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Biomedical subjects

K L Knight

Publications and source records attributed to K L Knight.

At least 145 records · Page 8Linked to original sources
PubMed1982

Rabbit heavy chain haplotypes--allotypic determinants expressed by VH-CH recombinants.

This report summarizes our current understanding of the heavy chain haplotypes found in our laboratories' rabbits. Independently derived data from several laboratories have been synthesizes into a consistent picture of the linked inheritance of allotypic markers found on the different heavy chain classes and subclasses of rabbit immunoglobulins in pedigreed rabbits, including the families of three apparent VH-CH recombinants. In one recombinant, the entire group of CH markers (C mu, C gamma, and C alpha) recombined with the set of VH. Although in the other two recombinants all CH markers may also have recombined as a group, in one of these only IgG and IgA CH genes were informative; in the other recombinant, only the IgG allotypes were informative. Some allotypic determinants found on IgM molecules ("conformational") appear only when a specific variable region allotype (VHa) is combined with a specific mu constant region allotype (C mu). New combinations of VHa and C mu allotypes were generated in two of the genetic recombinants and led to new "conformational" determinants. The gains and losses observed lend support to the hypothesis that the determinants result from conformations generated by the combination of allotype-specific VH and C mu protein sequences. Conceivably, DNA events that join VH to diversity (D)- and joining (J)-coding sequences or mRNA processing events that splice J to C mu could be involved in generating the sequences that form allotype-specific determinants.

Animals↗
PubMed1982

Heavy chain genes of rabbit IgG: isolation of a cDNA encoding gamma heavy chain and identification of two genomic C gamma genes.

A cDNA library was constructed by using rabbit spleen poly(A)+RNA as template, and from this library was isolated a cDNA clone, p2a2, that encodes 179 amino acids of the heavy chain of rabbit IgG. The nucleotide sequence of p2a2 showed that it encodes the COOH-terminal eight amino acids of the CH1 domain, the hinge region, the CH2 domain, and the NH2-terminal half of the CH3 domain of C gamma. Southern blot hybridization analysis of rabbit sperm DNA showed that two EcoRI fragments hybridized strongly with the C gamma cDNA. The p2a2 cDNA was used as a probe to isolate recombinant Charon 4A phage clones containing C gamma sequences from a genomic library of rabbit liver DNA. Two distinct DNA segments were identified by restriction mapping and hybridization analysis, suggesting that the haploid rabbit genome may contain two different C gamma genes.

Amino Acid Sequence↗
PubMed1982

Receptors for IgA on rabbit lymphocytes. II. Characterization of their binding parameters for IgA.

The specificity of rabbit receptors for IgA (RFc alpha) was investigated on lymphocytes isolated from the Peyer's patches and spleen. Specifically was determined by the inhibition of IgA rosette formation with intact and proteolytic fragments of rabbit and human secretory IgA (SIgA), human myeloma proteins, and secretory component. RFc alpha bound human SIgA as efficiently as rabbit SIgA. Of the human IgA tested, RFc alpha preferentially bound to the IgA2 subclass and most avidity to a multimeric IgA molecule. In addition., the site of the RFc alpha-IgA interactions was localized to the C alpha 2 domain in the Fc portion of IgA. RFc alpha on spleen lymphocytes showed the same pattern of binding specificity toward the human IgA subclasses as the RFc alpha on lymphocytes from Peyer's patches. However, differences between the spleen and Peyer's patches were observed in the interaction of RFc alpha and the rabbit IgA subclasses. RFc alpha on lymphocytes from the Peyer's patches bound the rabbit IgA-g subclass more efficiently than the rabbit IgA-f subclass, whereas the converse was true for the spleen RFc alpha. Human secretory component inhibited IgA but not IgG or IgM rosette formation as a result of its interaction with lymphocytes. These studies suggest: 1) that there may be two types of RFc alpha expressed by lymphocytes in certain tissues, and 2) that there are two closely associated receptors on the lymphocyte--one specific for secretory component and the other for structures within the C alpha 2 domain of IgA.

Animals↗
PubMed1981

Genetic control of the expression of allelic Ig genes at the VH a locus in a1/a2 heterozygous rabbits.

Heterozygous rabbits representing 9 of 15 possible a1 and a2 heavy chain haplotype gene combinations among rabbits in the University of Illinois colony were analyzed for ratios of a1 to a2 in serum immunoglobulin (Ig). The Ig from rabbits of the a1x-y-n81f73g74de12,15 heavy chain haplotype in combination with any of three a2-associated heavy chain haplotypes have higher ratios of a1 to a2 than Ig from rabbits in which a1 is encoded by 4 other heavy haplotypes. For example, the mean a1:a2 ratio for adult a1x-y-n81f73g74de12,15/a2x32y33,- n82,f71g75de12,15 rabbits was 12:1 compared to 5:1 for a1x-y33,30n83,f71g75de12,15/a2x32y33,- n82,f71g75de12,15 heterozygous rabbits. Family studies indicated that the a1:a2 ratio was under the control of the heavy chain chromosomal region or a locus closely linked to it. Whether the regulation is due to varying numbers of VH genes and/or J gene segments, a separate regulator gene, or more efficient joining of certain gene segments, has yet to be determined.

Alleles↗
PubMed1981

Functional studies of rabbit T lymphocytes.

Rabbit spleen and mesenteric lymph node cells were treated with a monoclonal anti-rabbit T-lymphocyte antibody (MAb) and complement and the effect of the treatment on various lymphocyte functions was determined. Lysis of spleen and mesenteric lymph node cells reactive with this MAb, 9AE10, essentially eliminated their proliferative responsiveness to allogeneic lymphocytes in the mixed lymphocyte reaction and to the T-cell mitogens, concanavalin A and phytohaemagglutinin; responsiveness to the B-cell mitogen, anti-immunoglobulin (Ig) was not decreased by lysis of 9AE10+ cells. In addition, the 9AE10+ cells were found to be necessary for the secondary in vitro antibody response to the T-dependent antigen sheep red blood cells (SRBC), as removal of 9AE10+ cells blocked the generation of plaque forming cells (PFC) in culture. The PFC's themselves were not sensitive to lysis by 9AE10 MAb and complement Thus, the 9AE10 MAb appears to recognize cells which have functions characteristic of T lymphocytes and this monoclonal antibody will be useful in further studies of the rabbit cellular immune system.

Animals↗
PubMed1980

Comparison of blood flow in the ankle of uninjured subjects during therapeutic applications of heat, cold, and exercise.

Based on clinical evidence, cryokinetics (alternating cold and exercise) is replacing heat modalities as the preferred therapy for rehabilitation of traumatic musculoskeletal injuries in athletes. Theories have been advanced to explain the clinical successes of cryokinetics, but little scientific data have been collected. Strain gauge plethysmography was used to measure blood flow to the ankle of 12 uninjured male subjects. A repeated measures design was utilized with each subject being tested under six experimental conditions: 1) heat packs, 2) cold packs, 3) control, 4) heat-exercise, 5) cold-exercise, 6) control-exercise. Exercise consisted of 5 three-minute bouts (3.5 mph) interspersed with heat, cold, or control throughout a 45-minute period. Non-exercise, heat and cold were administered for 25 minutes each, followed by 20 minutes without treatment. Instantaneous blood flow was measured regularly during non-exercise periods, estimated during exercise, and total flow was computed by integrating over the 45 minute treatment-post treatment period. Total flow (ml flow/100 ml tissue/min) was greater/p. less than .0002) during cold-exercise than during heat treatments. Contrary to some theories, there was neither cold-induced vasodilatation during, nor a reflex vasodilatation following, the 25-minute cold application. These data suggest that during cryokinetics, exercise causes the increased blood flow, and that cold applications function only to allow active motion in a painful joint.

Adult↗
PubMed1980

Free sulfhydryl groups of rabbit secretory IgA.

The reaction of sIgA with 5,5'dithiobis (2-nitrobenzoic acid) or with 14C-iodoacetamide revealed an average of 1 mol -SH per mol sIgA under nondenaturing conditions, whereas an average of 7.5 mol -SH was found under denaturing conditions. These -SH groups were found in both the sIgA-f and sIgA-g subclasses; in the sIgA-g subclass, the free -SH groups were found in the Fab alpha portion but not in the Fc alpha portion of the molecule. To determine whether the noncovalently bound polypeptide chains in sIgA contained free -SH groups, sIgA was alkylated with 14C-iodoacetamide and subjected to gel filtration in 6 M guanidine-HCl. This treatment liberated several different polypeptides that were identified as secretory component (SC), L chain dimers, and L chain monomers; measurement of radioactivity incorporated in each of these noncovalently bound chains showed that SC and the L chain dimers did not contain free -SH groups but that an average of 1 -SH group per L chain monomer was found. Of the covalently bound polypeptide chains, J chain and SC did not have detectable -SH groups, whereas the L chains and alpha-chains had 0.3 and 1.2 mol -SH per mol protein, respectively. The identification of free -SH groups in the Fab portion of the sIgA-g subclass and their preferential localization within only some of the L chains reflect the structural heterogeneity of sIgA; these -SH groups presumably arise during biosynthesis.

Animals↗
PubMed1979

Exclusion of VHa and VHy loci expression on individual B cells from normal and VH allotype-suppressed rabbits.

The distribution of two heavy chain subgroups, VHa and VHy, on rabbit peripheral blood lymphocytes was examined by double membrane immunofluorescence. Fluroescent anti-a1 and anti-y33 were found to react with separate B cell populations; no doubly stained cells were observed. Further evidence for the independent expression of genes controlling the VHa and VHy subgroups were obtained by neonatal suppression of a 2 or y33 in a2y33/a3y- heterozygous rabbits. Suppression of VHa did not affect the expression of VHy, nor did the suppression of VHy affect the expression of VHa. The expression of a single VH gene per B cell is in marked contrast to the simultaneous expression of multiple CH genes.

Aging↗
PubMed1979

Kinetics of escape from suppression of Ig heavy chain allotypes in multiheterozygous rabbits.

Three rabbits of genotype a1n81f73g74/a2n82f71g75 which had been injected at birth with anti-a l (VH) antiserum and which were previously shown to be suppressed for the paternal allotypes a 1, n81, f73 and g74 at 8 weeks of age, were monitored over a 2-year period for the concentration of suppressed and nonsuppressed allotypes in their sera. In all three suppressed animals, the f73 (C alpha) and g 74 (C alpha) allotypes were expressed again at a much greater rate than the a1 (VH) and n81 (C mu) allotypes. In one suppressed animal, the a l (VH) allotype was re-expressed at a much greater rate than the n81 (C mu) allotype and reflected primarily the reappearance of a l IgG. Thus, the escape from allotype suppression in this animal was in the order IgA, IgG, IgM which is the reverse of the order of appearance of these Ig classes during ontogeny. While the al(VH) and n81 (C mu) allotyes remained suppressed, the f73 (C alpha) and g74 (C alpha) allotypes were re-expressed to the same concentration as in the unsuppressed controls, and no compensatory decrease of the f71 and g75 allotypes occurred. During the re-expression of the f73 and g74 allotypes, the ratio of the concentrations of f73/g74 remained approximately constant.

Animals↗
PubMed1979

Expression of an unidentified immunoglobulin isotype on rabbit Ig-bearing lymphocytes.

A non-IgM immunoglobulin molecule was found on most rabbit Ig-bearing lymphocytes isolated from mesenteric lymph nodes. Membrane bound immunoglobulin light chains and heavy chains were detected by immunofluorescence and by rosetting with antibody-coated erythrocytes on mesenteric lymph node cells stripped of IgM by anti-IgM allotype antibodies. The percentage of cells bearing these residual immunoglobulin molecules was similar to the percentage of cells bearing immunoglobulin before "stripping" with anti-IgM antibody. These residual immunoglobulin molecules were not IgA nor IgG and are believed to be the rabbit analogue of human IgD.

Animals↗
PubMed1979

Heavy chain variable region allotypic subspecificities of rabbit immunoglobulins. II. Selective escape of the a1-AB Ig subpopulation after the induction of auto anti-a1 antibody.

An a1a2 rabbit (P286-3), neonatally suppressed for the expression of the a1 allotype, was immunized with autologous a1 IgG at 2 months of age. Both auto anti-a1 Ab and a1 IgG molecules were found in the serum of this rabbit after the auto-immunization. The auto anti-a1 Ab and the IgG from the auto anti-a1 Ab-depleted serum were isolated. Of the previously defined a1-AB, a1-AC, and a1-AD Ig subpopulations, the a1 IgG in the IgG preparation from the rabbit P286-3 were all of the a1-AB Ig subpopulation. The auto anti-a1 Ab from rabbit P286-3 did not react with the a1-A, a1-B, and a1-C allotypic subspecificities; thus, it was presumably specific for the a1-AC and a1-D allotypic subspecificity. Thus, the a1-AB Ig subpopulation escaped from allotype suppression in rabbit P286-3, whereas the a1-AD Ig subpopulation remained suppressed. The a1-AD Ig subpopulation will probably remain suppressed for a long time and perhaps permanently since rabbit P286-3 has produced circulating auto-Ab specific for the a1-D allotypic subspecificity. These results indicate that the a1 Ig subpopulations are synthesized by distinct clones of lymphocytes under separate control.

Aging↗
PubMed1979

EMG comparison of quadriceps femoris activity during knee extension and straight leg raises.

Both knee extension and straight leg raises have been used to rehabilitate atrophied quadriceps musculature following knee immobilization. A comparison of the tension developed during these two exercises was made in each of the three surface quadriceps muscles (quadriceps femoris, vastus lateralis, vastus medialis) at three different levels of activity (20%, 50%, and 80% of 1RM). Integrated EMG (m Volt-seconds) was used to measure tension developed during a seven second contraction. Tension developed was significantly greater during a seven second contraction. Tension developed was significantly greater during knee extension than during straight leg raises at each exercise intensity. For both exercises and at all three exercise levels, the vastus lateralis was the most active; the vastus medialis was the least active. The difference between knee extension and straight leg raises became greater with increasing levels of activity. Therefore, unless contraindicated by chondromalacia of lack of knee flexibility, knee extensions should be used for post-surgical knee rehabilitation. The greater tension development would lead to a more rapid return of strength, and therefore quicker rehabilitation.

Action Potentials↗
PubMed1978

Serologic and structural comparisons of rabbit IgA allotypes.

Serologic and structural comparisons of the rabbit IgA-g allotypes revealed that 1) the IgA-g allotypes have multiple allotypic determinant sites, 2) the g74, g76 and g77 allotypic specificities have several allotypic determinants in common whereas g75 molecules do not appear to have allotypic determinants in common with g74, g76 and g77 molecules, 3) the partial amino acid sequence of alpha chain from g75 and g76 Fc2alpha fragments differ by at least one amino acid residue, and 4) the g74 alpha-chains may have the "extra" intradomain disulfide bond in the Calpha2 domain whereas the g75 and g76 alpha chains lack this disulfide bond. Thus, multiple mutational events must have occurred during the evolution of g74, g75 and g77 genes.

Amino Acid Sequence↗