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Biomedical subjects

F R Singer

Publications and source records attributed to F R Singer.

At least 127 records · Page 7Linked to original sources
PubMed1977

Microfollicular thyroid carcinoma with amyloid rich stroma, resembling the medullary carcinoma of the thyroid (MCT).

A human thyroid tumor is described which, on light microscopy, exhibited the features of medullary carcinoma of the thyroid (MCT). The cells were arranged in solid lobules or trabeculae, and the stroma was abundant and gave positive reaction for amyloid as assessed by congo red, crystal violet and thioflavin T stains. However, there was microfollicular differentiation in certain portions of the tumor even where the tumor was invasively growing. On electron microscopy, numerous microfollicles were identified even where unsuspected by light microscopy. There were junctional complexes, the cells possessed well developed rough endoplasmic reticulum, prominent Golgi and numerous dense bodies obviously derived from the Golgi vesicles, which were of the same morphology as "secretory" granules described previously by some authors in MCT. However, we find this kind of cytology typically in microfollicular thyroid carcinomas. Presence of about 100 A thick fibrils in the stroma was consistent with histochemically positive amyloid. The biochemical data were compatible with the differentiated follicular cell origin of the tissue. The homogenate contained poorly iodinated thyroglobulin, and thyroid peroxidase activity. Calcitonin was undetectable by a sensitive radioimmunoassay. It is concluded that this tumor was follicular thyroid carcinoma with amyloid rich stroma. The presence of amyloid and dense bodies with homogenous electron dense contents is insufficient for making conclusions about histogenesis of thyroid tumors. The so called MCT with amyloid stroma probably represents a heterogenous group of thyroid tumors, at least some of them derived from follicular epithelium.

Adenocarcinoma↗
PubMed1977

Evaluation of 99mTc diphosphonate kinetics and bone scans in patients with Paget's disease before and after calcitonin treatment.

Eleven patients with Paget's disease of bone underwent serial total body bone scars before and after therapy with calcitonin. All patients studied showed improvement clinically as well as biochemically. Scan improvement was noted in patients with mild disease. Patients with severe disease showed either to change or only slight improvement on the serial bone scars The scan was of greatest value in determining the extent of disease, especially in 3 patients in whom biochemical values were normal. A single pulse injection of 50 M.R.C. units of salmon calcitonin produced a significant increase in the blood clearance of 99mTc diphosphonate. The mechanism of this effect is not clear from this study.

Bone and Bones↗
PubMed1977

Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation.

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.

Adolescent↗
PubMed1977

Comparison of serum calcitonin levels after a 1-minute calcium injection and after pentagastrin injection in the diagnosis of medullary thyroid carcinoma.

A 1-min calcium injection was compared with a pentagastrin injection as provocative measures in stimulating calcitonin secretion in 4 patients with medullary thyroid carcinoma. In all cases the calcium injection resulted in a greater rise in serum calcitonin concentration. The patients tolerated the calcium injection well. However, two patients experienced substernal pressure and dyspnea following the pentagastrin injection. It is concluded that a 1-min calcium injection is a safe, rapid and effective procedure in the diagnosis of medullary thyroid carcinoma.

Calcitonin↗
PubMed1977

Use of 1,25(OH)2-vitamin D3 to separate 'types' on renal osteodystrophy.

Patients with severe symptomatic renal osteodystrophy were treated with either 1,25(OH)2D3 or 1 alpha(OH)D3. In 39 instances, there was either reversal of symptoms and/or a marked fall in plasma alkaline phosphatase. Bone biopsies showed improvement of either osteomalacia or osteitis fibrosa, and serum iPTH often fell. In thirteen patients, no improvement occurred. In seven patients, bone biopsy disclosed osteomalacia, and serum iPTH was normal or only slightly elevated. Thus, there was a defect in mineralisation. apparently unrelated to the lack of 1,25(OH)2D3 and in the absence of evidence of phosphate depletion. The other 'treatment failure' group showed osteitis fibrosa on biopsy and iPTH levels were markedly elevated. They are presumed to have marked secondary hyperparathyroidism. These 'treatment failure' groups had higher pre-treatment levels of serum Ca and Mg than in those showing a favourable response; also, hypercalcaemia developed rapidly during 1,25(OH)2D3 treatment. Thus, 1,25(OH)2D3 is efficacious in treating symptomatic osteodystrophy in many uraemic patients, and in other patients, it may help identify bone disease of other, as yet unknown, pathogenesis.

Adolescent↗
PubMed1977

Hypercalcemia and hypocalcemia.

This report discusses the various aspects of the hypercalcemic and hypocalcemic disorders. We first describe the physicochemical state of serum calcium and the interpretation of a rise or a fall in total serum calcium. The various diseases associated with alterations in the concentration of serum calcium are presented. The clinical manifestations of the hypercalcemic and hypocalcemic disorders and their management are described.

Acute Kidney Injury↗
PubMed1977

The etiology of Paget's disease of bone.

The etiology of Paget's disease is not known but recent studies of the ultrastructure of bone cells in pagetic lesions have raised the possibility of a viral etiology. In 41 of 41 patients evaluated in France and Los Angeles characteristic nuclear inclusions were found in osteoclasts only. These structures were similar to nuclear inclusions found in the slow virus infection of the brain, subacute sclerosing panencephalitis. Definitive identification of a virus or viral antigens in pagetic lesions awaits future studies. Other possible etiologies of Paget's disease include an inborn error of connective tissue biosynthesis, a disorder of hormone secretion, a vascular disorder, an autoimmune state, and a neoplastic transformation of bone cells.

Bone Neoplasms↗
PubMed1977

Human calcitonin treatment of Paget's disease of bone.

Human calcitonin has proven to be an effective drug in the management of Paget's disease. Bone pain decreased in a high percentage of cases and biochemical indices improved in all but a few instances. Radiologic regression of the disease often was seen after several years of treatment. The drug has been uniformly effective when administered to patients who have develped resistance to porcine or salmon calcitonin due to circulating antibodies. The incidence of side effects, mainly facial flushing and nausea, was variable and uncommonly resulted in discontinuation of treatment. Further studies are required to establish the minimum effective dose.

Alkaline Phosphatase↗
PubMed1976

Nuclear inclusions in Paget's disease of bone.

The ultrastructure of bone cells was examined in biopsies from 18 patients with Paget's disease of bone and from 60 patients with a variety of other bone diseases. A characteristic nuclear inclusion was found in the osteoclasts of each patient with Paget's disease. The nuclear inclusion most closely resembles viral nucleocapsids of the measles type.

Biopsy↗
PubMed1976

Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency.

Hypocalcaemia is a well-recognized manifestation of magnesium deficiency. We have studied seventeen patients with this syndrome in an attempt to determine the pathogenesis of the hypocalcaemia. Mean initial serum calcium concentration was 5-6 mg/dl and mean initial serum magnesium concentration was 0-75 mg/dl. Serum immunoreactive parathyroid hormone (IPTH) was measured in sixteen patients in the untreated state. Despite severe hypocalcaemia, serum IPTH was either undetectable (less than 150 pg/ml) or normal (less than 550 pg/ml) in all but two patients. Serial measurements made during the initial 4 days of magnesium therapy in four patients showed an increase in serum IPTH within 24h, but a delayed increase in serum calcium, which required approximately 4 days to reach normal values. The effect of the rapid normalization of serum magnesium on serum IPTH and serum calcium concentration was studied in three patients. Within 1 min after 144-300 mg of elemental magnesium was administered i.v., serum IPTH had risen from undetectable to 3600 pg/ml and 1725 pg/ml in two patients and from 425 pg/ml to 937 pg/ml in the third. Serum calcium concentrations were unchanged after 30-60 min. These data provide evidence for impaired parathyroid gland function in most of the magnesium deficient patients. The rapidity with which serum IPTH rose in response to magnesium therapy indicates that this may reflect a defect in parathyroid hormone (PTH) secretion rather than its biosynthesis. The failure of serum calcium concentration to increase during the initial days of magnesium repletion, at a time when serum IPTH concentrations were normal or elevated, suggests end-organ resistance to PTH in these patients. The renal response to PTH was examined in two magnesium deficient patients by measurement of urinary cyclic AMP excretion following administration of parathyroid extract. In both patients there was a minimal increase in urinary cyclic AMP concentrations. In contrast, when the hepatic response to glucagon was tested on the same patients by measurement of plasma cyclic AMP concentrations following administration of glucagon, normal increases were observed. These results suggest that adenylate cyclase systems of various organs may be affected differentially by a state of magnesium deficiency. It is suggested that magnesium deficiency may result in defective cyclic AMP generation in the parathyroid glands and in the PTH target organs. This could be the principal mechanism operative in both impaired PTH secretion and end-organ resistance to PTH which together contribute to the development of hypocalcaemia.

Adult↗
PubMed1976

Acute effects of calcitonin on osteoclasts in man.

To determine the mechanism by which calcitonin acutely decreases bone resorption in man, salmon or human calcitonin was administered intravenously to five patients with Paget's disease of bone immediately after an iliac crest bone biopsy. After 30 min an adjacent bone biopsy was taken and both were evaluated by light and electron microscopy. The results indicated that calcitonin both decreases the number of osteoclasts and alters the ultrastructure of these cells. Thes acute effects of calcitonin on osteoclasts confirm findings in other species and provide evidence in man that calcitonin, at least in part, retards bone resorption by inhibiting osteoclastic activity.

Animals↗
PubMed1976

Sites of clearance of endogenous parathyroid hormone in the vitamin D-deficient dog.

The sites of clearance of endogenous parathyroid hormone (PTH) were studied in dogs who developed secondary hyperparathyroidism on a vitamin D-deficient diet. Simultaneous blood samples were obtained from the femoral artery, and the hepatic, renal, portal, and femoral veins. Radioimmunoassay of canine immunoreactive PTH (iPTH) in a heterologous bovine PTH (bPTH) system indicated that the kidney and liver extracted 49% and 46%, respectively, of the iPTH circulating through these organs. Characterization of the circulating iPTH in these animals was carried out by gel filtration and radioimmunoassay of the eluant fractions utilizing specific amino- and carboxyl-terminal antisera. The hormone in the peripheral circulation co-eluted with [125I]-iodobPTH and no fragments of iPTH were detected. Immunochemical differences between bovine and canine PTH were detected in the carboxyl-terminal region of the molecule. The results indicate that endogenous PTH in the vitamin D-deficient, hypocalcemic dog is cleared by the kidney and liver and that the predominant form of the hormone in this animal is similar to glandular bPTH 1-84.

Animals↗
PubMed1976

The high incidence of persistent secondary hyperparathyroidism after renal homotransplantation.

Sixty-eight patients were observed for a period of up to seven years after transplantation. Serum parathyroid hormone levels were measured in 41 patients; 17 patients had persistent hypercalcemia for a period of from one to seven years. Serum parathyroid hormone levels were elevated in seven of these 17 patients. Serum parathyroid hormone was elevated in 11 of the other 24 patients with normocalcemia. The function of the kidney was not affected either by the state of hypercalcemia or persistent hyperparathyroidism. Aseptic necrosis was significantly present in those of the hypercalcemic group. It is suggested that persistent hypercalcemia is an important precipitating, if not the main, cause of an aseptic necrotic condition of the bones.

Calcium↗
PubMed1975

Peripheral metabolism of bovine parathyroid hormone in the dog.

Four dogs were infused with highly purified bovine parathyroid hormone until constant levels of immunoreactive hormone were attained in the circulation. Simultaneous samples of plasma were then obtained from the aorta, from hepatic, renal, and femoral veins, and later from a pulmonary artery and the left ventricle. Radioimmunoassay of these samples revealed mean arteriovenous differences of -23% across the liver and -19% across the kidney. No significant differences were found across the lung or lower extremity. After termination of the infusion the disappearance rate of immunoreactive hormone in external jugular-venous blood was multiexponential: the predominant initial T 1/2 was 4, 6, and 8 min, and the terminal component was 60, 54, and 99 min. respectively, in 3 dogs.

Animals↗
PubMed1975

Release of calcitonin by cultures of medullary carcinoma of the thyroid.

Three biopsies of medullary carcinoma of the thyroid were grown in monolayer culture. All three cultures initially released high levels of calcitonin into the medium, but the conretion from the culture cells was not stimulated when the medium calcium concentration was increased from 1.8 to 3.6 mEq/L. Four peaks of calcitonin immunoreactivity were found when the culture medium of one cell line was fractionated by gel filtration on Bio-Gel P-10. This closely corresponded to the heterogeneous molecular profile of calcitonin in the serum of this patient and other patients with medullary carcinoma of the thyroid.

Calcitonin↗