Search PubMed⌕ Search

Biomedical subjects

M J Atkinson

Publications and source records attributed to M J Atkinson.

70 records · Page 4Linked to original sources
PubMed1984

Autoantibodies against parathyroid hormone in a patient with terminal renal insufficiency.

An autoantibody against mid-C-regional, possibly mid-regional, parathyroid hormone was detected in the plasma of a patient with terminal renal insufficiency who was on intermittent haemodialysis. 43-68(Tyr)hPTH and 42-55(Tyr)hPTH were selectively bound by his IgG fraction. 43-68(Tyr)hPTH had the highest affinity for the autoantibody; intact parathyroid hormone did not displace radiolabelled 42-55(Tyr)hPTH or 43-68(Tyr)hPTH. As concentrations of circulating antibodies against mid-C/mid-regional parathyroid hormone fell rises in intact and mid-C-regional parathyroid hormone levels and in alkaline phosphatase activity were observed. This autoantibody directed against the middle portion of the parathyroid hormone molecule seemed to have some protective properties against the osteoblast-stimulating activity of the hormone, implying that the mid-C-region or middle region of the molecule has some biological importance.

Adult↗
PubMed1984

Osteoporosis: a bone turnover defect resulting from an elevated parathyroid hormone concentration within the bone-marrow cavity?

Recently the bone-marrow cavity blood concentration of parathyroid hormone (PTH) has been shown to exceed that of the peripheral blood. As PTH is a primary modulator of bone cell activity, altered levels of the hormone in the bone-marrow blood may play a significant role in the aetiology of bone disease. We therefore measured PTH concentrations in marrow cavity and venous blood of 9 osteoporotic and 14 control subjects using sequence specific radioimmunoassays for intact and mid-carboxyl (Mid-C) regional human PTH (hPTH). Intact and Mid-C PTH levels were identical in the peripheral blood of control and osteoporotic subjects. Furthermore, bone-marrow cavity blood concentrations of Mid-C PTH, whilst universally higher than those found in peripheral blood, were also comparable in the osteoporotic and control subjects. The sole difference in the PTH composition of bone-marrow cavity blood from osteoporotic subjects was an increased concentration of intact PTH. The origins and consequences of elevated levels of intact PTH within the marrow cavity blood of osteoporotic subjects are discussed.

Bone Marrow↗
PubMed1984

Analysis of immunoreactive and biologically active human parathyroid hormone-peptides by high-performance-liquid-chromatography.

A combination of high-performance-liquid-chromatography (HPLC), sensitive radioimmunoassays and a homologous in vitro bioassay was used to characterise human parathyroid hormone (hPTH)-peptides in human parathyroid adenoma and plasma. Chromatography of several synthetic hPTH-peptides allows the calibration of the HPLC column. On the basis of sequence hydrophobicity the elution position of peptides can be predicted. A model for the determination of the minimal peptide sequence of each peptide has been developed which based on immunological and physico-chemical properties allows the characterisation of unknown hPTH-peptides. Using this technique the heterogeneity of circulating hPTH-peptides in human plasma has been examined. Plasma extracts from healthy individuals, osteoporotic, hyperparathyroid and pseudo-hyperparathyroid patients were investigated. A uniform pattern in the heterogeneity of hPTH-peptides was detected. Using parathyroid adenoma as reference disease specific changes were characterised.

Adenoma↗
PubMed1984

Some effects of parathyroidectomy on cell-mediated immune responses in the rat.

Xenografts of mouse tail skin to the rib cages of normal and sham-parathyroidectomized rats caused an increase in plasma calcium concentration and concomitant increase in bone marrow mitosis. Neither was elicited in aparathyroid rats and graft survival was prolonged in these animals. No hypercalcaemic episode was associated with the delayed hypersensitivity response induced by painting rat ears with oxazolone. Compared with the response in sham-parathyroidectomized rats, that in parathyroidectomized rats was enhanced although both responses were less than that in normal rats. Parathyroidectomy of parental donors did not affect the ability of their splenic lymphocytes to mount a graft-versus-host response in F1 hybrid recipients. When sham-operated and aparathyroid parents were sensitized with F1 hybrid lymphocytes no differences were observed in a subsequent graft-versus-host response in F1 recipients. However, when aparathyroid F1 recipients were employed a marked reduction in the graft-versus-host reaction was observed. Thus the clonal expansion of cells with specific reactivity to certain antigens in secondary lymphoid tissue, which is driven by those same specific antigens, is not affected or only moderately affected by the parathyroid status of the animal. However, the more general increase in lymphocyte numbers promoted by non-specific mitogenic lymphokines is markedly impaired in the hypocalcaemic parathyroidectomized rat. Furthermore, the parathyroid gland is essential for the development of a hypercalcaemic episode which follows antigenic challenge and causes cell proliferation in primary lymphoid tissues. This surge of mitosis could serve to replenish the depleted pools of virgin T and B lymphocytes in the secondary lymphoid tissue which occur as a result of their response to antigens.

Animals↗
PubMed1983

Parathyroid hormone concentration gradients across the human bone marrow.

Parathyroid hormone (PTH) concentrations were compared in blood drawn from the bone marrow and antecubital vein of patients undergoing marrow biopsy for suspected hematological neoplasia. Radioimmunological analysis revealed that the bone marrow blood had a higher PTH content than blood from the peripheral circulation. Thyroid hormone-binding globulin was not distributed asymmetrically, showing that the gradient is PTH specific. The intact PTH content of marrow blood was 65% greater than that in the venous system, whereas carboxyl regional PTH levels showed a 34% gradient in favor of the marrow. Although the majority of patients were found to have hematological malignancies, there was no discernible influence of tumor on the PTH gradients. The physiological implications and possible origins of the asymmetrical PTH distribution are discussed.

Bone Marrow↗
PubMed1983

Sodium and ouabain induce proliferation of rat thymic lymphocytes via calcium- and magnesium- dependent reactions.

When the concentrations of either calcium or of magnesium in the culture medium were increased from the normal 0.6 and 1.0 mM to 1.8 and 2.5 mM respectively mitotic activity of rat thymic lymphocytes increased. Very high (10(-4)M) ouabain concentrations abolished these mitogenic actions whilst lower (10(-7) and 10(-11)M) concentrations had no effect. However in the normal medium these lower concentrations of ouabain were themselves mitogenic. The stimulatory effect of 10(-7)M ouabain was calcium-dependent and oestradiol-blockable and that of 10(-11)M magnesium-dependent and testosterone-blockable. A 10 mM increment in extracellular sodium concentration also stimulated mitosis in these cells in a calcium-dependent manner whilst a 20 mM increment required the presence of magnesium to exert its mitogenic effect. However, when similar osmotic increments were provided by potassium and lithium salts, or sucrose no mitotic stimulation was provoked. Subtle interactions between sodium and the divalent cations are clearly involved in events which lead to mitosis and the steroids oestradiol and testosterone can somehow block these effects.

Animals↗
PubMed1983

A homologous biological probe for parathyroid hormone in human serum.

A method of measuring the biological activity of parathyroid hormone (PTH) in human serum that depends on the activation of its natural target enzyme, human renal cortical adenylate cyclase, is described. Optimal sensitivity ranging in different assays from 14 to 20 pg 1-34 hPTH/ml was achieved in the presence of the GTP-analogue GppNHp (10 mumol/L), 5 mmol/L MgCl2 and 1.25 mmol/L EGTA. Basal and stimulated cAMP production was reproducible within assays (c.v. below 7%, S.E.M., n = 3) and between assays (c.v. 5 to 14%, S.E.M., n = 4). The recovery of 1-34 hPTH added to individual test sera averaged 94%. The specificity of the method was established as follows: 1.) Other tested hormones, at 100 ng/ml, were ineffective; 2.) In the majority of peripheral sera from patients with hyperfunctioning parathyroid glands elevated bio-activity was detected; 3.) The circulating bio-activity fell rapidly after removal of parathyroid adenomata; 4.) Treatment with antisera for hPTH reduced the bio-activity; 5.) A PTH-antagonist inhibited the bio-activity.

Adenoma↗
PubMed1983

Hepatic osteodystrophy in primary biliary cirrhosis: a possible defect in Kupffer cell mediated cleavage of parathyroid hormone.

Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25-hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25-dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl-regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl-regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Influence of age, strain and season on diurnal periodicity of thyroid stimulating hormone, thyroxine, triiodothyronine and parathyroid hormone in the serum of male laboratory rats.

The influence of age, strain and season on the diurnal pattern of serum hormone levels from the pituitary-thyro-parathyroid complex was studied in male laboratory rats. Distinct 24 h periodicity in the serum levels of thyroid stimulating hormone (TSH) and triiodothyronine (T3) was observed in all groups of rats. There was no influence of age (40, 60 and 90 days old Sprague-Dawley rats), but a significant influence of strain (Sprague-Dawley vs. BH/Ztm rats) and season (summer vs. winter) on the diurnal pattern of serum TSH and T3 levels. Significant 24 h periodicity in serum thyroxine (T4) levels existed during winter in BH/Ztm rats, but not in Sprague-Dawley (SD) rats of any age. Adult SD rats demonstrated 24 h periodicity in serum levels of T4 only in summer. No diurnal periodicity in serum levels of parathyroid hormone (PTH) was observed in any group of rats. There were significant changes in 24 h mean serum levels of TSH and T3 throughout pubertal development. Twenty-four h mean serum levels of T3 and T4 were significantly higher in summer than in winter. Twenty-four h mean serum levels of T4 were significantly lower in BH/Ztm rats than in SD rats. Significant correlation was observed between serum concentrations of T3 and T4, TSH and T4, and between TSH and T3 in some groups of rats, but not in all. The results indicate that 24 h periodicity of serum hormone levels from the pituitary-thyroid complex of male laboratory rats may vary with age and strain of the animals and with the season of experiment performance.

Age Factors↗
PubMed1983

Circannual variations in serum concentrations of pituitary, thyroid, parathyroid, gonadal and adrenal hormones in male laboratory rats.

Seasonal effects were studied on basal levels of hormones in the serum of adult male Sprague-Dawley rats, which were born and raised under rigorously controlled laboratory conditions. Groups of 90-day-old rats were killed at monthly intervals by rapid decapitation. Significant fluctuations were observed throughout the observation period of 19 months in serum levels of TSH, prolactin, androgens, tri-iodothyronine and LH. Minor fluctuations were observed in serum levels of FSH, corticosterone, parathyroid hormone and thyroxine. The results indicate that male laboratory rats exhibit circannual and semi-annual fluctuations in serum levels of several hormones even though the animals were born, raised and maintained in constant laboratory conditions.

Androgens↗
PubMed1982

Characterisation of the binding sites of anti-parathyroid hormone antisera using synthetic parathyroid hormone peptides.

Four antisera raised against partly purified PTH preparations all showed a wide range of specificities when reacting with radioiodinated PTH peptides representing several different portions of the intact hormone sequence. In contrast, antisera raised against individual peptides were only able to cross-react with other peptides that contained all or part of their amino acid sequence in common. Cross-reacting peptides were seen to contain one or more amino acid residues having high interspecies variability in common. We have explained the antigenicity and cross-reactivity of the peptides on the basis of these common highly variable amino acid sequences. We have concluded that the selection of hormonal material in radioimmunoassays for PTH should be made on the basis of the highly variable amino acid residue content. This will allow a narrowing of the assay specificities and permit detection of a desired region of the PTH hormone.

Animals↗
PubMed1981

Changes in plasma levels of calcium and in bone marrow mitosis after antigenic challenge in rats and mice.

When rats or mice were immunized with sheep red blood cells, bacterial lipopolysaccharides or bovine serum albumin, a proliferative response could be detected in the bone marrow and spleen. This response was associated with a hypercalcaemic phase. Parathyroidectomy, which resulted in a protracted hypocalcaemia, prevented the development of an increase in levels of plasma calcium. This operation also prevented the rise in bone marrow proliferations following antigenic challenge, but did not ablate the normal proliferative response to antigen by cells in the spleen. Antibody production and numbers of antibody-forming cells were not significantly reduced by parathyroidectomy. These results suggest that there is a pool of antigen-insensitive cells in the bone marrow which are stimulated after antigenic challenge. It is postulated that these events were mediated by the development of a parathyroid-dependent hypercalcaemia which stimulates the cells non-specifically. These events may form part of a cellular homeostasis, replacing cells in peripheral lymphoid tissues.

Animals↗
PubMedDate not supplied

Homologous radioimmunoassay for human mid-regional parathyroid hormone.

A radioimmunoassay, selective for the clinically important mid region of human parathyroid hormone (hPTH), is reported. The synthetic 44-68 amino acid sequence (h44-68PTH) was used as both the standard and tracer material. This eliminated many of the undesirable characteristics associated with PTH assays the employ hormone of biological origin. These components allowed the detection of mid regional fragments present in both intact and fragmented hPTH, with a working range between 50 and 2500 pg/ml h44-68PTH. There was no interference from serum proteins and no significant cross reactivity to a range of N-terminal, C-terminal and other mid regional hPTH peptides. The assay proved to be rapid (total time 24 h) and was extremely reproducible, with an intraassay and interassay variation of 2.8% and 5.6% respectively (expressed as percentage SE in mean). The plasma concentration of normal subjects was established as 129 +/- 6 pg/ml (h44-68PTH) with a range of 50-300 pg/ml (n = 42). This assay, using fully synthetic hPTH peptides, was able to distinguish between euparathyroid and hyperparathyroid subjects, which suggests that the assay is of diagnostic value.

Amino Acid Sequence↗
PubMedDate not supplied

Computerized quality-of-life screening in an oncology clinic.

PURPOSE: The purpose of these studies was to assess the feasibility and reliability of computerized quality-of-life screening for patients attending an outpatient breast cancer clinic. The screening program involved a computerized administration of the European Organization for Research and Treatment of cancer QUality of Life Questionnaire (EORTC QLQ-C30). The computer software generated a screening report that clinic staff members used in the clinical encounter to assist in identifying quality-of-life problems. DESCRIPTION OF STUDY: Two studies are reported. In study I, 36 patients and either their nurses or physicians evaluated the feasibility of the screening program using questionnaires developed for this study. In study II, a separate sample of 50 patients completed both the computerized and paper-and-pencil versions of the QLQ-C30 to assess reliability and consistency of responding. RESULTS: The results of study I indicate that the patients found the computerized administration to be an acceptable means of providing staff members with information on day-to-day functioning. Clinic nurses and physicians indicated that the report was useful in identifying problematic quality-of-life domains. The results of study II indicate that the computerized administration is highly correlated with the paper-and-pencil version and has similar internal consistency. Discrepancies in responses were identified, but were at an acceptable level. CLINICAL IMPLICATIONS: The results of these studies indicate that computerized quality-of-life screening is feasible and may provide reliable data for research and quality assurance studies. Staff evaluations suggest that the written report may provide clinic staff members with a tool for identifying quality-of-life concerns in which individual patients are experiencing difficulty. Potential benefit to patients include productive use of waiting room time, greater efficiency in the assessment process, and an improved likelihood that nurses and physicians will recognize and attend to quality-of-life deficits. The valid, reliable, and efficient identification of important patient quality-of-life concerns allows multidisciplinary team members to focus meaningfully their clinical efforts within their respective areas of responsibility.

Adult↗