

Alleles↗

Combination chemotherapy with BCNU, vincristine, mitomycin-C and prednisone in refractory breast carcinoma. A pilot study.

21 patients with metastatic breast cancer, refractory to conventional agents, were treated with a combination of BCNU, vincristine, mitomycin-C and prednisone given every 4 weeks. Only three of the nineteen (15.8%) evaluable patients were observed to have a partial remission, whereas four experienced stabilization of tumor. The sites which responded included skin lesions in two patients and a pleural effusion in 1 patient. This combination resulted in moderate to severe thrombocytopenia in five patients, but was otherwise well tolerated. This pilot study therefore suggests that these four agents in the schedule and doses given do not appear to be superior to any of these agents used singly for advanced, refractory breast cancer.

Adenocarcinoma↗

Failure of mexiletine to relieve severe pruritus.

Mexiletine, an antiarrhythmic drug with pharmacological properties similar to lidocaine, was tested for antipruritic effect in 4 patients with severe pruritus. Although the plasma levels were within the therapeutic range for antiarrhythmic effects, a consistent relief of pruritus could not be found.

Adult↗

Pharmacokinetics in baclofen overdose.

The pharmacokinetics of baclofen analyzed by gas chromatography mass spectrometry in a massive intoxication case (baclofen 1230 mg orally) is presented. In contrast to earlier reports, no increase in the plasma half-life of elimination of baclofen could be observed (t1/2 = 4.58 hours). On the contrary, we found an increased plasma clearance (Clpl = 0.368 l/kg) in this highly intoxicated patient compared to the kinetics usually found in healthy subjects.

Absorption↗

Alcohol consumption of undergraduates at Oxford University.

At the end of the fourth week of the spring term 1982, 734 female and 754 male undergraduates at Oxford University were sent a questionnaire inquiring about their alcohol consumption. Of the 561 women and 522 men who replied, 80% and 85% respectively had drunk alcohol during the previous four days. The mean consumption over the four days was 8 units (equivalent to four pints of beer) for the women and 15 units (equivalent to eight pints of beer) for the men. Two-fifths of the alcohol consumed by women was in the form of wine and three-fifths consumed by men was in the form of beer. Sixteen per cent of female drinkers and 28% of male drinkers did try to limit or cut down their drinking although only four women and seven men consulted a doctor or a counsellor about their alcohol consumption. Student health services should be aware that alcohol may play a part in health or personal problems. Undergraduates might appreciate health education literature on alcohol.

Adult↗