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Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 199 records · Page 11Linked to original sources
PubMed1984

Vitamin D and femoral neck fractures in elderly South Australian women.

The vitamin D status of women with femoral neck fractures and of male and female nursing-home residents in South Australia was assessed and compared with that of ambulant normal elderly women and young male and female controls. Serum 25-hydroxyvitamin D (25OHD) was assayed with a competitive protein-binding method including a chromatography step. The mean serum 25OHD levels in the patients with femoral neck fractures (39.2 [SE 2.6] nmol/L) and in the nursing-home residents (28.9 [SE 1.3] nmol/L) were significantly lower than those in the ambulant elderly women (67.6 [SE 3.9] nmol/L) and young controls (76.9 [SE 3.7] nmol/L) (P less than 0.001 in each case). The serum 25OHD levels were unrelated to age in the normal ambulant subjects. There was a significant seasonal variation in the results of routine 25OHD assays performed in our laboratory, but no such variation was seen in the nursing-home residents. We conclude that vitamin D deficiency is common in housebound subjects, and that femoral neck fractures occur mainly in subjects who were housebound before the fracture.

Adult↗
PubMed1984

A role for Ia antigens in thymocyte binding by macrophages.

To investigate the membrane structures involved in cellular interactions between thymocytes and macrophages, the relative ability of different murine macrophage populations to spontaneously bind thymocytes was compared. Macrophages derived from the spleen or thymus bound three to four times the number of thymocytes than macrophages from peripheral blood, peritoneum, or bone marrow. This reflects differences both in the number of macrophages binding thymocytes and in the number of thymocytes bound per macrophage. The extent of binding seems to positively correlate with the number of Ia-positive macrophages contained in these populations, as based on previously published values. This was confirmed by showing that elimination of splenic Ia-positive macrophages with anti-Ia and complement treatment dramatically reduced thymocyte binding. In addition, mouse peritoneal washout macrophages incubated for several days with supernatant fluid from concanavalin A-stimulated spleen cells, which induce Ia-antigen expression, exhibited a marked increase in the number of macrophages that bound thymocytes and the number of thymocytes bound per macrophage. To determine if Ia antigens were directly involved in binding, spleen, thymus, or Ia-induced peritoneal macrophages were treated with a monoclonal anti-Ia antibody prior to the addition of thymocytes. Treatment with anti-Ia reduced binding by around 50%, whereas treatment with anti-H-2D antibody had no effect. Monoclonal anti-I-A and anti-I-E antibody treatments of macrophages both inhibited thymocyte binding to similar extents, and treatment of macrophages with both reagents together reduced thymocyte binding by 80%. These results indicate that thymocyte binding is in part dependent on macrophage Ia expression.

Animals↗
PubMed1984

Treatment of protracted diarrhea of infancy.

Ten patients with protracted diarrhea of infancy received either 8% or 16% of 130 calories/kg/day as amino acids. Patients were treated initially with total parenteral nutrition (TPN) and subsequently with an elemental diet. Nitrogen balance was better during TPN in those who received the higher amino acid intake. No differences were noted between groups in weight gain or restoration of muscle mass. Higher levels of serum urea nitrogen and alkaline phosphatase were noted in patients with the higher amino acid intake; cholestatic liver injury developed in two of these patients. The patients receiving the higher amount of amino acid demonstrated enhanced calciuria during TPN. Other than better nitrogen balance, no clinical benefits and more undesirable side effects were observed in patients receiving 16% amino acid calories.

Alkaline Phosphatase↗
PubMed1984

Relationships between physical fitness and risk factors for coronary heart disease in men and women.

The aim of the study was to examine the cross-sectional relationships between physical fitness and risk factors for coronary heart disease (CHD). Measurements were made of fitness (defined as predicted maximal oxygen uptake), blood pressure, total cholesterol, triglycerides, and glucose in 1500 healthy men and women aged 20 to 65 years. After controlling for the effects of age, physique, smoking, alcohol use and stress, by multiple regression analyses, it was found that fitter men had lower blood pressure, cholesterol, and triglycerides than less fit men, and fitter women had lower blood pressure than less fit women. However, these fitness/risk factor relationships were seen as weak trends, probably of minor clinical importance. It is emphasised that such cross-sectional data should not be interpreted as support for the popular claim that people who increase their fitness can expect to improve their CHD risk factor status.

Adult↗
PubMed1984

Neonatal cholestasis and hypopituitarism.

The diagnosis of optic nerve hypoplasia and hypopituitarism must be entertained in infants who present for evaluation of cholestatic jaundice, particularly if there is associated hypoglycaemia and wandering nystagmus. Although the hepatic dysfunction seems to resolve, the long term prognosis of liver disease in optic nerve hypoplasia remains unknown.

Cholestasis↗
PubMed1984

Identification of macrophage receptors for angiotensin: a potential role in antigen uptake for T lymphocyte responses?

To determine if macrophages express receptors for peptide antigens, guinea pig peritoneal exudate cells (PEC) were examined for their uptake of the octapeptide angiotensin II (AII). PEC were incubated with [3H]AII, with or without nonradioactive AII as a cold inhibitor, for varying lengths of time before harvesting to determine the cell-associated [3H]AII counts per minute. The PEC-associated [3H]AII increased from 90 to 120 min of incubation, then plateaued on additional incubation to 3.5 hr. Inclusion of nonradiolabeled AII into the culture decreased the cell-associated [3H]AII by 80 to 90% at all time points. The uptake of [3H]AII was temperature-sensitive, with maximum cell-associated [3H]-AII occurring at 37 degrees C and reduced uptake occurring at 4 degrees C. The association of [3H]AII with PEC was specific and saturable, and the inhibitory dose for reducing the cell-associated [3H]AII by 50% with nonradiolabeled AII was around 6 X 10(-6) M. Various AII analogs were also employed as inhibitors to determine the fine specificity of [3H]AII binding, and only those analogs with nonaromatic amino acid substitutions for the carboxyl terminal Phe8 showed reduced inhibitory activity, indicating that Phe8 is important for binding. Scatchard analysis of binding indicated that two classes of receptors interacted with AII: a low number of receptors with Ka approximately equal to 3.5 X 10(8) M-1, and a large number of relatively low affinity of binding showing a Ka approximately equal to 5 X 10(5) M-1. The cellular binding activity was associated with isolated PEC plasma membranes, and after density gradient fractionation of solubilized membranes, AII binding activity was primarily associated with molecules of m.w. of around 50,000. PEC were separated into macrophages and lymphocytes by adherence, and all of the [3H]AII binding activity was associated with the macrophage-enriched cells. These results show that macrophages express specific receptors for AII and related peptides that are responsible for most of the uptake of AII by macrophages. We discuss the relevance of this receptor for the immunologically important uptake of AII by macrophages, and a potential physiologic role in angiotensin-converting enzyme production.

Angiotensin II↗
PubMed1984

Macrophage processing of peptide antigens: identification of an antigenic complex.

In this report, we present data from our examination of the fate of the octapeptide antigen angiotensin II (AII) after processing by guinea pig macrophages. Macrophages were cultured with [125I]-AII or [3H]-AII for various times, and the AII products in the culture supernatant fluid and solubilized cell lysate (macrophage-associated AII) were analyzed by chromatography on Sephadex G-25. With [3H]-AII, both the cell-associated and cellfree AII was catabolized to three distinct peptide fragments: Peak B, containing seven to eight amino acids; Peak B1, with five to six amino acids; and Peak C, containing four to five amino acids. Surprisingly, in the cells another major form of AII was obtained, Peak A, which showed an m.w. of 50,000 to 70,000. Formation of Peak A was blocked by inclusion of non-radiolabeled AII into the incubation mixture, and could be formed by repulsing fresh macrophages with isolated Peaks B and B1, and to only a minor extent with Peak C. Peak A was formed within an hour of culture of macrophages with [3H]-AII, and remained stably cell-associated through a day of culture. In a pulse-chase type of experiment, it was shown that macrophages rapidly exocytose cell-associated Peaks B and C, and Peak B1 less rapidly, whereas Peak A is retained and is the predominant cell-associated form of AII after a day in culture. Incubation of [3H]-AII with isolated macrophage plasma membranes also resulted in Peak A formation, showing that the complex can be formed by a membrane event not requiring cellular uptake of peptide. The complex of AII in Peak A was acid-stable, and approximately 20% of Peak A was recovered after boiling in SDS. Because Peak A is the primary form of AII retained by macrophages, it was important to determine if this complex was antigenic for T cells. AII-immune T cells cultured with Peak A showed significant proliferation that was specific for AII. Thus, Peak A appears to represent a stable complex of AII with macrophage membrane structures that provide an immunologically relevant form of the antigen. These results are discussed with respect to a pathway for macrophage processing of peptide antigens to form a stable membrane-bound complex that is important for T cell responses.

Amino Acid Sequence↗
PubMed1984

Relationships between weight change and changes in blood pressure and serum lipids in men and women.

An examination was made of the relationships between weight change and changes in blood pressure and serum lipids over a five-year period in apparently healthy men and women not engaging in a systematic regime of diet and/or weight control. Weight change was positively correlated with systolic and diastolic blood pressure, cholesterol, and triglycerides, though the correlation coefficients were small (0.11 to 0.28) and not statistically significant for systolic blood pressure and cholesterol for men, and triglycerides for women. After controlling for the effects of differences in age, weight, physical work capacity and initial values in risk factors, and for changes in physical work capacity, weight change in women was found to account independently for a proportion of the variance of changes in systolic blood pressure (3 per cent), diastolic blood pressure (6 per cent), and cholesterol (2 per cent); in men weight change was independently related only to change in diastolic blood pressure (4 per cent). Subjects with elevated blood pressure (diastolic greater than or equal to 95 mmHg) were apparently more sensitive to weight change than those with 'normal' blood pressure. It was concluded that in free-living populations the relationships between weight change and changes in blood pressure and lipids are not strong, and that the general value of weight control in this context may have been exaggerated.

Adult↗
PubMed1983

Necrotizing enterocolitis in the asphyxiated full-term infant.

Five full term infants with necrotizing enterocolitis, confirmed histologically, presented in the first five days of life. All passed grossly bloody stools and three mucosal casts. Severe perinatal asphyxia with accompanying secondary hyperammonemia was present in all, and abnormal liver function studies were present in three. An awareness of the clinical characteristics of these infants may lead to their early identification and conservative management.

Ammonia↗
PubMed1983

Fecal alpha 1-antitrypsin excretion in young people with Crohn's disease.

Fecal alpha 1-antitrypsin excretion, a noninvasive indicator of protein-losing enteropathy, was correlated with clinical disease activity in pediatric patients with Crohn's disease. Disease activity was defined as the sum of 11 abnormal clinical parameters which were adapted from previously published disease activity scoring methods. Each patient was also given a subjective clinical rating when evaluated. In addition, four different devised disease activity scoring methods were correlated retrospectively with subjective clinical ratings for hospitalized patients. A total of 125 random fecal alpha 1-antitrypsin determinations were performed on 22 patients. Ninety-six percent of clinically active episodes of Crohn's disease were associated with elevated fetal alpha 1-antitrypsin (p less than 0.001). The degree of elevation was found not to correlate directly with the severity of assessed disease activity or site of intestinal involvement. A direct linear relationship was demonstrated between 23 paired random fecal alpha 1-antitrypsin and intestinal alpha 1-antitrypsin clearance assays (r = 0.93). There was a high, and remarkably similar, degree of correlation with each of the four different derived activity scoring methods and simple subjective ratings (r = 0.89-0.93). We conclude that: (a) fecal alpha 1-antitrypsin excretion may be helpful in assessing the presence or absence of Crohn's disease activity by providing an objective and specific indicator of intestinal damage; and (b) it appears that a simple subjective rating score is as clinically useful as other previously devised activity indices.

Adolescent↗
PubMed1983

Dose levels outside radiotherapy beams.

The specification of a radiotherapy generator calls for the leakage radiation through the housing of the source to be 0.1% (the ICRP has recently (1982) changed this figure to 0.2% of the dose rate inside the useful beam). When a patient is irradiated, the dose level outside the useful beam is not only determined by this leakage radiation, but also by scattered radiation from the beam-defining system and from the treatment volume of the patient. Measurements have been made on a 300 kV X-ray unit, and on two different 4 MV and one 8 MV linear accelerators to determine the levels of leakage radiation and scattered radiation in air, and in a phantom comparable in size to the trunk of the patient. Similar measurements have also been made for a 15 MeV neutron generator. It is shown that for all these generators the dose delivered outside the radiation beam is determined mainly by the two scattering processes mentioned, and it is argued that for linear accelerators it would be feasible to increase the permitted level of leakage radiation by a factor of 2 or 3 without a significant increase in the stray radiation delivered to the patient.

Humans↗
PubMed1983

Proliferating and helper T lymphocytes display distinct fine specificities in response to human fibrinopeptide B.

The fine specificity of T cell responses involved in the generation of help for antibody production and proliferation was examined by using the 14 amino acid peptide human fibrinopeptide B (hFPB, B beta 1-14) and its synthetic peptide homologues B beta 1-14(Lys14), B beta 1-13, and B beta 3-14. Peritoneal exudate or lymph node T cells from C57BL/10 and B10.BR mice immunized with hFPB or its synthetic homologues were used to measure in vitro proliferative responses. T cells from hFPB-immunized B10.BR mice showed specific proliferation to hFPB, but were unresponsive to B beta 1-14(Lys14), B beta 1-13, and B beta 3-14. B10.BR mice immunized with B beta 1-14(Lys14), B beta 1-13, or B beta 3-14 were unresponsive to all peptides tested. T cells from C57BL/10 mice showed no specific proliferation after immunization and challenge with any of the peptide antigens. In contrast to the patterns of T cell proliferation, immunization of both B10.BR and C57BL/10 mice with hFPB, B beta 1-14(Lys14), B beta 1-13, or B beta 3-14 primed for significant helper T cell activity, as assessed by the augmentation of a primary in vitro B cell IgM anti-FITC plaque-forming cell response after culture with B beta 1-1(Lys14)-FITC. Significant peptide-specific helper activity was observed when the FITC moiety was conjugated to the carboxyl terminal lysine (B beta 1-14(Lys14)-FITC) as well as FITC substitution at the amino terminus (FITC-B beta 3-13 or FITC-B beta 3-14). These results suggest that the fine specificity of T cell responses to peptide antigens are different for helper and proliferating T cells and that responsiveness by one T cell subpopulation does not predict the response pattern of other functional subpopulations.

Animals↗
PubMed1983

Functional differentiation in the genetic control of murine T lymphocyte responses to human fibrinopeptide B.

The ability to generate proliferative and helper T lymphocyte responses in mice was compared by using the 14 amino acid peptide, human fibrinopeptide B (hFPB). Lymph node or peritoneal exudate T cells from mice immunized with hFPB were assessed for in vitro proliferation to soluble hFPB as determined by the uptake of 3H-thymidine. The T cell proliferative response to hFPB was found to be under MHC-linked Ir gene control; mice possessing the H-2a,k haplotypes were responders, whereas H-2b,d,q,s mice were nonresponders. The influence of non-H-2 genes on these responses was not investigated, so exclusive regulation by H-2 is provisional. The absence of a detectable lymph node and peritoneal exudate T cell proliferative response persisted in H-2b,d,q,s mice after immunization and boosting with several doses of hFPB. In addition, the capacity to produce a T cell proliferative response was inherited in an autosomal dominant manner and gene(s) controlling responsiveness to hFPB mapped to the I-A subregion of the H-2 complex. To measure peptide-specific helper T cell activity, an in vitro microculture assay in which hFPB-primed lymph node T cells and normal spleen B cells and macrophages were used was developed measuring anti-fluorescein isothiocyanate (FITC) IgM and IgG plaque-forming cell (PFC) responses after culture with FITC-conjugated peptide. Immunization of B10.BR, C57BL/10, B10.D2, and B6AF mice with hFPB primed for significant helper T cell activity as assessed by the ability to augment a primary in vitro IgM response to FITC. The normal B cell IgM responses were completely dependent on hFPB-primed T cells and required that hapten (FITC) and carrier (peptide) be linked. In addition, immunization with FITC-conjugated peptide elicited positive in vivo PFC responses to FITC in B10.BR and C57BL/10 mice, indicating similar genetic control of helper activity in both the intact animals and the in vitro microcultures. Thus, B10.BR mice show both T help and T proliferative responses to hFPB, whereas C57BL/10 mice show only T help and no T proliferative responses. In contrast to B10.BR mice, C3H and CBA mice immunized with hFPB were completely unresponsive when assayed for helper T cell activity in vitro despite their ability to generate positive lymph node T cell proliferative responses. These results indicate responsiveness to hFPB by T helper and proliferating cells is different and is under separate genetic control.

Animals↗
PubMed1983

Thymocyte and macrophage interactions: separation of murine thymocyte subsets and enrichment of syngeneic cell-responding thymocytes by adsorption to macrophage monolayers.

The spontaneous binding of murine thymocytes to macrophage monolayers was employed to separate thymocytes into macrophage-unbound and -bound subsets, and the functional reactivities of these two subpopulations were examined. Macrophage-unbound thymocytes were found to be enriched in functional subsets reactive to semi-allogeneic and allogeneic stimulating spleen cells by proliferation in mixed leukocyte culture (MLC). Furthermore, macrophage-unbound thymocytes were frequently found to respond to syngeneic spleen cells. This syngeneic proliferative response showed both memory and specificity upon subsequent restimulation and thus seems to represent a syngeneic mixed leukocyte reaction (SMLR). Syngeneic responding thymocytes were also found to produce interleukin 2 when cultured with syngeneic but not allogeneic stimulator cells. In contrast, macrophage-bound thymocytes showed greatly reduced proliferative responses to allogeneic stimulators and no responses to syngeneic stimulators. The macrophage-bound thymocyte subset was not enriched in detectable suppressive activity; proliferative responses of macrophage-unbound thymocytes to either allogeneic or syngeneic cells were neither suppressed nor enhanced when macrophage-unbound thymocytes were added to the cultures. Thus, the macrophage-unbound subset seems to be enriched in functionally mature thymocytes and the macrophage-bound subset appears to be enriched in functionally immature thymocytes. This functional separation of thymocytes by macrophage adherence also correlated well with thymocyte subpopulations separated by bovine serum albumin density gradients; the low density mature thymocytes showed enhanced responses to both allogeneic and syngeneic stimulators, whereas the high density immature cells were unresponsive. This correlation was supported further by binding studies in which T cell tumor lines derived from C57BL/6 mice were used. ERLD tumor cells, which are similar to cortical immature thymocytes in both enzymatic and surface antigenic markers, were found to bind readily to macrophages, whereas both EL-4 and E male G2 tumor cells, with characteristics of mature thymocytes, bound to macrophages poorly. The binding of thymocytes and ERLD tumor cells to macrophages was not genetically restricted. We speculate that thymocyte binding to macrophages may play a critical role during the functional maturation of thymocytes.

Animals↗