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Biomedical subjects

J M Holmes

Publications and source records attributed to J M Holmes.

At least 73 records · Page 4Linked to original sources
PubMed1981

A 125IUdR technique for measuring the cell loss from subcutaneously growing canine transmissible venereal tumours.

A technique for measuring the cell loss from subcutaneous canine transmissible venereal tumours (TVT) has been devised. The tumour-bearing animal is injected with the intranuclear label 125 Iododeoxyuridine (125IUdR). By excising tumours at intervals and measuring their radioactive content per unit weight, an estimate of potential doubling time and so of cell loss can be made. Results using this technique compare well with previous estimates of the cell loss from TVT using the much more laborious labelled mitoses technique. Estimates of the effect of treatment on cell loss can also be made. Radio-therapy, specific passive immunotherapy and intravenous BCG inoculation were also shown to increase TVT cell death. Despite some innate mathematical inaccuracies and assumptions, this technique offers many advantages over conventional methods of estimating cell loss.

Animals↗
PubMed1976

Use of thyrotropin and cholera toxin to probe the mechanism by which interferon initiates its antiviral activity.

Thyrotropin (10 muM) inhibited the antiviral activity of interferon. When added after interferon, thyrotropin (TSH) had no effect on antiviral activity. There was also no inhibition of interferon action in cells washed with medium between incubations with TSH and interferon. 125I-Labeled TSH and 125I-labeled cholera toxin could bind to preparations of mouse L-cell plasma membranes. The binding was specific in that it was prevented by unlabeled thyrotropin or cholera toxin, but not by insulin, glucagon, prolactin, growth hormone, human chorionic gonadotropin, or luteinizing hormone. Mouse interferon inhibited 125I-labeled TSH binding to L-cell plasma membranes. The effect of mouse interferon on 125I-labeled cholera toxon binding was more complex, inhibition occurring only after an initial enhancement at low interferon concentrations. A 10-fold higher concentration of interferon was required to inhibit 125I-labeled TSH binding. Mouse interferon was also able to displace bound 125I-labeled TSH, but not bound 125I-labeled cholera toxin. The interferon interaction with cell membranes was temperature-sensitive. Human interferon could induce changes in binding of 125I-labeled TSH and 125I-labeled cholera toxin to mouse L-cell plasma membranes similar to those induced by mouse interferon. Mouse interferon induced similar changes in plasma membranes of human KB-3 cells, which are insensitive to both human and mouse interferons. In view of these results, the species specificity of interferons does not appear to reside solely at the point of the initial interaction with their binding sites.

Bacterial Toxins↗
PubMed1975

Thyrotropin receptors in thyroid plasma membranes. Characteristics of thyrotropin binding and solubilization of thyrotropin receptor activity by tryptic digestion.

Biologically active bovine 125I-thyrotropin preparations have been prepared, characterized, and used to evaluate the optimal conditions for thyrotropin binding to bovine thyroid plasma membranes in vitro. Binding of 125I-TSH has a pH optimum around 6.0 and is sensitive to the choice and concentration of buffer. Binding is inhibited by salts, especially those containing magnesium and calcium ions; magnesium concentrations optimal for adenylate cyclase assays (2 to 5 mM) result in 85 to 98% inhibition of binding. Binding is temperature sensitive. At 37 degrees binding has its highest initial level; however, instability of the membrane at this temperature causes a rapid loss of binding activity. Binding at 0 degrees is optimal in 30 min and at the same level as initial binding at 37 degrees; since there is no decrease in binding activity, it has been chosen as the optimal temperature. Thyrotropin, luteinizing hormone, the beta subunit of thyrotropin, and the alpha subunit of thyrotropin have relative binding affinities for the thyrotropin receptors of 100, 10, 2, and less than 0.5, respectively. In all of these characteristics, 125I-thyrotropin at 1.5 x 10(-5) M concentrations has the same properties of binding to bovine plasma membranes as do [3H]thyrotropin preparations which have been previously characterized (Amir, S.M., Carraway, T.F., Jr., Kohn, L.D., and Winand, R.V. (1973) J. Biol. Chem. 248, 4092-4100) and used to study binding at 5 x 10(-6) M concentrations. 125I-TSH binding as a function of hormone concentration results in curved Scatchard plots; however, Hill plots of these same binding data are linear and have a slope of 0.65. Taken together, these data suggest that the heterogeneity in thyrotropin binding constants which is evident in the Scatchard plot reflects a negatively cooperative relationship among the thyrotropin receptor sites, i.e. decreased hormonal affinity as hormone concentrations increase. Adenylate cyclase studies yield kinetic plots which also exhibit negative cooperativity; corrections for thyrotropin bound under the adverse binding conditions of the adenylate cyclase assays suggest that Km values for thyrotropin in this enzymatic assay are compatible with binding constants measured by the 125I-thyrotropin preparations. Tryptic digestion destroys binding activity on the thyroid plasma membrane but releases specific thyrotropin receptor activity into the supernatant phase. Chromatography on Sephadex G-100 indicates that this solubilized receptor fragment has a molecular weight between 15,000 and 30,000.

Adenylyl Cyclases↗
PubMed1975

Characteristics of a solubilized thyrotropin receptor from bovine thyroid plasma membranes.

The thyrotropin receptor from bovine thyroid plasma membranes has been solubilized using lithium diiodosalicylate, and an assay to measure thyrotropin binding to the solubilized receptor has been developed. Both the solubilized thyrotropin receptor and the thyrotropin receptor on thyroid plasma membranes have effectively identical nonlinear Scatchard plots and negatively sloped Hill plots, i.e. both preparations have receptors which appear to exhibit a similar negatively cooperative relationship. Although the pH optimum of thyrotropin binding to the solubilized receptor is the same as that of the thyroid plasma membrane receptor, pH 6.0, the pH dependency curve of the solubilized receptor is slightly different in its outline. Thyrotropin binding to the solubilized receptor is less sensitive to salt inhibition than is binding to the thyroid plasma membrane receptor; however, optimal binding remains at 0 degrees. The relative affinities of thyrotropin and two glycoprotein hormones which can be considered structural analogs, luteinizing hormone and human chorionic gonadotropin, are 100:10:5, respectively, toward plasma membrane receptors, but 100:25:40 toward the solubilized receptors. The solubilized receptor preparation is heterogeneous in size in that it has binding components with molecular weights of 286,000, 160,000, 75,000, and 15,000 to 30,000. Tryptic digestion converts all three higher molecular weight components to the 15,000 to 30,000 molecular weight species, and the 15,000 to 30,000 molecular weight receptor component has all of the binding properties of the solubilized receptor preparation before tryptic digestion including an identical nonlinear Scatchard plot. It has the same size as and coelutes from Sephadex G-100 with a 15,000 to 30,000 molecular weight receptor released by tryptic digestion of bovine thyroid plasma membranes or tryptic digestion of bovine or dog thyroid cells in culture. The tryptic fragment of the solubilized receptor or preparations has been purified almost 250-fold by affinity chromatography on thyrotropin-Sepharose columns. The binding activity is lost when the solubilized thyrotropin receptor preparation is exposed to beads of neuraminidase-Sepharose or conconavalin A-Sepharose.

Animals↗
PubMed1975

Fact and theory in recovery from the aphasias.

Clinical evidence has suggested that the form of an aphasia--and perhaps potential for recovery therefrom--can be related to an exceedingly wide range of variables. Such anatomico-physiological considerations as size, depth, location and nature (e.g. penetrating missile injury, stroke, tumour, closed head injury) of the injury are frequently held to be crucial correlates, as are associated neurological deficits (e.g. presence of hemiplegia, sensory and visual field defects). Subject variables, such as age, sex and 'handedness" (including familial handedness), complicate the picture still further, as may differences in education personality and cognitive style. Given a multidimensional problem of this magnitude the first objective of theory is to indicate putative constrainst on patterns of impaired performance. Studies of the normal population--that is, the population from which cases of brain injury are later drawn--may, we believe, aid in the elucidation of individual differences seen after injury. A more detailed knowledge of the range of possibilities concerning cerebral specialization of function and variations in task strategies seems to be required. In this context we shall review some recent reports on dichotic listening and split visual field experiments with both normal and brain-damaged subjects and also consider the role that linguistic descriptions of aphasic impairment could play in suggesting retraining procedures appropriate to the individual patient.

Aphasia↗
PubMedDate not supplied

Couples' perceptions of effective and ineffective ingredients of marital therapy.

Reports from 15 couples of the helpful and hindering aspects of their marital therapy were sorted into 12 effective ingredient categories and 5 ineffective categories. The couples were interviewed after receiving eight sessions of marital therapy. Results indicate that couples expect marital therapists to be active, directive, and focused while providing a safe and empathic therapeutic environment. Also, couples identified therapist mistakes such as wasting time and being unclear in therapy as detrimental to therapy. The implications of these empirically derived processes for the theory, research, and practice of marital therapy are discussed.

Adult↗
PubMedDate not supplied

Assessment of visual acuity in children with trisomy 18.

Although 90% of children with trisomy 18 (Edwards syndrome) die in the first year of life, a small proportion survive into the second and third decade. Many do not have associated ocular abnormalities that might affect vision. Measurable visual acuity has not been reported in these profoundly developmentally delayed individuals. Five children with trisomy 18, aged six months to eight years, underwent complete eye examination including assessment of binocular grating acuity with Teller acuity cards and assessment of binocular vernier acuity with vernier cards. All children were nonverbal with profound developmental delay. Binocular grating acuity ranged from 0.9 cycles per degree (cpd) to 2.2 cpd. This represents a reduction of 1.9 to 5.1 octaves (mean 3.5 octaves, SD 1.3 octaves) compared to age matched norms. None of the children responded to any of the vernier offsets, including the largest of 64 minutes of arc. All children with trisomy 18 demonstrated a measurable grating acuity that was well below normal for age, consistent with profound developmental delay.

Child↗