Biomedical subjects
Publications and source records attributed to R Grubb.
Thirty-four mothers to infants seriously infected with group B streptococci (GBS) were investigated for G1m (1) and G3m(5) allotype markers. The frequency of Gm (1, -5) was 14.7%, of Gm(1,5) 20.6% and Gm (-1, 5) 64.7%. There was a marked deficit Gm (1) individuals and the distribution significantly differed from that in the normal Swedish populations.
An IgG Fc-binding protein was isolated from alkaline extracts of group A streptococci type 15 by ion-exchange chromatography and immunosorption on an IgG column. Ample use of protease inhibitors was necessary to achieve successful isolation. 600 micrograms protein was obtained from 60 g bacteria (wet weight). The protein appeared homogeneous on agarose gel and sodium dodecyl sulfate polyacrylamide gel electrophoresis and had an apparent molecular weight of 29,500. It contained appreciable amounts of the amino acids glutamic acid, alanine, leucine, aspartic acid and lysine, but little or no tyrosine, phenylalanine, proline, glucosamine or galactosamine. It precipitated human monoclonal IgG of all four sub-classes in agarose gels as well as polyclonal IgG, IgG Fc and normal human serum. It did not precipitate IgG Fab, IgA, IgM, IgD or free kappa or lambda chains.
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6-Nor-9,10-dihydrolysergic acid methyl ester (IV) was prepared by demethylation of 9,10-dihydrolysergic acid methyl ester (II) with 2,2,2-trichloroethyl chloroformate, followed by reduction of the intermediate carbamate (III) with zinc in acetic acid. The 6-ethyl-V and 6-n-propyl-VI derivatives were prepared by alkylation of IV with the appropriate halide. All of the ergoline derivatives were evaluated for stereotyped behavior in rats, with 6-nor-6-ethyl-9,10-dihydrolysergic acid methyl ester (V) being active but much less potent than apomorphine. Compound VI was evaluated for its effect on blood pressure; at a dose of 30 mg/kg ip, it significantly lowered, diastolic pressure in normotensive rats.
We have earlier reported on a group A streptococcal strain, type M12, which upon serial mouse passage acquired IgG Fc-receptor activity but lost the M-antigen. The passaged strain, 12P, was highly virulent for mice and grew well in normal human blood. The present study particularly concerns the opsonic effect on 12P of rabbit anti-M3, anti-M12 and anti-12P sera, as well as the corresponding IgG F(ab')2. Indirect bactericidal tests showed that the homologous anti-12P seum and IgG F(ab')2 were opsonic. The anti-M3 and anti-M12 had no effect on 12P; surprisingly, however, IgG F(ab')2 isolated from these sera displayed a clearcut opsonic activity. Data are presented which indicate that these "paradoxical" results can be explained by the binding of IgG F(ab')2 with anti-IgG specificity to human IgG, linked to the streptococcal surface through Fc-receptors. Only anti-12P serum, or IgG F(ab')2, were protective for mice on challenge with strain 12P.
Eighty-eight T-type 12 group A streptococcal strains were randomly selected from routine specimens in two epidemiologically unrelated districts. All of 26 M-type 12 strains lacked IgA and IgG Fc-receptors, whereas all 32 M-type 22 strains had IgG Fc-receptors and 20 of them also receptors for IgA Fc. The remaining strains were not further M-typed but 18 of these 30 strains exhibited receptors for IgG and 13 for IgA.
A type 12 group A strain (1800) was passaged serially through mice 25 times. The ability to servive in normal human blood dropped from a growth index of 52 after the first passage to 1 after four passages. After 14 passages the growth index increased again and stabilized above 30. The virulence for mice increased from a LD100 of 10(8) colony forming units (CFU) to 10-100 CFU after 7 passages and then remained constant. The Mqw antigen disappeared after 4 passages as tested by immunodiffusion, electroimmunoassay and indirect bactericidal tests. Three antisera, raised in rabbits against strains originally belonging to types M3, M12 and M46 but devoid of type antigens after mouse passages showed high bactericidal indices against the 1800 strain after 14 or more passages on mice. Anti-type M1 serum was also found bactericidal for the passaged strains. The IgG Fc-receptor activity of the strain isolated after each mouse passage was tested in hemagglutination experiments with human red blood cells coated with "incomplete" anti-Rh and hot hydrochloric acid extracts of the strains. The capacity to agglutinate "Ripley"-coated cells increased gradually during the first 12 passages and subsequently the titres of the extracts stabilized between 1:160 and 1:320. The HUN coat, useful for detection of the G3m (5) maraker gave titraes increasing with the number of passages while the titres for IgG1 coats kept at 1:4 or below. On background of these results, the possible role of the IgG Fc-receptor as a virulence factor is discussed.
Lancefield extracts of 19 types of group A streptococci as well as one group C and one group G strain were examined for agglutination of human red cells coated with various anti-Rh antibodies. Fourteen extracts agglutinated one or more of the coated cell samples, while five did not. The agglutination was inhibited by Fc but not by Fab fragments of human IgG. After mouse passages, three of the non-agglutinating strains acquired agglutinating capacity. At least three different reactivities were distinguished by the action of the extracts on IgG1 and IgG3 coated cells, respectively. Two of the streptococcal extracts, agglutinating the same anti-Rh coated cells, could be further differentiated in hemagglutination inhibition (HAI) experiments using purified IgG3 myeloma proteins. Five selected agglutinating systems were inhibited by purified myeloma proteins of the IgG1, IgG2, and IgG4 subclasses. IgG3 proteins inhibited only two of the five HAI systems.
After electrophoresis of an alkaline extract of type 15 group A streptococci, three main precipitation lines were obtained in diffusion experiments against commercial human polyclonal IgG (lines 1, 2 and 3). Nineteen of 23 sera (83%) from apparently healthy human individuals gave line 3, while 6 of them (26%) gave line 1. The sera giving line 1 did also give line 3. Line 2 was obtained with 2 sera only, also giving lines 1 and 3. Line 3 was caused by a streptococcal Fc-receptor for human IgG, since the line could be displaced by addition of Fc-fragments, but not Fab-fragments of pooled human IgG. Line 1 was shown to be different from line 3, since (1) line 1 was suppressed in contrast to line 3 on absorption of a human serum or commercial polyclonal human IgG with S. aureus; and (2), line 1 was suppressed by Fab-fragments but not Fc-fragments of polyclonal human IgG. Line 2 could be inhibited by addition of peptidoglycan to commercial polyclonal human IgG or a human serum investigated. Another line, 4, obtained in diffusion experiments involving electrophoretically separated alkaline extract of type 15 group A streptococci was type-specific as shown by rabbit antisera to streptococci type M1, M8, M15, and T44, and disappeared on trypsinization of the extract. The component responsible for line 4 in the streptococcal extract, judged to be type-specific M protein, had a mobility different from the component responsible for line 3 in electrophoresis.
Lancefield extract of streptococci group A type 15 precipitates certain human sera and agglutinates red cells coated with some IgG anti-Rh antibodies. The frequency of precipitation varies between populations. The serum component in the precipitate is IgG. The results indicate that an iso-allotypic marker is detected by the extract.
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The relationship of the brain angiographic mode circulation time (AVCT) to the mean transit time of the vascular indicator C15O-labeled hemoglobin (tc15o) and the regional cerebral blood flow (rCBF) as measured by the clearance of the diffusible tracer H2-15O was examined in 38 patients with selected cerebral diseases. The results demonstrate a predictable relationship does exist between the rCBF and tc15o. This relationship is linear when plotted as tc15o vs. 1/CBF. Further, tc150 can be estimated with sufficient accuracy from the AVCT to permit at least a qualitative assessment of rCBF from the cerebral angiogram.
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