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Biomedical subjects

R Lorentzon

Publications and source records attributed to R Lorentzon.

At least 109 records · Page 6Linked to original sources

Structure of the parathyroid glands, as revealed by different methods of fixation. A quantitative light- and electron-microscopic study in untreated Mongolian gerbils.

Stereology and semi-automatic image analysis were used with the aim of comparing the structure of parathyroid glands from untreated adult Mongolian gerbils fixed by immersion with those fixed by perfusion. Subclassification of the chief cells based upon the staining affinity or electron density of the cytoplasm was readily performed only in glands fixed by immersion, and so-called atrophic cells were observed only in these glands. The atrophic cells were often surrounded by "light" chief cells. In glands fixed by perfusion, "light" chief cells were only rarely encountered. A significant difference between glands fixed by immersion and those fixed by perfusion was found only with regard to the form of cells and nuclei, those fixed by perfusion being more spherical. When comparing individual cells within glands fixed by immersion, "light" chief cells were more spherical and had a significantly larger nuclear and cellular size, and a lower mitochondrial volume density than the "intermediate"/"dark" chief cells. Otherwise there were no significant differences in any of the parameters investigated. These data indicate that occurrence of so-called "light" chief cells and atrophic cells is a result of improper fixation. The results of this study do not favour the concept of a functional cycle with a simultaneous occurrence of active and inactive cells within parathyroid glands.

Animals↗

The normal parathyroid glands of the Mongolian gerbil. A quantitative structural study.

The parathyroid glands of the normal Mongolian gerbil were studied by light and electron microscopy, using stereology and semi-automatic image analysis. Basic quantitative data are presented for various nuclear parameters, and for mitochondria, endoplasmic reticulum, Golgi complex, secretory granules, storage granules, lysosomes and lipoid bodies. Chief cells predominate in the normal gland. Atrophic cells are only rarely encountered. The chief cells can be qualitatively subclassified into light, dark and intermediate variants, but quantitatively there is no difference among these variants with regard to the volume densities of mitochondria, lamellar rough endoplasmic reticulum, Golgi complex, secretory granules and storage granules, suggesting that the subclassification of the chief cells plays no functional role. A statistically significant correlation between volume densities of Golgi complex and secretory granules was found. Compared with the chief cells, the atrophic cells exhibit significantly less lamellar rough endoplasmic reticulum and secretory granules, whereas the content of vesicular rough endoplasmic reticulum is increased. The atrophic cells are suggested to be a degenerative variant of the chief cells.

Animals↗

Quantitative parathyroid morphology is unaltered in prolonged hypocalcemia. A quantitative electron microscopic study in the Mongolian gerbil.

Hypocalcemia was induced in adult Mongolian gerbils by a combination of a calcium deficient diet and repeated injections of ethylene-diamine-tetra-acetate (EDTA). This treatment caused tetany and death in some of the animals. Laboratory analyses on the eight experimental day disclosed significantly decreased concentrations of serum calcium and significantly increased concentrations of serum phosphate. Stereological methods and semi-automatic image analysis were used for ultrastructural study of the parathyroid glands with the aim of disclosing if any quantitative alterations occur in prolonged hypocalcemia. Compared with normocalcemic animals no significant change was observed in the hypocalcemic gerbils with regard to the nuclear profile area, the volume densities of nucleus, mitochondria, endoplasmic reticulum, Golgi complex, lysosomes, secretory granules and storage granules, or the surface density of the cell membrane. The only significant change in the hypocalcemic animals was a slight increase in the volume density of lipoid bodies and a similarly slight decrease in the surface density of the endoplasmic reticulum, changes which at present are difficult to explain. The data demonstrate that hypocalcemic stimulation in vivo does not give rise to quantitative morphological changes in parathyroid chief cells, and thus do not support the idea of a functional adaptation of the chief cells to variations in the ambient calcium concentration.

Animals↗

Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition.

Insulin is an important growth factor in man and mammals. In the present investigation, we have studied the incorporation of (35S)-sulfate into growth plate proteoglycans in normal, diabetic, insulin-treated diabetic, and marasmic rats. We found that diabetes leads to an all-but-total stop in the synthesis of sulfated glycosaminoglycans. The glycosaminoglycan chains actually synthesized were shorter than in normal rats. The proteoglycan monomers were smaller and did not form large aggregates in vitro. Marasmic rats and insulin-treated diabetic rats were intermediate between normal and diabetic rats with respect to sulfate uptake by cartilage, incorporation of cartilage sulfate into glycosaminoglycans, and the chain length of glycosaminoglycans. We conclude that insulin and nutrition play important but different roles in the biosynthesis of growth plate proteoglycans and thus for the longitudinal growth of skeletal bones.

Animals↗

Uptake of labeled alloxan in mouse organs and mitochondria in vivo and in vitro.

[14C]2-Alloxan was administered in vivo and in vitro for study of the uptake of alloxan in different organs and their mitochondia of mice. After in vivo administration, radioactivity was demonstrated in all organs investigated, with quantitative differences: endocrine pancreas greater than liver greater than exocrine pancreas and heart. No significant difference was found between the iv and ip routes of injection. An in vivo uptake of alloxan was also found in mitochondria, with significant quantitative differences as to the origin of the organelles: endocrine pancreas greater than liver greater than exocrine pancreas and heart. Pretreatment with D-glucose caused significantly decreased uptake in liver, exocrine pancreas, and heart, but significantly increased uptake in endocrine pancreas, whereas the uptake was significantly decreased in the mitochondria from all of these organs. In vitro uptake was observed in all kinds of mitochondria studied. This uptake was higher than the in vivo uptake in mitochondria from liver, exocrine pancreas, and heart, whereas the uptake in vivo was higher than the in vitro uptake in islet mitochondria. The presence of D-glucose did not affect the in vitro uptake of alloxan in mitochondria. The findings show that in vivo, alloxan passes across plasma membranes and is taken up by mitochondria, and data obtained with mitochondrial subfractions may also indicate a passage across mitochondrial membranes. D-Glucose protection against alloxan diabetogenicity may be associated with prevention of mitochondrial uptake of alloxan. This prevention seems to be dependent on the metabolism of glucose.

Alloxan↗

Intestinal absorption and 25-hydroxylation of vitamin D in patients with primary biliary cirrhosis.

The absorption, metabolism, and excretion of vitamin D3 was studied in eight women with an established diagnosis of primary biliary cirrhosis (PBC), and the results were compared with those obtained from eight healthy women of a similar age. Four patients had hyperbilirubinemia, low serum calcium levels, and a reduced mineral content of the bone, whereas the other four were presymptomatic with respect to bone disease. Vitamin D absorption was studied after oral administration of tritiated vitamin D, and the appearance of serum radioactivity was recorded. After this, the liver 25-hydroxylation of vitamin D was studied by administering an intravenous dose of tritiated vitamin D and then chromatographing serum samples to determine the radioactivity of the 25-OH D fraction. All PBC patients had normal 25-hydroxylation capacity of the vitamin, and there was no difference in the urinary excretion of radioactivity. On the other hand, the intestinal absorption of vitamin D was severely impaired both in the symptomatic and asymptomatic patients. The absorption of the vitamin was negatively correlated to the amount of fecal fat, and the results suggest that low serum levels of 25-OH D in symptomatic PBC seem to be caused by the steatorrhea, whereas hepatic conversion of vitamin D into 25-OH D seems to be well preserved even in patients with hyperbilirubinemia and signs of osteomalacia. The absorption-metabolism test may be a valuable tool in the study of patients with cholestatic liver disease for determining the nature of the vitamin D deficiency and the logical form of substitution therapy.

Adult↗

Normal hepatic vitamin-D metabolism in icteric primary biliary cirrhosis associated with pronounced vitamin-D deficiency symptoms.

The intestinal absorption and hepatic metabolism of vitamin D were studied in a woman with icteric primary biliary cirrhosis (PBC) complicated by pronounced bone pain and muscle weakness due to vitamin-D deficiency. The patient had a markedly reduced intestinal absorption of vitamin D, while the 25-hydroxylation of this vitamin was found to be normal despite the presence of longstanding icterus. The malabsorption of fat-soluble compounds secondary to the cholestasis was probably further impaired by several years of cholestyramine treatment. Administration of 1.25-(OH)2D3 increased intestinal calcium absorption, normalized serum calcium and increased bone mineral content of the proximal tibia. Furthermore, drastic improvement of muscle weakness and relief of bone pain were observed. It is recommended that repeated measurements of serum 25-(OH)D should be carried out in patients with PBC, and especially in those treated with cholestyramine. In certain vitamin D deficient patients, studies using radio-labelled vitamin D may provide clinically valuable information as to the exact site of the underlying disturbances.

Cholestyramine Resin↗

The prognosis in osteosarcoma.

Multifactorial analysis of patients with osteosarcoma of the distal femur and proximal tibia, recorded in the Swedish Cancer Registry during 1958 through 1968, disclosed a 5-year survival of 15.1% for femoral osteosarcomas and 38.1% for tibial tumours. The prognosis was better in adults than in children and better in males than in females. Tumour size, soft tissue involvement, the presence of pathological fracture and the duration of symptoms before treatment influenced the prognosis. The best treatment for the tibial lesions was high amputation alone, whilst for the femoral tumours primary ablative surgery was not superior to combined high-dose radiotherapy and delayed amputation. The main cause for the higher survival rate for tibial neoplasms seemed to be the fact that they were less advanced on admission than those of the distal femur. The findings emphasize the importance of early diagnosis and treatment for improved survival.

Adolescent↗

Immunotherapy with irradiated tumour cells and BCG in experimental osteosarcoma.

The effects of immunotherapy with irradiated tumour cells and BCG were studied in non-metastasizing variety of the Dunn osteosarcoma transplantable in mice. Experimental animals which had been preimmunized with three injections of 0.7 to 1.4 X 10(6) irradiated tumour cells each 1 to 3 weeks before administration of 1 X 10(6) living tumour cells, showed a tumour incidence of 23 per cent. This was significantly (P less than 0.005) lower than the 92 per cent tumour incidence in the control animals. Non-specific immunotherapy with BCG given subcutaneously at a dose of 1.0 mg of dry-weight bacterial mass three times at 3-week intervals was found to have no protective effect against the osteosarcoma. The tumour incidence was 90 per cent for BCG-treated and 94 per cent for control animals. The osteosarcomas were studied light and electron microscopically and also with regard to the histochemical alkaline phosphatase activity. No structural difference was found between the tumours of the various groups. The demonstrated immunotherapeutic response is in contrast to the low degree of immunogenicity of the osteosarcoma, which we will report elsewhere.

Alkaline Phosphatase↗

Serum calcium and phosphate concentrations and parathyroid morphology in rats treated with vitamin D metabolites.

The serum concentrations of calcium and phosphate and parathyroid morphology were studied in rats treated with vitamin D metabolites. Twenty hours after a single injection of 1.25-dihydroxycholecalciferol (1.25-DHCC) or 25-hydroxycholecalciferol (25-HCC) the serum calcium and phosphate concentrations were not significantly altered in any group, but the 1.25-DHCC treated rats exhibited an increased number of dark chief cells and occurrence of a few atrophic chief cells. Four to eight weeks after daily injections of the vitamin D metabolites the 1.25-DHCC treated rats exhibited significantly increased serum calcium concentrations and parathyroid glands composed of atrophic and dark chief cells in solid and follicular arrangement, whereas the rats treated with 25-HCC showed unaffected serum calcium concentrations and parathyroid glands composed of solid sheets of light chief cells, often with vacuolated cytoplasm, a few dark chief cells, but no atrophic cells. The findings suggest a direct or indirect suppressive influence of 1.25-DHCC on parathyroid activity in rats.

Animals↗

Quantitative data on the secretory granules in the normal mouse endocrine panreas. A morphometrical study using semi-automatic image analysis.

In order to obtain basic information on different morphometrical parameters a semi-automatic image-analysis of the secretory granules of the B-, A-, D- and PP-cells of the normal adult mouse endocrine pancreas was carried out. The following results were obtained: Cross sectional area of whole secretory granules: A greater than B greater than D greater than PP; cross sectional area of secretory granule cores: A greater than B; ratio of cross sectional area of whole secretory granules to secretory granule cores: 2.35 for B-cells and 1.74 for A-cells; maximum diameter of whole secretory granules: A greater than B greater than D greater than PP; maximum diameter of secretory granule cores A greater than B; form factor for whole secretory granules: A greater than B greater than D and PP; form factor for secretory granule cores: A greater than B. The findings show that the secretory granules of the parenchymal cells of the normal adult mouse endocrine pancreas differ from each other with respect to the size and form of both whole granules and cores.

Animals↗

Parosteal (juxtacortical) osteosarcoma. A clinical and histopathological study of 11 cases and a review of the literature.

At re-examination of all osteosarcomata recorded in the Swedish Cancer Registry during the years 1958 to 1968, 11 cases of parosteal osteosarcoma were found. No case of so-called periosteal osteosarcoma was identified. The tumours constituted 1.6 per cent of all proved primary malignant bone tumours. The ages of the 11 patients (six women and five men) ranged from 17 to 62 years (average 33 years). The clinical and histopathological findings of this study and of those collected from a review of the literature suggest the occurrence of two different types of parosteal osteosarcoma: the predominant type is originally benign but has a definite malignant potential, causing metastases after long symptom-free intervals; the other type is highly malignant from the beginning. Primary amputation is recommended for the latter category of tumours, and compartmental, radical en bloc resection followed by regular review is recommended for the former.

Adolescent↗

Study of the early blood glucose response of mice to alloxan.

The initial hyperglycemia in alloxan-treated mice was decreased by adrenalectomy and hypophysectomy, and abolished by occlusion of the hepatic blood flow for 5 min. or treatment with insulin after alloxan injection. No effect on the initial hyperglycemic response to alloxan was found in mice pretreated with phentolamine, or in those given alloxan after sham operation or after removal of ligatures for temporary occlusion of hepatic artery and portal vein. The concentrations of serum insulin and liver glycogen were decreased one and four hours after alloxan injection. The initial hyperglycemia is believed to be due to inhibition of insulin secretion by the B-cells and to the mobilization of glycogen from the liver. Pituitary and adrenocortical activity may contribute to this hyperglycemia. The origin of the hypoglycemic phase does not seem to be pancreatic, but may be hepatic.

Adrenalectomy↗

Growth rate of giant-cell tumor of bone: radiographic and clinical considerations.

The progression of giant-cell tumor of bone was studied in 2 patients, a 16-year-old girl and a 26-year-old man with abnormalities of the cancellous bone in the distal femur. The tumors had been overlooked in the first roentgenographic examination, and the patients were discharged without treatment. In the girl, the tumor grew from 33 cm3 to 85 cm3 in 65 days, and in the man from 11 cm3 to 175 cm3 in 311 days before the lesions were diagnosed. The high rate of growth of these neoplasms reflects the inherent malignancy of giant-cell tumors around the knee.

Adolescent↗

Stereological study of B-cell mitochondria in alloxan-treated mice.

Using stereological techniques, including semi-automatic image analysis, the B-cell mitochondria were studied in the pancreatic islets from one group of control mice and two groups of mice killed 10 min and 60 min, respectively, after alloxan administration. Ten min following alloxan the mitochondrial volume and envelope surface densities, the mean mitochondrial volume and surface area, and the area of mitochondrial profiles were significantly increased, whereas the mitochondrial numerical density was not significantly altered. At the 60 min observation time the mitochondrial volume density, the mean mitochondrial volume and surface areas, and the area of mitochondrial profiles were significantly decreased, whereas the mitochondrial envelope surface was not significantly altered. The findings indicate a rapid swelling, followed by disintegration of the mitochondria in the B-cells of alloxan-treated mice, thereby supporting our view that mitochondrial lesions play a primary role in the development of alloxan diabetes. These lesions are believed to be due to ionic alterations in the B-cells ("Pi-pH hypothesis").

Alloxan↗

Stereological study of endoplasmic reticulum, Golgi complex and secretory granules in the B-cells of normal and alloxan-treated mice.

Different B-cell organelles (lamellar and vesicular endoplasmic reticulum, Golgi complex, whole secretory granules and secretory granule cores) were studied stereologically in pancreatic islets from control mice and mice killed 10 or 60 min following alloxan injection. Ten min following alloxan a significant decrease was observed in the volume, surface and numerical densities of whole secretory granules and their cores, and a significant increase was found in the volume and surface densities of vesicular endoplasmic reticulum. At the 60 min observation time, a significant decrease was seen in the volume density of lamellar endoplasmic reticulum and Golgi complex, and in the volume, surface and numerical densities of whole secretory granules and their cores, and a significant increase was observed in the volume and surface densities of vesicular endoplasmic reticulum, and in the mean values for volume and surface of whole secretory granules and their cores. The stereological data indicate swelling of endoplasmic reticulum, decreased Golgi area, and decreased number and total volume and surface of secretory granules during the first hour after alloxan administration to mice. The observations may be consistent with inhibited insulin synthesis.

Alloxan↗

Extra-osseous osteosarcoma: a clinical and histopathological study of four cases.

Four cases of extra-osseous osteosarcoma were found among 242 cases recorded as osteosarcoma in the Swedish Cancer Registry during the years 1958 to 1968. The tumours occurred in middle-aged and elderly patients. Three of the tumours were situated in the proximal part of the thigh and one in the scapular region. Histopathologically, all tumours were subclassified as osteoblastic osteosarcomas. The patients were treated by primary local excision which in one case was followed by a radical en bloc excision of the entire tumour bed. All cases subjected to simple excision died of metastatic disease five to twenty-four months after diagnosis. The patient treated by en bloc excision is alive and apparently free from disease fourteen years after diagnosis.

Adult↗