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I Todd

Publications and source records attributed to I Todd.

At least 73 records · Page 4Linked to original sources
PubMed1986

HLA-D/DR expression on epithelial cells: the finger on the trigger?

The findings we have described here show a clear association between epithelial HLA-D/DR expression and autoimmunity. Furthermore, the ability of class II+ thyrocytes to present both exogenous antigens and autoantigens indicates an active role for these HLA-D/DR molecules in autoimmune pathogenesis. IFN-gamma is capable of inducing HLA-D/DR expression by thyroid epithelium, but a number of observations suggest the involvement of other inducers as well. Overall, we conclude that epithelial class II expression very probably plays a key role in the propagation and also in possibly the initiation of autoimmune attack. This is in accord with the proposal of a more general relationship between inappropriate or excessive class II expression and pathogenesis.

Antigen-Presenting Cells↗
PubMed1986

Inappropriate major histocompatibility complex class II expression by thyroid follicular cells in thyroid autoimmune disease and by pancreatic beta cells in type I diabetes.

"Inappropriate" expression of class II major histocompatibility complex (MHC) molecules by target cells has been found in all organ-specific autoimmune diseases so far examined for the presence of this phenomenon. These glycoproteins may have a functional role as class II+ thyrocytes are able to present both small fragments of foreign antigens and autoantigens to helper T cells. Interferon gamma is a likely modulator of MHC class II expression in the thyroid but other signals like thyroid-stimulating hormone seem to influence its action. By contrast, it appears that lymphokines are not involved in inducing the inappropriate MHC class II expression observed in situ in the pancreatic beta cells of diabetics. These data suggest that regulation of MHC class II expression is different in thyroid follicular cells from pancreatic beta cells, and that similar differences may be found in other cell types involved in autoimmune disease, thus reinforcing the concept of heterogeneity in the pathogenesis of organ-specific autoimmune disorders.

Antigen-Presenting Cells↗
PubMed1986

Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas.

Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes.

Cells, Cultured↗
PubMed1985

Immunologic memory to phosphorylcholine. VI. Heterogeneity in light chain gene expression.

BALB/c mice immunized with phosphorylcholine-conjugated keyhole limpet hemocyanin (PC-KLH) produce two types of anti-PC antibodies, designated group I and group II, which differ in their fine specificity and idiotype expression. Group II hybridomas can utilize VH genes and VL genes (in particular, V kappa 1-3) distinct from those expressed in the group I-like anti-PC myelomas. Here we have analyzed additional anti-PC hybridomas from BALB/c and (CBA/N X BALB/c)F1 male mice and also anti-PC antibodies purified from BALB/c and C57BL/6N antisera. Isoelectric focusing indicates that one of the group II hybridomas utilizes V kappa 1-3 and that related L chains are expressed in a major portion of group II serum antibodies. Other group II antibodies in antisera express different L chains, some of which are presently unidentified. However, isoelectric focusing analysis also indicates that the L chains of some group II hybridomas and serum antibodies are related to those found in the group I anti-PC myelomas and group I hybridoma and serum antibodies. In addition, one hybridoma was found to utilize lambda 2. Thus, it appears that the anti-PC antibodies with group II-like fine specificity can utilize a variety of VL genes related to, or distinct from, those expressed in group I antibodies.

Animals↗
PubMed1985

Topography of cell-glass apposition revealed by total internal reflection fluorescence of volume markers.

We have developed a new method based on total internal reflection fluorescence to map the shape of the region between glass and the lower surface of a living cell spread upon it. Fluorescently labeled nonadsorbing volume marker molecules that cannot penetrate into the cell are locally stimulated so that they fluoresce only very near the glass/medium interface. The total fluorescence intensity at any point beneath the cell depends on the cell-to-glass separation. Focal contacts appear as dark areas owing to dye exclusion, whereas when the gap exceeds approximately 150 nm, fluorescence asymptotes to the bright background level. Our technique provides greater contrast than does interference reflection microscopy and is free from errors due to cytoplasmic thickness and refractive index inhomogeneities arising from cytoplasmic inclusions. We have shown that sufficiently large molecules suffer steric exclusion from regions accessible to small molecules, which gives new information about lateral penetrability in the apposition region.

Animals↗
PubMed1985

Pacemaker discomfort induced by the wearing of seat belts.

A survey was made of 100 consecutive pacemaker recipients to examine problems they may have experienced with seat belts whilst travelling by car, either as drivers (29 patients) or front seat passengers (50 patients). Twenty-one per cent of the drivers and 30% of the front seat passengers had experienced symptoms, usually of a mild nature. Re-siting of the generator was only necessary in 1 patient and no example of electrode displacement was observed. Suggestions are made as to how this problem might be overcome.

Adipose Tissue↗
PubMed1985

Interferon-gamma induces HLA-DR expression by thyroid epithelium.

We recently showed that human thyroid epithelial cells, which are normally negative for HLA-DR molecules, express HLA-DR in thyroid autoimmunity. Furthermore, induction of HLA-DR on normal thyroid cells can be achieved by culture with plant lectins. We have now found that recombinant human interferon-gamma (IFN-gamma) induces expression of HLA-DR molecules on cultured human thyroid cells, whereas Namalva IFN-alpha, recombinant IFN-beta or recombinant interleukin-2 (IL-2) do not. All three IFN, but not IL-2, enhanced thyroid cell HLA-A,B,C expression. The results strongly implicate T cells (which are the source of IFN-gamma) in the aberrant induction of DR on thyroid epithelial cells which is proposed to be a central feature of the immunopathological processes leading to autoimmunity.

Cells, Cultured↗
PubMed1984

A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease.

This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.

Adult↗
PubMed1984

Immunologic memory to phosphocholine. V. Hybridomas representative of group II antibodies utilize V kappa 1-3 gene(s).

The anti-phosphocholine (PC) memory response of BALB/c mice to PC-KLH contains two groups of antibodies distinguished by fine specificity and by expression of the T15 idiotype that dominates Group I but not Group II anti-PC antibodies. The contribution of V kappa genes to this diversity was investigated by the analysis of L chains from PC-binding hybridoma proteins (PCBHP) representative of Group I and Group II. N-terminal amino acid sequence analysis was performed on the L chains of three independently derived Group II PCBHP up to residue 23 (PCG1-1) or 21 (aPC-111-1 and aPC-12-3). These three sequences differed from each other by only one or two residues, but differed by approximately 50% from the L chains of the Group I-like PC-binding myeloma proteins (PCBMP); the Group II sequences are closely related to V kappa 1-3. Isoelectric focusing analysis was also performed on the L chain of PCG1-1, as well as on L chains from PCBHP typical of Group I antibodies, and from an atypical PCBHP differing from Groups I and II in fine specificity. A Group I PCBHP and the atypical PCBHP expressed L chains related to V kappa 8 and V kappa 24, respectively. The L chains of another Group I PCBHP and of the Group II protein, PCG1-1, appeared different from those found in the PCBMP and from each other. The results indicate a more diverse expression of L chains in the memory anti-PC response than is represented by the PCBMP; both V kappa 8- and V kappa 24-derived L chains (and, presumably, somatic variants), as well as products of additional V kappa genes (V kappa 1-3), appear to be present in the anti-PC memory pool.

Amino Acid Sequence↗
PubMed1983

The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease.

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.

Adolescent↗
PubMed1982

The effects of Hodgkin's disease and combination chemotherapy on gonadal function in the adult male.

The effects of Hodgkin's disease and quadruple chemotherapy on gonadal function have been investigated in 92 male patients with Hodgkin's disease. Nineteen men were studied before they received chemotherapy. Fifteen of the 19 had a sperm count of 20 million/ml or greater and motility was at least 40% in all 15. In the remaining 74 men, gonadal function was studied after completion of chemotherapy (6 months--8 years). Semen was obtained from 49 men who had received six of more courses of MVPP. Forty-two were azoospermic and five of the remaining seven had a sperm count below 1 million/ml. Decreased libido and sexual activity was common during treatment but in the majority of men these returned to normal after completion of chemotherapy. The median FSH and LH levels and the median increments in serum FSH and LH levels after LHRH administration were significantly elevated compared with an age-matched control group. The mean testosterone level of the patients was significantly lower than in controls suggesting Leydig cell damage but androgen replacement therapy was not indicated in any individual patient. No evidence of hyperprolactinaemia as a result of MVPP therapy was found. These results suggest that sperm storage before chemotherapy represents the main possibility for these patients to have children after completing chemotherapy. Before starting chemotherapy, advice should be given to these patients concerning possible changes in sexual behavior during treatment and the very high incidence of permanent infertility following treatment.

Adult↗
PubMed1982

Interaction between intracellular vacuoles and the cell surface analysed by finite aperture theory interference reflection microscopy.

Using finite aperture theory we have shown that localized very dark areas in the interference reflection images of Dictyostelium discoideum amoebae are due to the close intracellular approach of vesicles and tubular elements of the contractile vacuole system to the plasma membrane adjacent to the substratum. Vesicles interacting in this way become locally deformed to the planar contour of the substratum and are separated from the cell surface membrane by a constant approximately less than 0.1 micron of cytoplasm. Lamellar processes formed by these cells on very adhesive surfaces have identical dimensions. This minimal thickness may be a mechanical consequence of a contractile mechanism which pulls membranes together.

Animals↗
PubMed1982

Specific suppression of antibody responses in vivo. I. Effects of in vitro produced suppressor factor.

KLH-specific suppressor factors produced in vitro efficiently diminished primary and secondary responses to trinitrophenyl keyhole limpet haemocyanin (TNP-KLH) in vivo. Both IgM and IgG responses were approximately equally affected, These suppressor factors were not genetically restricted, as allogeneic suppressor factors worked as efficiently as syngeneic factors. Furthermore, xenogeneic human suppressor factors were effective in mice and suppressed the responses as efficiently as syngeneic factors. The kinetics of the response in suppressed and non-suppressed mice was the same, indicating that the magnitude of the response was affected and not merely its time course. Prior injection with suppressor factor did not cause suppression of response, while suppressor factor injected at the same time as or soon after the antigen did, suggesting that it might act at the effector stage. The mechanism of action of this unrestricted suppressor factor, and the use of mouse model for in vivo testing of human suppressor factors is discussed.

Animals↗
PubMed1980

Red blood cell adhesion. I. Determination of the ionic conditions for adhesion to an oil-water interface.

We have examined the adhesion of glutaraldehyde-treated human red blood cells to a clean liquid hydrocarbon interface as a function of sodium chloride concentration. Cells adhere reversibly to the interface over a wide range of concentrations but fail to do so below about 0.1 mM. Adherent cells do not alter the tension of the oil/water interface. These results show that cells can adhere by physical forces in special situations without biochemical interactions. The data provide a basis for calculating the size of the physical forces.

Alkanes↗
PubMed1980

Red blood cell adhesion. II. Interferometric examination of the interaction with hydrocarbon oil and glass.

Using both living and glutaraldehyde-fixed red cells, we have examined adhesion to both oil/saline and glass/saline interfaces by interference reflection microscopy. At low ionic strength, 0.4 mM NaCl, fixed cells adherent to the oil/saline interface show first order whitish yellow zones of closest approach which indicate a separation of similar to or approximately 100 nm. Quantitative interferometry in monochromatic light supports this conclusion. As the salt concentration is increased the separation decreases and the final image shows zero-order black which probably indicates molecular contact with the interface. Similar but less reproducible results were obtained with fixed and unfixed cells on glass. Thes observations show that physical interactions alone can be responsible for adhesion in dilute and concentrated salt solutions. It is not, however, believed that the results necessarily imply the existence of adhesion with a gap in physiological concentrations of salt.

Alkanes↗