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Biomedical subjects

R Lorentzon

Publications and source records attributed to R Lorentzon.

At least 19 recordsLinked to original sources

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

Transplantable osteosarcoma in mice. Structural characterization of a transplantable osteosarcoma obtained in an allogenic system.

Light microscopic, histochemical and ultrastructural studies of a transplantable mouse osteosarcoma were carried out. The osteosarcoma grew in CBA mice after injection of cultured cells derived from a Dunn osteosarcoma. The tumour differed from the original Dunn osteosarcoma with respect to metastatic potential and structural features. The transplantable tumour was an anaplastic, richly vascularized fibroblastic osteosarcoma with alkaline phosphatase activity and rather sparse osteoid formation, resulting in death of the animals within 6 to 8 weeks. Virus particles were found intracellularly, mainly localized to cisterns of rough endoplasmic reticulum, and extracellularly often close to plasma membranes and collagen fibres. Sign suggestive of formation of collagen fibres by tumour cells were observed. A possible viral influence upon the tumour was suggested also by its growth behaviour in vitro. The results indicate that this new transplantable tumour, obtained in an allogenic system, represents a clonal derivative of the original Dunn osteosarcoma.

Animals

Influence of 1,25-dihydroxycholecalciferol on parathyroid activity in patients with primary hyperparathyroidism.

Parathyroid morphology and blood chemistry were studied in five patients with primary hyperparathyroidism treated with 1,25-dihydroxycholecalciferol (1,25-DHCC) for 2 to 11 days before planned operation. Before the institution of treatment all patients were hypercalcemic, whereas the serum immunoreactive parathyroid hormone (iPTH) concentration either was elevated or normal. During the treatment the urinary phosphate excretion was significantly increased, whereas the calcium excretion and the serum concentrations of calcium and phosphate were unaffected or only slightly changed. Serum iPTH decreased during the first days of treatment, but returned then to increased levels close to the pretreatment ones. The treatment was tolerated well by the patients. Light and electron microscopy of the removed parathyroid glands disclosed one adenoma in each of the five patients, the other glands exhibiting either a slight hyperplasia or a normal appearance. Both the adenomatous and the non-adenomatous parathyroid tissue showed a predominance of dark chief cells and three of the adenomas exhibited a varying number of atrophic and oxyphil cells. The non-adenomatous glands were composed of atrophic and dark chief cells. Signs of low functional activity were ultrastructurally observed in the parathyroid parenchymal cells. It is suggested that 1,25-DHCC treatment of patients with primary hyperparathyroidism inhibits parathyroid hormone secretion.

Adult

Structural changes in parathyroid glands exposed to vitamin D metabolites in vitro.

Isolated parathyroid glands from normal adult Mongolian gerbils were incubated for 10 minutes to 16 1/2 hours at high, medium or low concentrations of Ca2+, with or without added 1,25-dihydroxycholecalciferol (1.25-DHCC) or 25-hydroxycholecalciferol (25-HCC), after which they were studied electron microscopically. 1,25-DHCC appeared to potentiate the inhibitory action of high calcium on parathyroid activity, whereas 25-HCC had no structurally detectable effect.

Animals

Intestinal absorption and tissue retention of cadmium and calcium in normal adult rats and rats given an active metabolite of vitamin D (1,25-dihydroxycholecalciferol).

1. Nine-months-old male rats were divided into a normal control group and one experimental group which received eight daily intraperitoneal injections 15 pmol of 1,25-dihydroxycholecalciferol/100 g body weight. After 5 days, 20 muCi of 109CdCl2 or 20muCi of 45CaCl2 was administered by stomach tube. The intestinal absorption and tissue retention of the radioisotopes were analysed during the next 3 days, the animals being kept in metabolic cages. 2. The administration of 1,25-dihydroxycholecalciferol caused significantly increased net absorption of intestinal calcium, hypercalcaemia and increased incorporation of calcium into bone. In comparison, there was no significant effect on the intestinal absorption of trace doses of cadmium or upon the accumulation of cadmium in the liver and kidneys.

Animals

Osteosarcoma. A multifactorial clinical and histopathological study with special regard to therapy and survival.

A multifactorial analysis was performed on all 153 unequivocal cases of genuine osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968. Cases of so-called parosteal osteosarcoma, soft-tissue osteosarcoma and osteosarcoma secondary to Paget's disease of bone were not included. The osteosarcomas were subclassified as follows: osteoblastic (69 per cent), chondroblastic (19 per cent) and fibroblastic (12 per cent). The overall 5-year survival rate was 22 per cent; 55 per cent for those who had undergone amputation above the joint proximal to the involved skeletal part, 22 per cent for those amputated on the involved skeletal part, 11 per cent for those treated with local extirpation of the tumor, and 1 per cent in cases in which the lesion was not radically removed. Tumors of the femur, humerus and scapula were as malignant as axial tumors. The former carried a 5-year survival rate of 13 per cent, regardless of whether the patients had been treated with exarticulation or amputation on the involved skeletal part. Patients with axial tumors showed a 5-year survival rate of 15 per cent. These survival data suggest that proximal amputation alone might suffice for lesions situated distally to the knee and elbow joints, while tumors in the humerus and femur should be treated with amputation combined with multicytostatic treatment or immunotherapy and axial tumors with local resection and multicytostatic or immunologic treatment.

Adolescent

Telangiectatic osteosarcoma.

Of the 242 cases of osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968 only one was found to represent telangiectatic osteosarcoma. Another case was recently diagnosed in our department. The characteristic morphologic features of these neoplasms were anaplastic stroma, high mitotic activity, osteoid-formation, widely anastomosing blood spaces, and alkaline phosphatase activity. The experience gathered indicates that telangiectatic osteosarcoma constitutes a histopathologic variant of genuine osteosarcoma with a serious prognosis, necessitating the same kind of treatment as for the genuine tumour.

Adolescent

The influence of 1,25-dihydroxycholecalciferol on the ultrastructural organization of skeletal muscle fibres. Morphometric analyses on vitamin D deficient or calcium deficient growing rats.

Ultrastructural evidence was obtained from vitamin D deficient and calcium deficient rats that the sarcoplasmic reticulum (SR) is involved in the intracellular calcium transport of the muscle cell. In the absence of vitamin D there was a relative decrease in SR volume and a compensatory increase in mitochondrial volume. Administration of exogenous doses of 1,25-dihydroxycholecalciferol significantly increased SR volume, while mitochondrial volume correspondingly decreased. This supports the hypothesis that the production of calcium binding proteins within the SR is influenced by active metabolites of vitamin D.

Animals

Excretion of active metabolites of vitamin D in urine and bile of the adult rat.

1. One-year-old male rats were injected intravenously with 200 pmol of 25-hydroxy[26(27)-methyl-3H]cholecalciferol per 100 g body weight and the presence of this metabolite of vitamin D, as well as other metabolites, produced during the following 8 h was examined in serum, urine and bile. 2. The chromatography data indicated an excretion of 25-hydroxycholecalciferol both in bile and urine and, in urine, also of 1,25-dihydroxycholecalciferol. In bile, fractions of labelled substances were also obtained which, according to their elution positions, might represent cholecalciferol and conjugated metabolites. 3. The excretion of active metabolites of vitamin D in normal urine might be elevated in chronic renal failure and, in conjunction with a reduced synthesis, contribute to the occurrence of renal osteodystrophy.

Animals

Vitamin D metabolism in adult rats at low and normal calcium intake and the effect of cadmium exposure.

1. Chromatography measurements indicated that adult rats converted 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol at a lower rate than that reported earlier for young animals. In serum, less-polar metabolites were found which probably represented vitamin D esters and vitamin D3. 2. A low dietary intake of calcium resulted in an evident increase in the fraction corresponding to 1,25-dihydroxycholecalciferol in the kidneys and also in the intestinal mucosa and serum. 3. Inclusion of 0.67 mmol of cadmium/l of drinking water at a low dietary intake of calcium resulted in an increased accumulation of both cadmium and zinc in the kidneys and liver compared with values at a normal dietary calcium intake. 4. At a normal dietary calcium intake, cadmium exposure caused inhibited production of 1,25-dihydroxycholecalciferol by the kidneys and an increased accumulation of 24,25-dihydroxycholecalciferol, vitamin D3 and vitamin D esters in the serum. 5. The inhibitory effect of cadmium on the renal conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol was almost completely counteracted by a simultaneous low dietary calcium intake. Cadmium-exposed, calcium-deficient animals also showed a maintained accumulation of 1,25-dihydroxycholecalciferol in the intestinal mucosa.

Animals

The effect of immunotherapy with BCG on the development of radiostrontium (90Sr)-induced osteosarcoma.

The development of radiostrontium-induced osteosarcoma was studied in BCG-treated and in untreated control mice. Within the observation period of 420 days after the administration of radiostrontium there was a total tumour-incidence of 89.5 and 90.5 per cent for the respective groups of animals. There was no statistically significant difference between the two groups, neither with regard to the time of the first roentgenographic appearance of the osteosarcoma, nor concerning the total tumour incidence , nor with regard to the distribution of the primary sites of the tumours. The tumours of the BCG-treated animals showed a clear tendency to a slower growth rate in comparison to that of the tumours in the control animals. This effect was probably immunological in nature. The mortality in osteosarcoma following radiostrontium administration, however, showed no significant difference between the two groups. Light microscopical and ultrastructural examination did not disclose any clear structural difference between the tumours from BCG-treated and untreated control animals.

Animals

Angiography in giant-cell tumours of bone.

The angiographic appearance of 9 cases of genuine giant-cell tumour of bone, 6 cases of aneurysmal bone cyst and one case of non-ossifying fibroma is described. Differential diagnosis would appear to be possible to a certain extent. The non-ossifying fibroma was poorly vascularized. The genuine giant-cell tumours were hypervascularized as well as some of the aneurysmal bone cysts making a differential diagnosis in these cases impossible. On the other hand, a poorly vascularized tumour devoid of soft tissue component and arteriovenous fistulas is probably an aneurysmal bone cyst. A hypervascular soft tissue component is of great prognostic value in cases of geniune giant-cell tumour.

Angiography

The role of the parathyroids for the adaptation to a low calcium intake. 5. The long-term effect of parathyroidectomy on the adaptation to a low calcium intake in adult rats with special reference to the metabolism of vitamin D.

One-year-old selectively parathyroidectomized rats showed a normalization of their plasma calcium level to above 4.1 mEq/l in 38% within 18 weeks on a normal dietary intake of calcium and inorganic phosphate but low in vitamin D. On a low level of dietary calcium, normalization did not occur in any of the parathyroidectomized animals. The conversion of 25-hydroxycholecalciferol into the active metabolite of vitamin D, 1,25-dihydroxycholecalciferol, by the kidneys was stimulated by a low dietary intake of calcium in intact animals and the accumulation of this metabolite was increased in small intestine mucosa. This adaptory increase in the level of intestinal 1,25-dihydroxycholecalciferol was not disturbed by selective parathyroidectomy, nor the synthesis by the kidneys. The synthesis reached a limit above which no further increase occurred despite the prevailing hypocalcemia possibly through an influence of the concomitant hyperphosphatemia. The renal synthesis and intestinal accumulation of 1,25-dihydroxycholecalciferol were directly related to the intestinal net absorption of dietary calcium, which we have reported on previously. Although increased, the endogenous level of 1,25-dihydroxycholecalciferol was too low to accomplish mobilization of skeletal calcium necessary for adaptation to a low calcium intake, as we have reported elsewhere. Thus, for adaptation skeletal calcium reserves must become mobilized through stimulated parathyroid activity with resulting osteoporosis. The parathyroids were found to have no direct regulatory influence upon the synthesis of 1,25-dihydroxycholecalciferol.

Adaptation, Physiological

Low doses of 1,25-dihydroxycholecalciferol increase mature bone mass in adult normal rats.

Low doses of 1,25-DHCC cause a significant increase in trabecular and cortical bone mass of the mature rat skeleton by stimulated endosteal bone formation. The increased serum contents of calcium and inorganic phosphate give rise to a moderate nephrocalcinosis. An increased bone resorption occurs upon toxic dose levels causing profound nephrocalcinosis. Similar doses of 25-HCC do not affect the mature bone.

Animals

Fibrosarcoma of bone. A demographic, clinical and histopathological study of all cases recorded in the Swedish cancer registry from 1958 to 1968.

The clinical records, radiographs and histopathological material of all forty-one patients recorded as suffering from fibrosarcoma of bone in the Swedish Cancer Registry for the years 1958 to 1968 have been analysed; in addition, four cases were found on histological review of a series of osteosarcomas. From this re-examination, twenty-four patients with genuine fibrosarcoma of bone were identified; twenty-two had primary neoplasms and two secondary. No sex or geographical differences were found. The tumours showed a prevalence for patients in the adult and older age groups. Half of the tumours arose from femoral or tibial metaphysial bone adjacent to a knee joint. All the tumours were of the medullary type. Almost one-third presented with a pathological fracture, and soft-tissue extension had occurred in all but three tumours. In contrast to previous reports, these tumours were more malignant than osteosarcomas and showed a five-year survival rate of only 4-2 per cent. In accessible sites, ablative surgery was used as the primary treatment, Fibrosarcoma of bone is a distinctive lesion and should be distinguished carefully from periosteal and soft-tissue fibrosarcomas because of differences in prognosis and treatment.

Biopsy, Needle