Search PubMed⌕ Search

Biomedical subjects

C Rasmussen

Publications and source records attributed to C Rasmussen.

At least 73 records · Page 4Linked to original sources
PubMed1993

Activation of calmodulin-dependent enzymes can be selectively inhibited by histone H1.

Calmodulin (CaM) and its target enzymes are important regulators of a variety of cellular processes including gene expression and cell cycle progression (Bading, H., Ginty, D. D., and Greenberg, M. E. (1993) Science 260, 181-186; Rasmussen, C. D., and Means, A. R. (1989) EMBO J. 8, 73-82). It has been previously accepted that regulation of CaM-dependent enzyme activity occurs via calcium/calmodulin-dependent activation. We have found that histone H1 is a potent inhibitor of the CaM-dependent activation of mouse calcium/calmodulin-dependent protein kinase II (CaMKII) and of the CaM-dependent protein phosphatase, calcineurin. Inhibition is mediated only by free histone H1; addition of DNA abolishes the inhibitory effect. The effect is not due to a simple interaction of basic (histone) and acidic (CaM) proteins since myelin basic protein and histone H2B, CaMKII substrates more basic than histone H1, did not affect autophosphorylation of CaMKII, and myelin basic protein had no effect on calcineurin activity. The effect is specific to CaM since addition of parvalbumin, a related Ca(2+)-binding protein, did not reverse the effect of histone H1, whereas addition of CaM recovered enzyme activity. These results indicate that free histone H1 levels may specifically affect the ability of CaM to activate its target enzymes and suggests a novel level of control of CaM-dependent enzymes in eukaryotic cells.

Animals↗
PubMed1993

Mitochondrial disorder associated with newborn cardiopulmonary arrest.

A female infant who died 2.5 d after birth with hypoglycemia, lactic acidosis, and sudden multisystem failure was studied. Biochemical studies showed complex III and IV deficiency in liver, kidney, and muscle, with muscle most severely affected. Southern blot analysis of the patient's mitochondrial DNA did not reveal any deletions. Denaturing gradient gel analysis, which detects single base changes by differences in melting behavior, showed an extra band that was not seen in mitochondrial DNA from the mother, the mother's identical twin sister, or an unrelated normal subject. This extra band indicated heteroplasmy for a restriction fragment containing the apocytochrome b and transfer RNA(thr) genes. Sequencing revealed an A to G mutation at nucleotide 15923, the last base of the anticodon loop of the transfer RNA(thr) gene. The mutation lengthens the anticodon stem by added pairing and reduces the anticodon loop size from 7 to 5 nucleotides, potentially compromising transfer RNA(thr) function in translation and/or in processing the polycistronic RNA transcript. The patient's mother previously had a male infant who also died at 1.5 d postnatal, and both the mother and her twin have had multiple miscarriages. Amniocentesis for a genetic screen was performed on the mother's twin sister during a recent pregnancy; some of the cultured cells were made available for this study. The mutation was not found in the amniocytes or in umbilical cord blood obtained at birth; the baby was normal at birth and remains healthy. It is concluded that the mutation at nucleotide 15923 was most likely the cause of the fatal disease in the index case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intravenous morphine-induced activation of vagal afferents: peripheral, spinal, and CNS substrates mediating inhibition of spinal nociception and cardiovascular responses.

1. Intravenous administration of 1.0 mg/kg of morphine produces inhibition of the nociceptive tail-flick (TF) reflex, hypotension, and bradycardia in the pentobarbital-anesthetized rat. The present experiments examined peripheral, spinal, and supraspinal relays for inhibition of the TF reflex and cardiovascular responses produced by morphine (1.0 mg/kg iv) in the pentobarbital-anesthetized rat using 1) bilateral cervical vagotomy, 2) spinal cold block or mechanical lesions of the dorsolateral funiculi (DLFs), or 3) nonselective local anesthesia or soma-selective lesions of specific CNS regions. Intravenous morphine-induced inhibition of responses of unidentified, ascending, and spinothalamic tract (STT) lumbosacral spinal dorsal horn neurons to noxious heating of the hindpaw were also examined in intact and bilateral cervical vagotomized rats. 2. Bilateral cervical vagotomy significantly attenuated inhibition of the TF reflex and bradycardia produced by intravenous administration of morphine. Bilateral cervical vagogtomy changed the normal depressor response produced by morphine into a sustained pressor response. Inhibition of the TF reflex in intact rats was not due to changes in tail temperature. 3. Spinal cold block significantly attenuated inhibition of the TF reflex, the depressor response, and the bradycardia produced by intravenous administration of morphine. However, bilateral mechanical transections of the DLFs failed to significantly affect either inhibition of the TF reflex or cardiovascular responses produced by this dose of intravenous morphine. 4. Microinjection of either lidocaine or ibotenic acid into the nuclei tracti solitarii (NTS), rostromedial medulla (RMM), or ventrolateral pontine tegmentum (VLPT) attenuated morphine-induced inhibition of the TF reflex. Similar microinjections into either the periaqueductal gray (PAG) or the dorsolateral pons (DLP) failed to affect morphine-induced inhibition of the TF reflex. 5. Microinjection of either lidocaine or ibotenic acid into the NTS, RMM, VLPT, DLP, or rostral ventrolateral medulla (RVLM) attenuated the depressor response produced by morphine, although baseline arterial blood pressure (ABP) was affected by ibotenic acid microinjections in the DLP. In all these cases, the microinjections failed to reveal a sustained pressor response as was observed with bilateral cervical vagotomy. Similar microinjections into the PAG failed to affect the depressor response produced by morphine. 6. The lidocaine and ibotenic acid microinjection treatments also showed that the bradycardic response produced by morphine depends on the integrity of the NTS, RMM, RVLM, and possibly the DLP, but not the PAG or VLPT.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1991

Clinical response and prolactin concentration in hyperprolactinemic women during and after treatment for 24 months with the new dopamine agonist, CV 205-502.

Twenty-four hyperprolactinemic women of whom 23 previously had been given bromocriptine, were treated between 6 and 24 months with a new non-ergot dopamine agonist, CV 205-502 (quinagolide; Norprolac, Sandoz Ltd, Basle Switzerland). Twenty-four weeks of treatment resulted in normalization of prolactin secretion in 16 of the 24 women. All of these women as well as 4 of those who remained hyperprolactinemic had regular menstrual bleedings. Fifteen of the 24 women were treated for 24 months and all had normalized prolactin levels in serum at the end of this period. Regular menstrual bleedings were observed in 13 women. Mild to moderate galactorrhea was recorded at baseline in 14 of the 15 women. After 24 months of treatment, mild galactorrhea was still present in 3 women. All 15 women had been treated with bromocriptine or other dopamine agonists before they entered the study. In 9 of the women the tolerability had been judged to be fair (N = 4) or poor (N = 5). Five of the 15 women had previously discontinued bromocriptine treatment because of adverse effects but had few problems tolerating CV 205-502. Prolactin in serum increased in all the patients after discontinuation of the medication. The results confirm that CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinemia.

Adult↗
PubMed1990

The occurrence of macroscopical pituitary calcifications in prolactinomas.

Radiographs of the sella turcica from 73 hyperprolactinaemic women, were followed-up for 5 to 13 years. Six women (8%) were found to harbour granular calcific deposits in the anterior part of the sella turcica visible on the plain radiographs. In three women the calcification increased in size during follow-up. This was accompanied by signs of regression of other features of pituitary tumour on the radiographs in two women. Pituitary calcifications associated with hyperprolactinaemia seem to represent a benign and regressive process.

Bromocriptine↗
PubMed1990

Long-term radiographic follow-up of the sella turcica in hyperprolactinaemic women.

Seventy-three hyperprolactinaemic women were followed up with radiographic examinations (lateral and posteroanterior coned down views) of the sella turcica for 5 to 13 years during which time all but one had received treatment with bromocriptine. Progression of the sellar asymmetry occurred in 25 women (7 during pregnancy), 14 had regression of their changes in the pituitary fossa while 34 did not show any changes in the configuration of the sella turcica. Prolactin levels in serum, duration of bromocriptine therapy or sellar configuration could not predict later radiographic progressive or regressive changes of the sella turcica. The clinical course was benign in the majority of the women with signs of prolactin-producing adenomas. The risk of serious tumour enlargement seems to be very small. We were not able to demonstrate any parameter which could predict the growth or shrinkage of the tumour. Routinely repeated radiographic sellar examinations are unnecessary in the vast majority of hyperprolactinaemic women.

Adult↗
PubMed1989

Selegiline and levodopa in early or moderately advanced Parkinson's disease: a double-blind controlled short- and long-term study.

Selegiline 10 mg per day was compared to placebo as an adjunct to levodopa treatment in this double-blind study of early or moderately advanced Parkinson's disease. Thirty-eight patients completed an initial cross-over trial comprising two treatment periods, each of eight weeks, with a four weeks' wash-out period between them. Thirty of the patients continued in a long-term, double-blind parallel trial with a mean duration of 16 months (range 6-30 months). Selegiline treatment allowed a significant reduction of the necessary daily levodopa dose in both parts of the study and of the daily dosing frequency in the long-term investigation. In spite of this reduction of levodopa dose, an improvement was noted in tremor during the short-term selegiline periods. The side-effects were slight and related to dopamine effects and disappeared after reduction of levodopa-dose. The results support the use of selegiline as an early adjunctive treatment in Parkinson's disease.

Aged↗
PubMed1988

Long-term treatment with a new non-ergot long-acting dopamine agonist, CV 205-502, in women with hyperprolactinaemia.

Twenty-four hyperprolactinaemic women were treated for 6 months with the new, non-ergot, long-acting dopamine agonist, CV 205-502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once-daily doses of 0.05 to 0.15 mg of the drug. Sixteen of these women as well as 4 of those who remained hyperprolactinaemic had regular menstrual bleeding. Five of the patients had previously discontinued bromocriptine therapy because of adverse effects but had no problems tolerating CV 205-502. Of three bromocriptine-resistant women, two responded partially while one also remained unresponsive to CV 205-502 treatment. Mild to moderate galactorrhoea was recorded at baseline in 19 of the 24 women. After 6 months' treatment mild galactorrhoea was still present in six patients, four of whom had attained normal PRL levels. Side-effects were mild and transient. CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinaemia.

Adult↗
PubMed1987

Prolactin secretion and menstrual function after long-term bromocriptine treatment.

Long-term bromocriptine treatment was discontinued in 75 hyperprolactinemic women. Bromocriptine had been given for up to 65 months (median, 24 months). Treatment was reinstituted in 42 women (56%) after 1 to 3 months, mainly because of increasing prolactin levels. Thirty-three women (44%) were followed up for 6 months or more without treatment. Menstrual bleeding occurred in 19 of the 33 women (58%) after 6 months without treatment. The mean prolactin concentration in this group had decreased more than 60% compared with pretherapy concentrations. In 18 of the 42 women who had bromocriptine therapy again, treatment was discontinued a second time. Six of these patients have regular menstrual bleeding. Long-term bromocriptine treatment seems to induce long-standing normalization of prolactin secretion in patients with hyperprolactinemia.

Adolescent↗
PubMed1987

CV 205-502: a new long-acting drug for inhibition of prolactin hypersecretion.

CV 205-502, an octahydrobenzo(g)quinoline, is a new non-ergot long-acting prolactin inhibitor. The substance was given to 24 hyperprolactinaemic women for 7 d. The women were randomized to one of three dose regimens, 0.01 mg, 0.03 mg or 0.06 mg daily. Two patients in each group were given placebo. Frequent blood samples were obtained during days 1, 7 and 8. The prolactin levels in serum were depressed dose-dependently in all patients given active substance. In group 1 (0.01 mg) the dose was insufficient to induce normal serum prolactin levels except in one woman, while two women in group 2 (0.03 mg) and four in group 3 (0.06 mg) became normoprolactinaemic. The depressant effect on prolactin secretion lasted for 24 h in group 2 and 3. Side-effects were mild and transient. No change in blood pressure was observed. CV 205-502 was an effective and long-acting drug for treatment of patients with hyperprolactinaemia in this short-term study and this new drug deserves investigation of its usefulness in long-term treatment.

Adolescent↗
PubMed1985

Return of menstruation and normalization of prolactin in hyperprolactinemic women with bromocriptine-induced pregnancy.

Fifty-eight hyperprolactinemic women were followed up for 13 to 108 months after at least one bromocriptine-induced pregnancy for investigation of whether the pregnancy had any adverse long-term effects on the hyperprolactinemic state. Fifteen women had two term pregnancies. The prolactin (PRL) level decreased greater than 50% in 20 women after the pregnancy. Only two women showed a PRL level increase. Spontaneous uterine bleedings returned in 16 women, whereas 42 remained amenorrheic. Thus, bromocriptine-induced pregnancy in women with hyperprolactinemia has no negative long-term effect on PRL secretion.

Adult↗
PubMed1984

Evaluation of normal values for stationary and moving two-point discrimination in the hand.

Stationary and moving two-point discrimination were tested in a normal population stratified by age and sex. The 467 subjects tested consisted of 202 females and 265 males whose ages ranged from 4 years to 92 years. Statistical analysis of the data revealed the following: (1) Moving two-point values were of lesser magnitude than stationary two-point values in all areas tested; (2) test values for median innervated areas were lower by both methods than values for ulnar innervated areas; (3) there was a gradual increase in the magnitude of the test values for both methods with advancing age; (4) female subjects consistently tended to discriminate at shorter distances when compared with male subjects at corresponding sites; and (5) the absolute values obtained were dependent upon the individual examiner, but the statistical significance applied to the data of all of the examiners.

Adolescent↗