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Biomedical subjects

H Johansson

Publications and source records attributed to H Johansson.

At least 199 records · Page 11Linked to original sources
PubMed1988

1,25(OH)2D3 inhibits hormone secretion and proliferation but not functional dedifferentiation of cultured bovine parathyroid cells.

Increasing the extracellular Ca2+ concentration from 0.5 to 3.0 mM induced marked increments in cytoplasmic Ca2+ concentration (Ca2+i) and inhibition of parathyroid hormone (PTH) release of freshly isolated bovine parathyroid cells. 1,25-dihydroxycholecalciferol (1,24(OH)2D3; 0.1-100 ng/ml) did not affect (Ca2+i) and was also without acute effect on the secretion. During 4 days of monolayer culture, the parathyroid cells underwent significant increases in both number and size, and presence of 10-100 ng/ml 1,25(OH)2D3 almost completely inhibited the cell proliferation, whereas the hypertrophy was unaffected. One day of culture with 0.1-100 ng/ml 1,25(OH)2D3 was without effect on PTH release but after 4 days there was a dose-related reduction of secretion. At this time point and irrespective of the culture condition, PTH release was no longer suppressed by high extracellular Ca2+. Furthermore, Ca2+i increased little upon increments in the extracellular Ca2+ concentration as compared with freshly isolated cells. It is concluded that after prolonged exposure to 1,25(OH)2D3, PTH release is inhibited and, at high concentrations, the parathyroid cells cease to proliferate. However, 1,25(OH)2D3 does not affect the development of functional dedifferentiation of parathyroid cells during monolayer culture.

Animals↗
PubMed1988

Calcium-agonistic action of Mn2+ in the parathyroid cell.

The effects of 3.0 mM Mn2+ on parathyroid hormone (PTH) release, 45Ca fluxes and the cytoplasmic Ca2+ concentration (Ca2+i) were studied in vitro with use of parathyroid glands from rats and cattle. Mn2+ inhibited PTH release by about 70 and 60% at Ca2+ concentrations of less than 10 nM or 0.5 mM, respectively, and like the inhibitory effect of Ca2+, that of Mn2+ was rapid and reversible. Mn2+-induced inhibition of the PTH release was associated with reduction of 45Ca uptake by about 50% and a marked but temporary increase in 45Ca efflux. Mn2+ induced a rapid transient increase in Ca2+i provided that the intracellular release of Ca2+ had not already been triggered by previous exposure to 3.0 mM Ca2+. This initial action was apparently followed by influx of Mn2+, since pronounced quenching of the fluorescence from the Ca2+ indicator fura-2 was observed. The results indicate that Mn2+ behaves in several respects like a calcium analogue in parathyroid cells and may inhibit PTH release by interfering directly with the secretory machinery.

Animals↗
PubMed1988

Tissue calcification and alkaline phosphatase activity in uraemic rats.

The activity and localization of alkaline phosphatase activity (AP) in aorta and heart, and the incidence of calcifications in aorta, heart and kidney as well as cardial fibrosis were studied in uraemic rats treated with 1,25-dihydroxycholecalciferol (1,25-DCHH) and Nifedipine. 1,25-DHCC treatment elevated the serum Ca x P product and aggravated the development of renal and aortic calcifications and cardial fibrosis. Nifedipine did not protect against calcifications, but decreased the incidence of cardial fibrosis. The activity of AP was increased in the thoracic aorta in uraemia independent of 1,25-DHCC or Nifedipine treatment or presence of calcification. No changes of the AP activity were found in the heart.

Alkaline Phosphatase↗
PubMed1988

Inhibition of cell growth retains differentiated function of bovine parathyroid cells in monolayer culture.

Monolayer culture of bovine parathyroid cells for up to 4 days in medium containing 10% serum resulted in cell hypertrophy and proliferation as well as functional dedifferentiation. Compared to freshly isolated cells there was a right-shifted dose-effect relationship for calcium-inhibited parathyroid hormone (PTH) release, a decreased suppressibility of secretion and an inability of the cytoplasmic Ca2+ concentration (Ca2+i) to follow changes in the extracellular Ca2+ concentration. The functional changes seemed not to be due to culture per se, since human parathyroid cells exhibited an essentially unchanged regulation of Ca2+i even after 8 days of culture in 10% serum. During culture in medium containing 0.1% serum, the bovine cells did not proliferate and there was only slight cell hypertrophy. These cells retained much of their ability to regulate Ca2+i and PTH release. The results indicate that functional dedifferentiation of parathyroid cells is related to cell growth.

Animals↗
PubMed1987

Fusimotor reflexes to antagonistic muscles simultaneously assessed by multi-afferent recordings from muscle spindle afferents.

Several single agonist/antagonist primary muscle spindle afferents were simultaneously recorded in chloralose anaesthetized cats. It was shown that their dynamic and static sensitivity to sinusoidal muscle stretches could be increased or decreased via the fusimotor system by extension and flexion of the contralateral hind limb as well as by stretch of ipsilateral muscles and stimulation of ipsilateral skin nerves. The results seem to support the hypothesis that the primary muscle spindle afferents convey complex multisensory messages to the central nervous system (CNS).

Afferent Pathways↗
PubMed1987

The actions of arginine and glucose on glucagon secretion are mediated by opposite effects on cytoplasmic Ca2+.

Cytoplasmic Ca2+ (Ca2+i) was monitored in single guinea-pig pancreatic alpha 2-cells exposed to modulators of glucagon release. The stimulatory amino acid arginine raised Ca2+i from 62 to 160 nM, whereas the inhibitor glucose reduced both the latter concentration and basal Ca2+i by 30%. Epinephrine which potentiates arginine-stimulated secretion by increasing cAMP, does so without affecting Ca2+i. The results indicate that glucagon secretion is positively modulated by Ca2+i. It is suggested that glucose-induced lowering of Ca2+i is a fundamental effect in cells where the sugar is readily metabolized.

Animals↗
PubMed1987

Treatment of hormone-producing adrenocortical cancer with o,p'DDD and streptozocin.

Three patients with advanced adrenocortical carcinoma were treated with a combination of intermittent streptozocin and continuous o,p'DDD. Two patients were treated preoperatively and the primary tumors, initially considered as inoperable, could be resected after 19 and 5.5 months, respectively. In the patient with the longer treatment (35 months), lung and lymph node metastases disappeared and she has no evidence of recurrent disease 6.5 years after start of therapy. One patient was followed by magnetic resonance imaging (MRI) and urinary steroid secretion. The MRI gave a good visualization of the tumor. Measurements of relaxation times showed a significant decrease in T1 values. The urinary steroid profile showed an increased secretion of 3 beta-hydroxy-5-ene steroids and tetrahydro-11-deoxy-cortisol. Treatment with streptozocin and o,p'DDD initially increased 16-oxygenation of dehydroepiandrosterone and androst-5-en-3 beta,17 beta-diol, followed by a decrease in the secretion of all urinary steroids. The third patient received postoperative treatment with no effect on metastatic disease in the lungs, she died 9 months after start of treatment. The therapeutic approach with the combination regimen of streptozocin and o,p'DDD pretreatment plus aggressive surgery has to be further evaluated, as well as MRI and urinary steroid profile as methods to monitor the effect of therapy.

Adrenal Cortex↗
PubMed1987

Monoclonal anti-parathyroid antibodies interfering with a Ca2+-sensor of human parathyroid cells.

Previous findings indicate that binding of Ca2+ to an external receptor is part of the mechanism by which extracellular Ca2+ regulates cytoplasmic Ca2+ and hormone release of parathyroid cells. We now present evidence that two newly generated monoclonal anti-parathyroid antibodies react with structures involved in this sensing and/or gating of Ca2+. Microfluorimetric studies of fura 2-loaded human parathyroid cells thus revealed that the antibodies competed with Ca2+ and antagonized the rise in cytoplasmic Ca2+ normally obtained when parathyroid cells are exposed to increasing concentrations of extracellular Ca2+.

Antibodies, Monoclonal↗
PubMed1987

Cytoplasmic Ca2+ concentration of single normal human and bovine parathyroid cells measured by dual wavelength microfluorometry.

Dual wavelength microfluorometry was utilized to measure the cytoplasmic calcium concentration (Cai2+) of single parathyroid cells loaded with the indicator fura-2. The method enabled the first registrations of Cai2+ of normal human parathyroid cells, available only in minute numbers. At 0.5 mM extracellular Ca2+, the Cai2+ levels were similar in normal human and bovine cells. Both cell types responded with an initial Cai2+ transient followed by a sustained increase when raising extracellular Ca2+ to 3.0 mM. The sustained effect exhibited a sigmoidal relation to extracellular Ca2+ in the 0.5-3.0 mM range. Although the increase was somewhat greater in the human cells, the half maximal responses were obtained at almost identical extracellular Ca2+ concentrations. Whereas K+ depolarization decreased Cai2+, the Ca2+ channel blocker D-600 had dual actions, raising Cai2+ at 0.5 mM Ca2+ and decreasing it at 3.0 mM Ca2+, and the effects were similar in the bovine and human cells. The present experimental approach verified the validity of utilizing bovine cells as controls in studies of human parathyroid tissue and it appears suitable for analysis of the role of different subpopulations of parathyroid cells in the abnormal parathyroid tissue of patients with hyperparathyroidism.

Animals↗
PubMed1987

The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect.

The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.

Aged↗
PubMed1987

Patients with primary hyperparathyroidism operated on over a 24-year period: temporal trends of clinical and laboratory findings.

Temporal trends of clinical and laboratory data of 441 patients operated upon for primary hyperparathyroidism (HPT) during 1956-1979 were analysed retrospectively. There was a marked increase in the number of operations for HPT during that time period, from 32 during 1956-1964 to 326 in 1970-1979. In parallel there was a decrease in the proportion of patients with classical manifestations of HPT such as renal stones or bone disease, the latter being on the whole rarely seen in this population. The increased number of operations was instead largely attributable to the more frequent diagnosis of HPT in patients with vague psychiatric or neuromuscular symptoms or with no clinical manifestations; the majority of these persons were older women, the proportion of operations in women 45 years of age or older, increasing from 56% during 1956-64 to 71% during 1970-79. The increased number of operations for HPT during the last decades should be mainly the consequence of a greater awareness of the disease.

Adenoma↗
PubMed1987

Monoclonal antibodies with exclusive reactivity against parathyroid cells and tubule cells of the kidney.

Four monoclonal anti-parathyroid antibodies were generated after immunization of mice with intact cells from human parathyroid tissue. All four monoclonal antibodies reacted in immunohistochemistry with structures present on parathyroid epithelial cells and proximal-tubule cells of the kidney but were unreactive with all other human tissues investigated. Immunofluorescence microscopy on suspended human parathyroid cells showed that the antibodies reacted with structures present on the cell surface. Two of these antibodies efficiently blocked the increase in cytoplasmic calcium concentration of parathyroid cells that is normally associated with increased concentrations of extracellular calcium. The results indicate that these two antibodies interfere with a calcium-sensing mechanism of parathyroid cells--i.e., a potential calcium receptor by which extracellular calcium regulates cytoplasmic calcium and hormone release in these cells.

Animals↗
PubMed1987

Clodronate treatment in patients with malignancy-associated hypercalcemia.

The possibility of reducing symptomatic hypercalcemia and of maintaining total serum calcium concentrations less than 2.8 mmol/l with clodronate (dichloromethylene bisphosphonate) was evaluated in 28 patients with various types of malignant tumors. Four episodes of hypercalcemic crisis with mean serum calcium concentrations of 4.43 mmol/l were controlled within 4-6 days of intravenous clodronate (4 mg/kg BW/day). This was accompanied by a moderate increase in serum creatinine values which, however, returned to pretreatment levels after therapy withdrawal in all but one case. Oral clodronate successfully reduced a mean serum calcium concentration of 3.16 mmol/l in 22 out of 25 patients after 3-12 days (800-3,200 mg/day). After reversal of the hypercalcemias oral clodronate controlled the serum calcium concentration for up to 42 weeks in six out of 15 patients After discontinuation of initial therapy five of seven recurrent hypercalcemias were successfully treated with oral or intravenous clodronate. Hypocalcemia and subjective side-effects were uncommon. It is concluded that clodronate is a valuable clinical tool in the management of patients with malignancy-associated hypercalcemia.

Administration, Oral↗
PubMed1987

Non-Hodgkin lymphoma. Multivariate analysis of prognostic factors including fraction of S-phase cells.

In a material of 80 patients with non-Hodgkin lymphoma a multivariate analysis was carried out taking the following variables into account: Age, clinical stage, B-symptoms, morphologic diagnosis and fraction of S-phase cells in the tumour determined by flow cytometry. Clinical stage, proportion of cells in the S-phase, and age of the patient were significant independent prognostic factors. Morphologic malignancy grade and B-symptoms were not significant parameters in this analysis. It was concluded that DNA analysis with determination of the fraction of S-phase cells is a valuable complement to morphology in the evaluation of patients with non-Hodgkin lymphoma. In combination with the clinical stage it gives very good discrimination into groups with different prognoses.

Adult↗
PubMed1987

Hexokinase and adenylate kinase activities in aorta, heart muscle and skeletal muscle from uraemic rats.

The effect of parathyroidectomy and/or vitamin D on the development of arterial and myocardial lesions was studied in rats with moderate uraemia. The activities of hexokinase and adenylate kinase in the aorta, myocardium and skeletal muscle were measured and the incidence of aortic calcification and muscle cell necrosis determined. There was a decreased hexokinase activity in the aorta, myocardium and skeletal muscle from uraemic rats. Adenylate kinase showed an increased activity in the same tissues. Parathyroidectomy as well as I-alpha-hydroxycholecalciferol in a dose of 3 ng/100 g b.w. normalized these activities to a great extent. This effect did not occur when 10 ng/100 g b.w. was given. Parathyroidectomy in combination with a low dose of I-alpha-OH-D3 reduced the incidence of myocardial necrosis. Aortic calcifications were found in uraemic animals given 10 ng/100 g b.w. of I-alpha-hydroxycholecalciferol. In this group increased activity of adenylate kinase was found in calcified aortae but not in non-calcified aortae. The study shows that uraemia causes metabolic changes in the aorta, myocardium, and skeletal muscle which may partly be prevented by parathyroidectomy and by low doses of vitamin D. It also indicates some parallelism between these metabolic changes and the development of histologically demonstrable lesions in the aorta.

Adenylate Kinase↗