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Biomedical subjects

M R Stjernholm

Publications and source records attributed to M R Stjernholm.

11 recordsLinked to original sources
PubMed1999

Insulin promotes phosphorylation and activation of geranylgeranyltransferase II. Studies with geranylgeranylation of rab-3 and rab-4.

Rab proteins play a crucial role in the trafficking of intracellular vesicles. Rab proteins are GTPases that cycle between an inactive GDP-bound form and an active GTP-bound conformation. A prerequisite to Rab activation by GTP loading is its post-translational modification by the addition of geranylgeranyl moieties to highly conserved C-terminal cysteine residues. We examined the effect of insulin on the activity of geranylgeranyltransferase II (GGTase II) in 3T3-L1 fibroblasts and adipocytes. In fibroblasts, insulin increased the enzymatic activity of GGTase II 2.5-fold after 1 h of incubation, an effect that is blocked by perillyl alcohol, an inhibitor of prenyltransferases, but not by the geranylgeranyltransferase I inhibitor, GGTI-298, or the farnesyltransferase inhibitor, alpha-hydroxyfarnesylphosphonic acid. Concomitantly, insulin stimulated the phosphorylation of the GGTase II alpha-subunit without any effect on the GGTase II beta-subunit. At the same time, insulin also increased the amounts of geranylgeranylated Rab-3 in 3T3-L1 fibroblasts from 44 +/- 1.2% in control cells to 63 +/- 3.8 and 64 +/- 6.1% after 1 and 24 h of incubation, respectively. In adipocytes, insulin increased the amounts of geranylgeranylated Rab-4 from 38 +/- 0.6% in control cells to 56 +/- 1.7 and 60 +/- 2.6% after 1 and 24 h of incubation, respectively. In both fibroblasts and adipocytes, the presence of perillyl alcohol blocked the ability of insulin to increase geranylgeranylation of Rab-4, whereas GGTI-298 and alpha-hydroxyfarnesylphosphonic acid were without effect, indicating that insulin activates GGTase II. In summary, insulin promotes phosphorylation and activation of GGTase II in both 3T3 L1 fibroblasts and adipocytes and increases the amounts of geranylgeranylated Rab-3 and Rab-4 proteins.

3T3 Cells↗
PubMed1980

Medullary carcinoma of the thyroid before age 2 years.

An 18-month-old infant was evaluated for medullary thyroid carcinoma (MTC) because of a maternal history of the tumor and the presence of characteristic mucosal abnormalities. Although examination of the thyroid gland was normal, RIA of plasma calcitonin reveled elevated basal levels of the hormone and the patient underwent total thyroidectomy at 23 months of age. Histological examination of the tumor was consistent with the diagnosis f MTC, and this diagnosis was confirmed by immunohistology. The earliest feasible evaluation for MTC should be performed in children of an affected family.

Adolescent↗
PubMed1977

Factitious hypoglycemia. Diagnosis by measurement of serum C-peptide immunoreactivity and insulin-binding antibodies.

In seven patients with factitious hypoglycemia due to the surreptitious injection of insulin, we made the diagnosis by measurements of plasma insulin and C-peptide immunoreactivity (in seven patients), facilitated by the finding of circulating insulin-binding antibodies (in two patients). The simultaneous demonstration of low plasma glucose, high immunoreactive insulin and suppressed C-peptide immunoreactivity represents a triad of results pathognomonic of exogenous insulin administration. Determination of plasma free C-peptide and free insulin permitted patients with high titers of insulin antibodies, including those with a history of insulin-treated diabetes, to be studied and diagnosed in a way similar to that in subjects who had no circulating insulin antibodies.

Adenoma, Islet Cell↗
PubMed1976

Clinical correlations of serum proinsulin-like material in islet cell tumours.

To examine the possibility that the concentration of circulating proinsulin-like material (PLM) might be helpful in evaluating the therapeutic response of patients with islet cell tumours, serum levels of PLM in three patients with islet cell tumours were correlated with hypoglycaemic symptoms and plasma glucose concentrations before and after treatment. In two patients ranges of fasting PLM concentration were 0.21-0.29 and 0.91-0.93 ng/ml, respectively, before treatment. After surgical excision of their islet cell adenomas, PLM concentrations decreased to 0.06-0.09 and 0.03-0.05 ng/ml. Insulin concentrations were low preoperatively in both patients and were unchanged postoperatively. The resulting relief from hypoglycaemia was paralleled by a reduction of PLM, with no significant change in insulin. In a third patient, treatment with streptozotocin resulted in marked symptomatic improvement, a 65% reduction in PLM concentration, but no significant change in insulin levels. Relapse was associated with increasing frequency of hypoglycaemic symptoms and increasing PLM concentrations. These findings suggest that changes in the levels of serum PLM may prove to be a sensitive indicator of the response of islet cell tumours to therapy.

Adenoma, Islet Cell↗
PubMed1975

Growth hormone release after synthetic 1-24 ACTH: effects of estrogen and sex.

Recent reports have demonstrated that growth hormone (GH) is inconsistently released after intravenous administration of synthetic 1-24 ACTH. This study was designed to evaluate the role of estrogens in mediating this response. 250 mug of synthetic 1-24 ACTH were administered to 8 men in 12 studies and 6 women in 11 studies. None of the men exhibited a rise in GH after 1-24 ACTH, while the women exhibited a significant increase. Pretreatment of 5 of these men with 100 mug of ethinyl estradiol daily for 3 days did not alter GH response from the initial studies. Pretreatment with 10 mg of diethylstilbesterol daily for 3 days, however, resulted in a rise in GH which was similar to the female group. It is concluded that the variable GH responses to synthetic 1-24 ACTH may be in part due to prevailing concentrations of sex steroids and their effect on the hypothalamic-pituitary GH release mechanism.

Adrenocorticotropic Hormone↗
PubMed1975

Effects of diphenylhydantoin, phenobarbital, and diazepam on the metabolism of methylprednisolone and its sodium succinate.

The metabolic clearance rates (MCR) of methylprednisolone (MP) (no. = 13) and methylprednisolone-21- Na-hemisuccinate (MPHS) (no. = 6) were studied in normal humans using tritium-labeled steroids. The cumulative appearance of the labeled steroid was examined for the whole urine and for three major urinary fractions. The MCR, half-life, and volume of distribution were, respectively, 383 +/- 72 (SD) liters/day, 165 +/- 49 minutes, and 61 +/- 12 liters for MP, and 234 +/- 37, 160 +/- 19, and 41 +/- 6 for MPHS. Diphenylhydantoin (DPH) administered to 4 subjects increased the MCR of MP from 424 +/- 71 to 977 +/- 132 (P less than 0.01), and decreased the half-life from 149 +/- 44 to 69 +/- 7 (P less than 0.001). Similar effects were found with phenobarbital (PB). Diazepam (DZP) had no effect. Major increases in urinary metabolites after DPH and PB were in the unconjugated ethyl acetate fraction, and this suggests that MP metabolism is significantly altered by hepatic microsomal hydroxylation enzyme induction by DHP and PB, but not DZP. This could occur with the formation of a 6beta-hydroxy derivative which could be readily cleared by the kidney. The urinary pattern of excretion for MPHS was similar to that of MP. The MCR of MPHS was affected to a lesser extent by DPH and PB than was the MCR of MP(P less than 0.01). Therefore, the use of hepatic microsomal hydroxylase inducers should be taken into consideration in clinical states in which MP is being used.

Adult↗
PubMed1975

Thyroid-function tests in diphenylhydantoin-treated patients.

We compared the free-thyroxine index in normal adults and in euthyroid patients taking diphenylhydantoin. All subjects had normal serum thyrotropin concentrations. Serum thyroxine concentrations were determined by two commonly used competitive protein-binding assays, which yielded slightly different values, but which consistently showed the same degree of decrease in mean serum thyoxine concentration in drug-treated patients as compared to the normal subjects. When 14C-labeled diphenylhydantoin was added to serum before the assay, it was separated from thyroxine in the Ames method, whereas by the Murphy-Pattee method both drug and thyroxine were extracted together. Thus, the decrease in serum thyroxine concentrations during diphenylhydantoin therapy cannot be the result of drug interference with the binding of thyroxine to binding proteins in the assays. Triiodothyronine uptake, evaluated by two methods, was identical in the two groups. The free-thyroxine indexes for all normal persons were within the manufacturer's normal range, but 21% of the drug-treated patients had subnormal indexes by the Ames method; the indexes as measured by the Murphy Pattee method were in the lower half of the normal range. Because the triiodothyronine uptake was unaffected by the drug treatment, the decreases in the indexes must have resulted from the lower serum thyroxine concentrations. We conclude that the free-thyroxine index may not provide a valid estimate of either the clinical status or the free-thyroxine concentration in patients taking diphenylhydantoin.

Adult↗
PubMedDate not supplied

Cardiac tamponade in myxedema.

Pericardial effusions are frequently found in myxedema and , when present, are asymptomatic and usually of no hemodynamic consequence. We report a patient with ascites and pericardial effusion due to myxedema who developed cardiac tamponade following abdominal paracentesis. This case emphasizes that treatment of patients with myxedematous chronic pericardial effusions should include avoidance of those measurements which may reduce venous filling pressure or effective cardiac output regardless of the thyroid status.

Adult↗