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Biomedical subjects

L Boquist

Publications and source records attributed to L Boquist.

At least 55 records · Page 3Linked to original sources
PubMed1983

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↗
PubMed1982

Prognostic factors in chondrosarcoma: a comparative study of cellular DNA content and clinicopathologic features.

In a retrospective study of 45 surgically treated chondrosarcomas, the prognostic significance of the cellular DNA content and different clinicopathologic factors was analyzed with separately and in combination. The relationship between these parameters was also investigated. Diploid (normal DNA content) chondrosarcomas were associated with as significantly (P less than 0.001) higher ten-year survival rate than hyperploid (abnormally increased DNA content) chondrosarcomas. Apart from ploidy, factors such as tumor size, tumor location and tumor grade also proved to be of prognostic importance. However, patients with diploid tumors had a better prognosis than those with hyperploid tumors, almost regardless of location, size, grade or even treatment. Nevertheless, additional prognostic information could be obtained by combining ploidy with size, location and grade of the tumors. Ploidy and treatment were significantly related to the ten-year recurrence rate. No statistical relationship could be demonstrated between ploidy and other prognostic factors. A strong correlation (P less than 0.001) was, however, found between location and size of the tumors. Thus, distal tumors were significantly smaller and, moreover associated with a better prognosis than axial tumors. The results indicate that ploidy probably is the best predictor of the clinical course in chondrosarcoma. While tumor location and size may be assumed to determine the conditions for radical surgery, ploidy and grade seem to reflect the inherent biological malignancy in chondrosarcoma. Consideration of these factors seems to provide not only valuable prognostic information, but also guidelines for treatment.

Adolescent↗
PubMed1982

Optical diffraction analysis of crystalline inclusions in the rough endoplasmic reticulum of islet parenchymal cells of the hagfish, Myxine glutinosa.

Optical diffraction analysis was carried out on crystalline inclusions in the rough endoplasmic reticulum of the insulin and somatostatin cells in the islet organ of the hagfish. A striking difference in crystalline arrangement was observed between the inclusions of the insulin and somatostatin cells. The crystallographic arrangement of the inclusions observed in situ in the insulin cells differed from that previously found by means of X-ray diffraction analyses of hagfish insulin crystals formed in vitro.

Animals↗
PubMed1982

Effects of alloxan and streptozotocin on calcium transport in isolated mouse liver mitochondria.

The effect of alloxan and streptozotocin on the fluxes of Ca2+ in isolated mouse liver mitochondria was studied with dual wave-length spectrophotometry, using antipyrylazo III as metallochromic indicator. Streptozotocin had no effect on Ca2+ uptake, whereas alloxan inhibited the initial rate and extent of Ca2+ influx in a way dependent on the duration of preincubation, and occurrence of Pi in the reaction mixture. A rapid release of Ca2+ followed upon addition of either FCCP or alloxan after the reaction had been started. When added to preloaded mitochondria, alloxan induced a concentration dependent release of Ca2+. The data suggest that alloxan induces an initial release of mitochondrial Ca2+, which is followed by inhibition of Ca2+ influx. The initial release may be due to uncoupler activity induced by alloxan, and the inhibition of Ca2+ influx may be a consequence of inhibited Pi transport.

Alloxan↗
PubMed1982

Effect of alloxan on phosphate transport in isolated mouse liver mitochondria: influence of pH, and differentiation between influx and efflux of phosphate.

The effect of alloxan on inorganic phosphate (Pi) transport in isolated mouse liver mitochondria was studied by swelling techniques. Mitochondria preincubated with alloxan exhibited inhibition of Pi uptake assessed by NH4-Pi, K+-ionophore and acetate/Pi exchange systems, and also inhibition of Pi efflux assessed by the K+-ionophore and FCCP1-ATP systems. The effect on Pi uptake was pH dependent. Swelling in the FCCP-ATP system in the presence of alloxan and NEM was unaffected by rotenone and cysteine but was blocked by oligomycin, whereas the swelling caused by mersalyl was unaffected by rotenone, blocked by oligomycin, and reversed by cysteine. Alloxan stimulated mitochondrial ATPase activity, this effect being blocked by oligomycin. These findings suggest that alloxan causes an irreversible and pH-dependent inhibition of Pi influx and efflux in isolated mouse liver mitochondria.

Adenosine Triphosphatases↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1981

Manifestation and growth of a transplantable osteosarcoma in mice: the effects of thymectomy and thymosin treatment.

Normal and thymectomized CBA mice treated with and without thymosin were injected with 2 x 10(6) viable osteosarcoma cells. The activity and weight of tumors, the cell-mediated and humoral-immune responses against the tumors, and the light microscopic characteristics suggested that thymectomy resulted in a significantly decreased tumor frequency. There were also significant increases in cell-mediated cytotoxic activity in vitro as measured by lysis of 51Cr-labeled tumor cells incubated with spleen cells, and in lymphocytic infiltration around the tumors. While thymosin treatment of thymectomized mice restored these parameters to those of intact animals, thymosin had no demonstrable effects on nonthymectomized animals.

Animals↗
PubMed1981

Effect of alloxan on phosphate transport in isolated mouse liver mitochondria.

The swelling technique was used to study the transport of inorganic phosphate (Pi) in isolated mitochondria from mouse liver. Mitochondria preincubated with alloxan exhibited an early inhibition of Pi uptake, which was dependent both upon the concentration of alloxan and the duration of the reaction with alloxan. No significant inhibition was found with 1 mM alloxan, whereas 10 mM alloxan caused approximately 50 percent inhibition. Maximum inhibition was observed at 2 min with 10 mM alloxan, and at 10 min with 2.5 mM alloxan. Alloxan did not significantly affect the swelling of mitochondria preincubated with acetate, indicating that the inhibition by alloxan of Pi uptake is due to an action of the drug on the Pi carrier (Pi/OH-). The findings support our Pi-pH hypothesis for the development of alloxan diabetes.

Alloxan↗
PubMed1980

Calcium and pancreatic beta-cell function. The mechanism of insulin secretion studied with the aid of lanthanum.

La3+ was used to study the involvement of Ca2+ in insulin secretion in beta-cell-rich pancreatic islets micro-dissected from non-inbred ob/ob mice. Ultrastructural studies revealed that the localization of La3+ was entirely restricted to the exterior of the cells. Consistent with a membrane action, exposure to La3+ failed to affect glucose oxidation and either the sucrose space or the general ultrastructure of the islets. In contrast, La3+ had marked effects on insulin release and 45Ca fluxes. Exposure to La3+ resulted in pronounced inhibition of insulin release irrespective of the presence or absence of Ca2+, 3-isobutyl-1-methylxanthine or glucose. Perifusion experiments revealed that the inhibitory action was prompt, sustained and readily reversible. Removal of La3+ was associated with a subsequent prolonged stimulatory phase of insulin release even in medium deficient in Ca2+. This action could not be attributed to an increase in cyclic AMP, but was potentiated by 3-isobutyl-1-methylxanthine and abolished by L-adrenaline. La3+ displaced 45Ca from superficially located binding sites and inhibited the uptake and efflux of 45Ca. The stimulatory and inhibitory actions of glucose on 45Ca efflux were also abolished in the presence of 2 mM-La3+ Removal of La3+ was associated with the preferential mobilization of 45Ca incorporated in response to glucose. The results indicate that binding of La3+ to superficial sites in the plasma membrane leads to inhibition of insulin release by suppression of transmembrane Ca2+ fluxes. It is suggested that accumulation of Ca2+ in the cytoplasm accounts for the stimulation of insulin release seen after removal of La3+ from inhibitory binding sites in the beta-cell plasma membrane.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Hyperglycemia produced in mice by administration of acetazolamide and diphenylhydantoin.

Isolated mouse islets exposed to 3mM glucose released an increased amount of insulin in the presence of acetazolamide (AZM) (10 mM) and diphenylhydantoin (DPH) (0.35 or 3.5 mM), whereas insulin secretion due to 20 mM glucose was decreased in the presence of AZM (10 mM) and DPH (0.35, 0.70 or 3.5 mM). The serum insulin concentration was increased 1 h after AZM injection, but was not significantly altered 1 h after combined administration of AZM and DPH. A moderate transient hyperglycemia was found 1 and 2 h after DPH injection (100 mg/kg b.w.) in fed mice, and a slight, transient hyperglycemic response was observed 24 h after administration of AZM (1.5 g/kg b.w.) to fed mice. A steadily increasing, marked hyperglycemia was seen in both fed and starved mice when AZM was given shortly before or after DPH. All animals subjected to this kind of treatment died within 48 h after the injections. Ketones were found in urine and serum of the hyperglycemic animals, and the hyperglycemia was abolished and the survival of the animals was prolonged by insulin administration, suggesting that ketoacidosis contributed to the death. Light microscopy disclosed degeneration and necrosis of some B-cells, and occasionally insulitis after combined treatment with AZM and DPH. Pretreatment with AZM inhibited the hyperglycemic response to p-hydroxymercuribenzoate in fed mice, but did not affect the hyperglycemic response of fed mice to D-mannoheptulose. The findings indicate that AZM and DPH, when given to mice in combination and in sufficient amount, cause impaired B-cell function with an inhibited glucose-induced insulin release and a severe, fatal hyperglycemia. The B-cell changes are believed to be due to intracellular ionic alterations.

Acetazolamide↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1980

A new hypothesis for alloxan diabetes.

A new hypothesis ("Pi-pH hypothesis") for alloxan diabetes is presented. It is based upon data from our own studies and from the literature. The following data and interpreatations are assumed to be of special importance for the B-cytotoxicity of alloxan: Inhibition of a mitochondrial sulfhydryl dependent transport system for inorganic phosphate (Pi) leading to increased concentration of Pi and decreased pH in the cytosol, and to inhibition of NAD-dependent oxidations and oxidative phosphorylation; mitochondrial lesion because of altered localization and concentration of Pi; inhibited synthesis and glucose induced release of insulin, at least partly due to a fall in intracellular pH; and finally necrosis because of absent mitochondrial function. An inverse relationship between Pi and pH may exist in the B-cells; alloxan sensitivity being associated with high Pi and low pH. Alloxan antagonism may be due to induction of low Pi and high pH in the cytosol. The selectivity of the B-cell for alloxan is believed to be associated with its free permeability for glucose.

Alloxan↗
PubMed1980

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↗