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Biomedical subjects

J M Holmes

Publications and source records attributed to J M Holmes.

At least 55 records · Page 3Linked to original sources
PubMed1992

Role of antigen-specific T cell help in the generation of in vivo antibody responses. II. Sustained antigen-specific T cell help is required to induce a specific antibody response.

The injection of mice with a goat or rabbit antibody to mouse IgD stimulates a large polyclonal IgG response, approximately 10% of which is specific for antigenic determinants on the anti-IgD antibody molecule. The large goat IgG (GIgG)-specific antibody response in mice injected with goat antibody to mouse IgD requires that GIgG-specific B cells undergo much greater clonal expansion than B cells specific for other Ag. One possible explanation for the greater clonal expansion of GIgG-specific B cells is that B cells that lack GIgG specificity can only be stimulated with GIgG-specific T help during the relatively short time that anti-IgD binds to, and is processed and presented by, these B cells before they cease to express membrane mIgD. In contrast, GIgG-specific B cells can continue to bind, process, and present GIgG through mIgM after they lose mIgD. To test the hypothesis that extended stimulation with Ag-specific T help is required to generate a specific antibody response, we determined time requirements for Ag-specific T cell help for the development of such a response. Mice were injected with rabbit antibody to mouse IgD plus one or more daily injections of FITC conjugated to a F(ab')2 fragment of rabbit IgG (FITC-(Fab')2), which has a short in vivo half-life, and IgG1 anti-FITC antibody production was analyzed. In this system, each additional injection of FITC-F(ab')2 extends the period during which FITC-specific B cells can process this Ag and present it to rabbit IgG-specific T cells. Each additional injection of FITC-F(ab')2 stimulated a several-fold increase in IgG1 anti-FITC antibody levels, and injections on 5 consecutive days were required to induce a maximal anti-FITC response. These observations provide evidence that sustained Ag-specific T cell help is required to stimulate the degree of B cell clonal expansion that characterizes a specific antibody response.

Animals↗
PubMed1992

The effect of arm exercise and ocular massage on postural hand tremor.

In this pilot study, the effect of exertion on hand tremor was investigated. Postural head tremor was measured in eight ophthalmology residents before and after lifting a barbell and before and after massaging a phantom eye. All subjects showed an increase in postural hand tremor after lifting a barbell for five minutes (mean, 79% +/- 59%). Postural hand tremor increased 38% +/- 79% after ocular massage, which was not statistically significant (P greater than .5). The peak pressures generated during ocular massage ranged from 25 to 265 mmHg (mean, 134 +/- 80.4 mmHg). There was also no correlation between change in postural hand tremor and the pressure generated by ocular massage (P greater than .2). The authors conclude that strenuous arm exercise, such as lifting a barbell, increases postural hand tremor and should be avoided before doing microsurgery; ocular massage is not sufficient exercise to affect postural hand tremor adversely.

Arm↗
PubMed1991

The effect of preoperative flurbiprofen on miosis produced by acetylcholine during cataract surgery.

Sustained pupillary dilation during cataract surgery may be achieved with preoperative noncorticosteroidal anti-inflammatory agents such as flurbiprofen. However, these agents may interfere with miosis after injection of acetylcholine. Thirty patients for extracapsular cataract extraction were randomly assigned in a double-masked fashion to receive either a placebo or preoperative 0.03% flurbiprofen every 30 minutes for four doses. All patients also received three doses of 2.5% phenylephrine and 2% cyclopentolate. Pupillary diameter was measured the day before surgery, immediately before the surgical incision, immediately before and five minutes after acetylcholine injection, and the morning after surgery. The flurbiprofen group had a larger mean pupillary diameter before injection of acetylcholine (P less than .001), five minutes after acetylcholine (P less than .001), and on the first postoperative day (P less than .005).

Acetylcholine↗
PubMed1991

Polyclonal activation of the murine immune system by an antibody to IgD. XI. Contribution of membrane IgD cross-linking to the generation of an in vivo polyclonal antibody response.

The injection of mice with a foreign, polyclonal antibody to IgD sequentially induces: 1) activation of B cells by cross-linking of their cell membrane (m) IgD; 2) B cell processing and presentation of the bound anti-IgD antibody to T cells; 3) activation of these T cells; and 4) T-dependent stimulation of B cell differentiation into IgG1 secreting cells. To determine whether the cross-linking of B cell membrane IgD and/or the resulting B cell activation that follows contribute to the generation of the polyclonal IgG1 response, we examined the abilities of three sets of anti-delta mAb or mAb fragments to stimulate polyclonal IgG1 production. Within each set mAb were matched for species and Ig isotypic determinants, but differed in avidity for IgD or in ability to cross-link IgD. In addition, experiments were performed to determine whether the anti-delta mAb had to be foreign to the immunized mouse to stimulate an IgG1 response. Results of these experiments indicate that: 1) recognition of the injected anti-delta antibody as foreign is required for the induction of a polyclonal IgG1 response; 2) the cross-linking of B cell membrane Ig, which directly activates B cells, can contribute considerably to the generation of in vivo IgG1 production; and 3) that even relatively weak cross-linking of membrane Ig by ligands that bind it with low avidity can make this contribution.

Animals↗
PubMed1991

Effects of topical suprofen and flurbiprofen on the miosis produced by anterior chamber irrigation with cholinergic agonists.

Pretreatment with topical nonsteroidal anti-inflammatory drugs is common practice to maintain maximal pupil dilation for cataract surgery. Most surgeons also inject a cholinergic agent intracamerally for miosis after intraocular lens insertion. We evaluated the effects of topical suprofen and flurbiprofen on the miosis induced by anterior chamber irrigation with either acetylcholine or carbachol. One eye of 30 pigmented rabbits was dilated with cyclopentolate HCl and phenylephrine HCl. Three groups, each composed of ten eyes, received flurbiprofen, suprofen, or a control. In each group, five eyes received acetylcholine by anterior chamber irrigation and five received carbachol. Pupil diameters were measured with calipers before and five minutes after irrigation by an observer unaware of the treatment regimen. Irides irrigated with carbachol constricted less than those irrigated with acetylcholine (P = .016). In anterior chambers irrigated with carbachol, suprofen was associated with less miosis than either tears (P = .005) or flurbiprofen (P = .009); however, if the infusion was performed with acetylcholine, no differences between the three groups were noted (P = .44).

Acetylcholine↗
PubMed1991

Regulation of murine in vivo IgG and IgE responses by a monoclonal anti-IL-4 receptor antibody.

Although the cytokine interleukin 4 (IL-4) stimulates LPS-activated mouse B lymphocytes to secrete both IgG1 and IgE, an anti-IL-4 antibody completely inhibits IgE responses but has little or no effect on several in vivo IgG responses. IL-4 might, therefore, have a restricted role in the generation of in vivo humoral immune responses. Alternatively, IgG1 responses might be stimulated by IL-4 secreted by T cells that are interacting directly with B cells, so that anti-IL-4 antibody cannot neutralize IL-4 before it binds to a B cell IL-4 receptor. In contrast, an antibody that blocks the IL-4 receptor (IL-4R) should equally inhibit responses to IL-4 produced proximal to or distant from a B cell. This reasoning led us to determine the ability of an anti-IL-4R mAb to affect antibody production in mice injected with a goat antibody to mouse IgD (GaM delta) or inoculated with the nematode parasite Heligmosomoides polygyrus. Anti-IL-4R mAb, like anti-IL-4 mAb, blocked IgE responses by greater than 95% and enhanced IgG2a responses to a variable extent. Anti-IL-4R mAb, however, had only a modest and variable inhibitory effect on the induction of IgG1 responses, although it caused these responses to terminate more rapidly. A combination of anti-IL-4 and anti-IL-4R mAbs totally blocked goat anti-mouse IgD antibody (GaM delta)-induced IgE production but had no additive inhibitory effect on IgG1 production. These observations are most consistent with the view that IL-4 is required for a primary IgE response, but has relatively little role in the induction of IgG1 responses in the in vivo systems studied.

Animals↗
PubMed1990

Polyclonal activation of the murine immune system by an antibody to IgD. X. Evidence that the precursors of IgG1-secreting cells are newly generated membrane IgD+B cells rather than the B cells that are initially activated by anti-IgD antibody.

Injection of BALB/c mice with an affinity-purified goat antibody to mouse IgD (GaM delta) stimulates T cell-independent B cell activation as well as later T cell activation. Activated T cells then induce polyclonal differentiation of B cells into IgG1-secreting cells, which results in an approximately 100-fold increase in serum IgG1 level. It is not known whether the same B cells that are initially activated by GaM delta are the progenitors of the IgG1-secreting cells. To investigate this issue a system was developed in which CB20 mice, which are congenic to BALB/c mice but express Ig of the beta allotype rather than the BALB/c alpha allotype, were injected with GaM delta and simultaneously or subsequently also received BALB/c B cells. The IgG1 response generated by the donor BALB/c B cells was quantitated by an assay specific for IgG1 of the alpha allotype. Our experiments with this system indicate that: 1) BALB/c B cells transferred 2 days after CB20 mice were injected with GaM delta generate a much larger IgG1 response than do BALB/c B cells transferred simultaneously with GaM delta antibody; 2) B cells that express membrane IgD generate the great majority of this response; 3) differences in the magnitudes of the responses of BALB/c B cells transferred at different times after CB20 mice were injected with GaM delta antibody cannot be explained by differences in homing of the donor B cells to the host spleen or by short survival of donor BALB/c B cells after their transfer; and 4) the response made by donor BALB/c B cells transferred 2 days after CB20 mice were injected with GaM delta is proportionate to donor cell representation in the host spleen 1 day after their transfer, whereas the response made by donor cells transferred simultaneously with GaM delta is disproportionately small. These observations suggest that most of the IgG1 antibody made by GaM delta-injected mice is generated by newly produced, mIgD+ B cells that appear approximately 2 days after GaM delta injection, rather than by those B cells that are present in the spleen at the time of GaM delta injection, and support the view that signals that induce B cell secretion of Ig require an interaction with at least partially activated Th cells.

Animals↗
PubMed1990

Rapid stimulation of large specific antibody responses with conjugates of antigen and anti-IgD antibody.

Injection of mice with goat anti-mouse IgD antibody stimulates a large IgG1 anti-goat IgG antibody response, as well as polyclonal IgG1 production. To determine if this phenomenon could be used to induce large antibody responses to other Ag, covalent conjugates were produced between BSA or other Ag and H delta a/1, a mAb specific for IgD of the a allotype, and between BSA and AF3.33, a mAb specific for IgD of the b allotype. Injection of H delta a/1-BSA into BALB/c mice, which express Ig of the a allotype, or into (BALB/c x CB20)F1 mice (a x b allotype heterozygotes) induced IgG1 anti-BSA antibody responses that peaked 8 to 9 days after injection, and were more than 1000 times larger than those induced by injection of BSA alone, and 100 times larger than those induced by injecting unconjugated BSA plus H delta a/1. H delta a/1-BSA was no more immunogenic than unconjugated BSA when injected into CB20 mice, which express Ig of the b allotype, while AF3.33-BSA greatly enhanced anti-BSA antibody production in CB20, but not in BALB/c mice. Mice serially immunized with three different Ag conjugated to H delta a/1 made large antibody responses to all three Ag, provided that the mouse strain used did not recognize allotypic determinants on H delta a/1 as foreign and produce a neutralizing antibody response. Intravenous and s.c. routes of inoculation produced responses of similar magnitude and relatively low variability; responses to footpad or intramuscular inoculation were more variable, and i.p. inoculation induced smaller responses. Injection of BALB/c mice i.v. with 100 micrograms of H delta a/1-BSA induced an IgG1 anti-BSA response of 5.6 mg/ml, which was approximately 70% of the total IgG1 response. Anti-BSA responses to 30 micrograms of conjugate or less were much smaller, but could be considerably enhanced by adding unconjugated H delta a/1 to the inoculum. This system will be useful for the rapid stimulation of large antibody responses to biologically important Ag, and for investigating mechanisms of Ag processing and B and T cell activation.

Animals↗
PubMed1989

Uptake and distribution of transferrin and iron in perfused, iron-deficient rat liver.

Uptake of transferrin and iron by the rat liver was investigated by perfusion in vitro with 125I-59Fe-labeled rat transferrin and subcellular fractionation on sucrose density gradients. Most of the 125I-transferrin was located in a low-density vesicle fraction. The 59Fe was in three peaks, of lower, the same, and higher densities than the transferrin peak. Iron deficiency resulted in a large increase in transferrin and iron uptake into all subcellular fractions. When livers were perfused with increasing concentrations of transferrin the uptake into the different peaks of transferrin and iron increased in a curvilinear fashion, which indicated that uptake occurred by saturable and nonsaturable processes, both of which increased in iron deficiency. In contrast, the uptake of 131I-labeled rat serum albumin increased linearly with concentration, and there was no difference between control and iron-deficient livers. It is concluded that iron deficiency leads to an increase in the number of high-affinity transferrin receptors and receptor-mediated endocytosis of transferrin. It also increases a nonsaturable transferrin uptake process that is probably due to adsorptive, but selective, endocytosis of transferrin.

Animals↗
PubMed1986

Assessing children's memory productions of the Rey-Osterrieth Complex Figure.

This report describes developmental changes in children's memory productions of the Rey-Osterrieth Complex Figure and in the relation of memory to copy productions, and a method for evaluating these productions that is sensitive to parameters relevant to neuropsychological diagnosis. Based on protocols from a standardization sample of 454 children between the ages of 5 and 14 (Waber & Homes, 1985), a system was devised for objectively evaluating organization, production style, and accuracy. Normative findings are described and implications for the use of this instrument in the neuropsychological assessment of children discussed.

Adolescent↗
PubMed1985

Assessing children's copy productions of the Rey-Osterrieth Complex Figure.

This report describes developmental changes in children's copy productions of the Rey-Osterrieth Complex Figure as well as a new method for evaluating these productions that is sensitive to parameters relevant for neuropsychological diagnosis. Based on protocols from a standardization sample of 454 children between the ages of 5 and 14, a system was devised for evaluating objectively: organization; production style; and, accuracy. Normative findings are described and implications for the use of this instrument in the neuropsychological assessment of children discussed.

Adolescent↗
PubMed1985

The effects of piracetam in children with dyslexia.

Following previous research which suggests that piracetam improves performance on tasks associated with the left hemisphere, a 12-week, double-blind, placebo-controlled study of developmental dyslexics was conducted. Six study sites treated 257 dyslexic boys between the ages of 8 and 13 years who were significantly below their potential in reading performance. Children were of at least normal intelligence, had normal findings on audiologic, ophthalmologic, neurologic, and physical examination, and were neither educationally deprived nor emotionally disturbed. Piracetam was found to be well tolerated in this study population. Children treated with piracetam showed improvements in reading speed. No other effects on reading were observed. In addition, improvement in auditory sequential short-term memory was observed in those piracetam-treated patients who showed relatively poor memory at baseline. It is suggested that longer term treatment with piracetam may result in additional improvements.

Adolescent↗
PubMed1983

The toxicity of fluorodeoxyuridine when used to increase the uptake of 125I-iododeoxyuridine into tissue culture cells in vitro.

The use of fluorodeoxyuridine (FUdR) to increase the uptake of 125I-iododeoxyuridine (125IUdR) into tissue culture cells was investigated. FUdR was found to be chemically toxic in itself to 2 canine tissue culture lines at doses used in the literature to increase 125IUdR uptake. FUdR had a cytocidal effect on one cell line, but a cytostatic effect on the other, so that measurement of only cell viability or death in the latter would not have shown a toxic effect. FUdR was shown to mask the radiotoxic effects of 125IUdR and so its use in investigations of the toxicity of 125IUdR may have produced misleading results.

Animals↗
PubMed1982

Measurement of the cell loss from two spontaneous canine tumours.

Estimates of the cell loss from spontaneously occurring tumours in two dogs were made by the intranuclear isotope-labelling technique. The dogs were injected with 125iodine labelled iododeoxyuridine and tumour biopsies taken at intervals so that the potential doubling time of the tumours and the cell loss factor could be estimated from the radioactive content per unit weight. This is the first report of the use of this method with spontaneously occurring tumours in dogs. Cell loss factors of over 90 per cent were recorded in each case, correlating well with information obtained from other techniques for spontaneous human and canine tumours.

Animals↗
PubMed1981

Measurement of the rate of death of canine transmissible venereal tumour cells transplanted into dogs and nude mice.

An intranuclear isotope labelling technique in which the fate of cells labelled with I125-iododeoxyuridine (I125UdR) is monitored, has been adapted for use with dogs. The death rate of injected labelled cells is followed by measuring the appearance of label in the urine. Only a small proportion of injected labelled canine transmissible venereal tumour (TVT) cells survive to contribute to tumour formation when the TVT is transmitted by subcutaneous injection. TVT has also been grown in athymic nude mice and tumour was successfully retransferred to dogs from a nude mouse tumour. Using conventional I125UdR techniques, rapid death of the majority of TVT cells transplanted into nude mice was again encountered. The correlation of dog and nude mouse results emphasises the usefulness of the nude mouse as a model for investigating the kinetics of xenografted tumours.

Animals↗