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Biomedical subjects

G Massa

Publications and source records attributed to G Massa.

At least 73 records · Page 4Linked to original sources

Subcutaneous recombinant human erythropoietin for the treatment of anemia in myelodysplastic syndromes.

Recombinant human erythropoietin (rhEPO) was administered subcutaneously to 13 anemic (Hb < 10 g/dl) patients with myelodysplasia (MDS). rhEPO was given 3 times a week at doses of 75-250 U/kg body weight, over a maximum period of 24 weeks. Five patients (38%) showed a response to rhEPO treatment. rhEPO was well tolerated and without relevant side effects throughout the study. All responding patients had low but detectable pretreatment circulating erythroid progenitor cells (BFU-E) and the response to rhEPO was associated with a significant increase in BFU-E (p < 0.01); concentrations of serum transferrin receptor (TfR) also consistently rose in all responding patients. Baseline erythropoietin (EPO) concentrations did not significantly differ between responders and nonresponders, although 4 out of the 5 responders had relatively low levels of EPO. In conclusion, subcutaneous rhEPO administration appears to be an effective treatment of anemia in a substantial subset of patients with MDS. Relatively low baseline EPO concentrations, detectable pretreatment circulating BFU-E and an early increase in the serum concentrations of TfR seem to be criteria for predicting response to rhEPO in patients with MDS.

Aged↗

Opposite effects of growth hormone and estrogens on the pregnancy zone protein serum levels in children and adolescents.

Serum levels of pregnancy zone protein were measured in children with growth hormone deficiency and in girls with Turner syndrome, before and during treatment with recombinant human growth hormone and in healthy controls. The pregnancy zone protein serum levels in growth hormone deficiency patients before treatment were significantly higher than in controls (median value 2420 micrograms/l vs 434 micrograms/l; p < or = 0.001). In Turner syndrome patients they were within the normal range. The administration of rhGH to both growth hormone deficiency and Turner syndrome patients resulted in a significant decrease in the serum pregnancy zone protein levels by approximately 50%. The addition of 50 ng.kg-1.d-1 ethinylestradiol to the growth hormone treatment in Turner syndrome patients led to an increase in pregnancy zone protein concentrations in four out of five patients. Elevated pregnancy zone protein levels were also found in two children with growth hormone resistance (Laron type dwarfism). In one patient with placental growth hormone deficiency, pregnancy zone protein serum levels during pregnancy were within the normal range. These results suggest that the serum pregnancy zone protein levels are down-regulated by growth hormone.

Adolescent↗

Comparison between the human serum growth hormone-binding protein and the water-soluble growth hormone-binding site released from IM-9 lymphocytes.

The characteristics of the human serum growth hormone-binding protein (GHBP) were compared with those of a water-soluble GH-binding site prepared by incubating cultured IM-9 lymphocytes in assay buffer with 25 mmol/l iodoacetamide. High-performance liquid chromatography gel filtration of the water-soluble GH-binding site incubated with 125I-labeled human GH ([125I]hGH) revealed a large peak of bound [125I]hGH eluting at the same position as the peak of [125I]hGH bound to the GHBP in serum. The estimated M(r) of the peak was 120,000, presumably representing one [125I]hGH bound to two binding sites. The binding specificities of the serum GHBP, the water-soluble GH-binding site and the GH receptor on IM-9 lymphocytes were identical. The binding affinities for 22,000 hGH and for 20,000 hGH of the serum GHBP were similar to the binding affinity of the water-soluble GH-binding site but lower than those of the cellular GH receptor. These findings show that the characteristics of the serum GHBP are comparable to those of the water-soluble GH-binding site released from IM-9 cells and support the hypothesis that in man the serum GHBP is produced by proteolytic cleavage of the cellular GH receptor.

Binding Sites↗

A soap technique for cell separation to study the seed coat of Sesbania punicea.

A technique is described for separating plant cells used for morphological studies. The plant material is placed in a concentrated solution of olive oil castile soap for 1-2 days or more. The material is then thoroughly washed and placed between two glass slides. The upper glass slide is lifted from the lower one, then gently pressed down several times. Through this procedure Malpighian cells of the seed coat of Sesbania punicea, mesophyll cells of Euphorbia peplus and of Trifolium pratense and cortical cells of the aerial roots of Monstera deliciosa have been separated. Various shapes of the Malpighian cells of the Sesbania punicea seed coat can be observed along with intermediates.

Cell Separation↗

Intelligence, behaviour and psychosocial development in Turner syndrome. A cross-sectional study of 50 pre-adolescent and adolescent girls (4-20 years).

In this paper we report the findings and data on a cross-sectional study of 50 pre-adolescent and adolescent girls with Turner syndrome. We confirm the presence of a typical cognitive profile in the different age groups with normal verbal intelligence contrasting with lower results on performal IQ subtests, related to relative weaknesses on visuospatial subtests i.e. "Block Design" and "Object Assembly". 5% of the girls with a "classical" Turner syndrome karyotype (i.e. 2/40) were mentally retarded versus 30% (i.e. 3/10) in the group with "rare" karyotypic anomalies. We noted a positive influence of hormonal therapy on the visuospatial functioning. No evidence was found for a high risk for behavioural problems. Hyperactive behaviour was seen in the youngest patients contrasting with a tendency to hypoactivity around the age of normal puberty. Problems in social development were noted from the age of primary school on resulting in social immaturity and even isolation. A proposal for guidance of Turner girls during the different developmental periods is given.

Adolescent↗

Endothelium-mediated relaxation in transplanted aorta.

This study compares the vasodilating effect of endothelium-derived relaxing factors (EDRFs) in free arterial grafts with that in their normal control vessels. The infrarenal aorta of Sprague-Dawley rats was transplanted into the same position in other inbred recipient rats. A Krebs buffer solution (4 degrees C) served as the preservation solution. The ischemic time for the grafts (n = 8) was 42 +/- 1 minutes. Two grafts were studied after 3 days and six grafts, after 60 days. Ring segments were cut from all vessels, and isometric contractions were recorded in organ baths. The vessel segments were constricted with noradrenaline, a thromboxane A2 mimic (U-46619), or prostaglandin F2 alpha. Concentration-response curves with acetylcholine, which was used as the endothelium-stimulating substance causing release of EDRFs, were obtained. The patency of the grafts was 100%. Acetylcholine induced relaxation in all vessel segments with intact intima, whereas no relaxation was seen when the endothelium was manually removed. No significant differences were found between the grafts and the normal control vessels. Histology of the 60-day grafts showed elastomuscular arteries without intimal thickening and a media consisting of eight to ten muscle layers interrupted by five to six elastic lamellae. Scanning electron microscopy showed no major differences between normal endothelium and the endothelium of 3-day or 60-day grafts. This study indicates that free elastomuscular arterial grafts, in which the morphology of the intima is preserved, will retain their full ability to release EDRFs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Serum levels of growth hormone-binding protein and insulin-like growth factor-I during puberty.

OBJECTIVE: The aim was to investigate the effect of pubertal development on serum levels of growth hormone binding protein (GHBP) and IGF-I, and to study the relationship between GHBP levels and height standard deviation score (SDS), nutritional state and IGF-I levels. DESIGN AND PATIENTS: The investigation was performed on serum samples from 72 healthy adolescents of different pubertal stage. Results were compared to those obtained in 46 prepubertal children. MEASUREMENTS: Serum levels of GHBP were measured by HPLC gel filtration and IGF-I levels were measured by RIA after acid-ethanol extraction. RESULTS: No effect of pubertal stage on serum levels of GHBP was found. A positive relationship was found between serum levels of GHBP and height SDS (r = 0.38; P < 0.005) and weight expressed as percentage of median weight for height age (r = 0.46; P < 0.0005). Serum levels of IGF-I increased during puberty and were not correlated with height SDS or weight for height age. In pubertal subjects, no relationship existed between serum levels of GHBP and IGF-I. In prepubertal subjects, however, a significantly positive relationship between GHBP and IGF-I levels (r = 0.66; P < 0.0005) was found. CONCLUSIONS: Pubertal development does not seem to influence serum levels of GHBP. Height SDS and nutritional state are related to the concentration of GHBP. Before puberty, the level of GHBP is positively related to IGF-I levels; during puberty, however, the increase in serum IGF-I levels is not accompanied by changes in the amount of circulating GHBP.

Adolescent↗

Hyperthyroidism accelerates growth in Turner's syndrome.

Graves' disease in a girl with Turner's syndrome (karyotype 46,Xdel(Xp)) is described. Hyperthyroidism led to a pronounced acceleration of height velocity. During treatment with methimazole and L-thyroxine, height velocity normalized. The patient also developed spontaneous puberty with a clear-cut pubertal growth spurt. Final height, however, did not appear to be influenced either by Graves' disease or by spontaneous puberty.

Child↗

Serum levels of immunoreactive inhibin, FSH, and LH in human infants at preterm and term birth.

Serum levels of immunoreactive inhibin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined in 112 fetal cord blood samples obtained at birth between 26 and 40 weeks of gestation. High levels of inhibin immunoreactivity were detected in all samples. Between the gestational age of 26 and 28 weeks, the levels (mean +/- SE) were higher (p less than 0.05) in male (21.6 +/- 1.0 U/ml; n = 12) than in female (12.8 +/- 0.2 U/ml; n = 12) fetuses. With ongoing gestation, the serum inhibin immunoreactivity decreased and was found to be similar in male (12.1 +/- 0.3 U/ml; n = 13) and female (9.1 +/- 0.7 U/ml; n = 8) fetuses at term. Serum FSH and LH levels were elevated at the beginning of the 3rd trimester of pregnancy and decreased with ongoing gestation to undetectable values at term birth. Between 26 and 32 weeks of gestation, the FSH levels were higher in females (p less than 0.02), whereas the LH levels were higher in males (p less than 0.01). These observations suggest that in the human fetus the pituitary-gonadal axis is active and presents sexual dimorphism; both characteristics are pronounced early during the 3rd trimester of gestation and decrease towards term.

Female↗

Serum growth hormone-binding proteins in the human fetus and infant.

Growth hormone-binding protein (GH-BP) levels were studied in cord serum of 69 human infants born after 24 to 41 wk of gestation and in serum of 14 infants aged 1 to 3 mo. GH-BP levels were measured by HPLC-gel filtration of serum incubated overnight with 125I-hGH. The radioactive elution profile revealed two small 125I-hGH peaks of high molecular weight and a large peak, corresponding to monomeric 125I-hGH. The first peak of high molecular weight was variable, showed some of the characteristics (high molecular weight, displaceability by a large excess of unlabeled hGH) of the described low affinity, high capacity GH-BP, and did not correlate with gestational age or birth weight (peak I-BP). The second peak was identified as 125I-hGH bound to the high affinity, low capacity GH-BP (peak II-BP). Mean +/- SD specific binding of 125I-hGH to this peak was significantly (p less than 0.0001) different between preterm infants (3.1 +/- 1.1%; n = 51), term infants at birth (4.2 +/ 1.1%; n = 18), and 1- to 3-mo-old infants (8.5 +/- 1.6%; n = 14). To evaluate the effect of intrauterine nutritional state, the ponderal index (weight/lengths) was calculated. Peak II-BP levels were lower (p less than 0.05) in infants with the ponderal index less than 2.35 (2.8 +/- 1.0%; n = 20) than in those with the ponderal index between 2.35 and 2.65 (3.4 +/- 1.2%; n = 29) or greater than 2.65 (3.8 +/- 1.2%; n = 20).(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

Serum growth hormone (GH)-binding protein and insulin-like growth factor-I levels in Turner's syndrome before and during treatment with recombinant human GH and ethinyl estradiol.

Serum levels of GH-binding protein (GH-BP) and insulin-like growth factor-I (IGF-I) were measured in 14 adolescent girls with Turner's syndrome (TS) before and during treatment with recombinant human GH (rhGH) and oral ethinyl estradiol (EE2). Before treatment, the mean +/- SE GH-BP level in TS patients was 33.2 +/- 2.0%; this was higher (P < 0.05) than that in bone age-matched (27.9 +/- 1.1%; n = 13) or chronological age-matched (28.1 +/- 0.8%; n = 17) control girls. The mean +/- SE IGF-I level in TS girls (283 +/- 26 micrograms/L) was comparable to that in bone age-matched controls (255 +/- 17 micrograms/L), but lower (P < 0.005) than that in chronological age-matched pubertal controls (568 +/- 35 micrograms/L). In 7 TS girls treated with daily sc injections of rhGH in a dose of 0.8 U/kg.week for 18 months, serum levels of IGF-I increased from 330 +/- 39 to 707 +/- 48 micrograms/L after 3 months of treatment and remained elevated for the entire observation period (P < 0.002). In contrast, GH-BP levels did not change significantly. In 7 other TS girls, puberty was induced after 2 yr of daily sc injections with rhGH (1 U/kg.week) by adding 100 ng/kg.day EE2, orally, during ongoing rhGH therapy. During 18 months of pubertal induction, serum GH-BP levels increased gradually from 31.4 +/- 2.7% at the start of EE2 treatment to a maximum of 49.2 +/- 0.8% after 1 yr (P < 0.001). Serum IGF-I levels, in contrast, did not change significantly. These results show that in adolescent TS patients 1) pretreatment serum GH-BP levels are higher than in bone age-matched or chronological age-matched control girls, and IGF-I levels are similar to those in bone age-matched but lower than those in chronological age-matched controls; 2) during rhGH treatment GH-BP levels do not change, whereas IGF-I levels increase significantly; and 3) oral EE2 treatment during ongoing rhGH treatment increases GH-BP levels markedly, but does not modify IGF-I levels.

Adolescent↗

Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests.

Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 micrograms/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean +/- SD) increased significantly (P less than 0.001) from 3.7 +/- 1.8 cm/year to 7.6 +/- 1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing.

Adolescent↗

Might free arterial grafts fail due to spasm?

The rat femoral artery was used as a free graft and was studied after 2, 7, 14, 30, and 60 days. The patency of the grafts was 100% (2 days, n = 6), 78% (7 days, n = 9), 63% (14 days, n = 8), 33% (30 days, n = 12), and 18% (60 days, n = 11). Histology showed an intimal thickening after 14 days and the media, which in the controls consisted of eight to ten layers of myocytes, was reduced to six to eight cell layers. During the first 2 weeks the graft segments had an impaired contraction when exposed to Krebs solution with 124 mmol/L K+, whereas after 1 month and later the graft segments approached the controls or had even higher contractile force. The thromboxane mimic U-46619 elicited full contractile force at all times whereas the potency was significantly lower during the first 14 days. Noradrenaline was unable to induce contraction in the graft segments during the first 14 days, but at 30 and 60 days it had regained full contractile force and was significantly more potent (approximately 60 times) in the graft segments compared with the controls. This study suggests that intimal thickening and hypercontractility might be a problem in free muscular arterial grafts.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

High potassium contents in organ preservation solutions cause strong pulmonary vasocontraction.

Euro-Collins (ECS) and UCLA-formula organ preservation solutions induced strong vasocontraction in porcine pulmonary arteries when studied in organ baths at temperatures of 37 degrees C and 30 degrees C. At 20 degrees C ECS induced a 30% contraction, but at 6 degrees C no contraction (n = 5) or a weak contraction (n = 1) was elicited. Neither prostaglandin E1 nor nifedipine caused any significant reduction of the vasocontraction elicited by ECS and UCLA. Krebs solution, enriched with potassium in amounts corresponding to those in ECS (115 mmol/L) or UCLA (30 mmol/L), induced vasocontraction comparing well with those induced by ECS or UCLA, indicating that it is the high potassium content that causes the vasocontraction. In a second experiment lung segments were stored at 4 degrees C for 9 hours in ECS, UCLA, or Krebs solution. Pulmonary arterial segments were then studied in organ baths at 37 degrees C. The choice of preservation solution did not significantly affect the contractile properties of potassium, noradrenaline, or the thromboxane mimic U-46619. To conclude, high potassium contents in organ preservation solutions induce strong pulmonary vasocontraction in lung temperatures greater than 20 degrees C but not in temperatures less than 10 degrees C. These vasocontractions are not significantly reduced by prostaglandin E1 or nifedipine. We suggest that the initial preservation solution used to cool down the lungs should contain 4 mmol/L or no potassium. When the lung temperature is less than 10 degrees C, a second perfusion might be done, and then a high potassium content (if thought to be essential) will not cause vasocontraction.

Alprostadil↗

Effect of growth hormone therapy on thyroid status of girls with Turner's syndrome.

The effect of recombinant human growth hormone (rhGH) administration on thyroid function was studied in 14 girls with Turner's syndrome for 18 months. All patients were euthyroid and had no documented GH deficiency. Treatment with rhGH, administered as daily subcutaneous injections in a dose of 0.15 IU/kg/day, led to a decrease of serum T4 levels from 124 +/- 4 (mean +/- SEM) to 106 +/- 4 nmol/l (P less than 0.05) after 6 months of therapy. Thereafter serum T4 levels returned progressively to baseline levels. Serum TBG levels increased consistently from 21.9 +/- 0.5 to 24.4 +/- 0.9 mg/l (P less than 0.05) after 3 months. Serum T3 and TSH levels did not change significantly during rhGH administration. The T3/T4 ratio (x 100) increased from 1.9 +/- 0.1 to 2.2 +/- 0.1 (P less than 0.05) after 6 months of treatment and returned thereafter to baseline levels. The observed changes in T3/T4 ratio demonstrated a striking parallelism with the changes in height velocity and plasma IGF-I levels. We conclude that rhGH treatment results in a transient alteration of the thyroid status in girls with Turner's syndrome. The functional importance of this phenomenon, in particular its role in the concomitant growth acceleration, remains to be established.

Adolescent↗