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Biomedical subjects

R Rappaport

Publications and source records attributed to R Rappaport.

At least 73 records · Page 4Linked to original sources
PubMed1990

Deglycosylation increases the fibrinolytic activity of a deletion mutant of tissue-type plasminogen activator.

delta 2-89 t-PA is a deletion mutant lacking the finger (F) and epidermal growth factor (EGF) domains; thus, the fibrin interaction of this molecule must be mediated solely by the kringle region. In the present study, the influence of the oligosaccharide side-chains on the activity of delta 2-89 t-PA has been investigated. delta 2-89 t-PA was secreted in two forms, designated I and II, which presumably differ by the lack of one asparagine-linked oligosaccharide in the kringle 2 domain of form II. Forms I and II of delta 2-89 t-PA were purified; form II displayed higher fibrinolytic activity than form I. When form I was partially deglycosylated or treated to remove sialic acid, fibrinolytic activity was increased. Production of delta 2-89 t-PA in the presence of tunicamycin led to secretion of a glycan-free activator with higher activity. These findings suggest that certain oligosaccharide side-chains, particularly those containing sialic acid, can interfere with the interaction between the kringle region of t-PA and fibrin.

Amides↗
PubMed1990

Growth and endocrine disorders in optic glioma.

Hypothalamo-pituitary function in children with optic glioma may be impaired by the tumour itself and by the high cranial radiation doses used in treatment. This study evaluates the effect of optic glioma and its treatment on patient growth and pubertal development. Twenty-one patients (13 boys, 8 girls), treated for optic glioma by cranial irradiation (45-55 Grays) at a mean age of 5.4 years, were evaluated before (n = 10) and/or after (n = 21) irradiation. Growth hormone (GH) deficiency was present in only 1 patient tested before irradiation and in all patients after irradiation. Precocious puberty occurred in 7/21 cases, before irradiation in 5 patients and after irradiation in 2 patients. The cumulative height loss during the 2 years after irradiation was 0.2 +/- 0.2 SD (m +/- SEM) in 7 patients with precocious puberty and 1.1 +/- 0.2 SD in 14 prepubertal patients (P less than 0.01). The corresponding bone age advance over chronological age, evaluated 1-3 years after irradiation, was 1.1 +/- 0.5 and -0.7 +/- 0.3 year in the two groups (P less than 0.01). The mean height loss between time of irradiation and the final height was 2.3 +/- 0.6 SD (n = 6). Primary amenorrhoea, associated with low oestradiol levels, occurred in two of the three girls of pubertal age. These data indicate that the high dose of cranial radiation used to treat optic glioma invariably results in GH deficiency within 2 years and that hGH therapy is required when GH deficiency is documented.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1990

Inhibition of the activity of human leukocyte elastase by lipids particularly oleic acid and retinoic acid.

The effect of various natural hydrophobic lipids on the in vitro and in vivo activity of human leukocyte elastase has been examined. In vitro studies using 2 different substrates indicated that fatty acids inhibit human leukocyte elastase activity, with maximum inhibition observed with oleic acid. Triolein, cholesterol, and beta-carotene caused little inhibition. The presence of a carboxyl group appears important since retinoic acid but not retinol also inhibited activity. In vivo studies of an emphysema model in mice indicated that intrapulmonary instillation of oleic or retinoic acid reduced lung injury caused by human leukocyte elastase. The possibility of using these compounds to diminish elastolytic damage in emphysema is raised.

Animals↗
PubMed1990

Response to growth hormone treatment and final height after cranial or craniospinal irradiation.

Growth hormone (GH) deficiency (GHD) induced by cranial irradiation has become a frequent indication of hGH substitutive therapy. This study analyses the growth response to hGH therapy and the factors involved in the decrease in growth velocity observed after cranial irradiation. One hundred children (61 boys and 39 girls) given cranial radiation for pathology distant from the hypothalamo-pituitary area were studied. Fifty-six of them received hGH therapy for GHD resulting in decreased growth velocity. The initial annual height gain in the cranial-irradiated group was comparable to that of patients treated for idiopathic GHD; additional spinal irradiation significantly reduced the growth response. Twenty-eight hGH-treated patients reached final heights which were compared to those of 2 untreated irradiated groups, one with GHD (n = 27) and the other with normal GH secretion (n = 17). The height SD score changes observed in hGH therapy were +0.3 in the cranial (n = 10) and -1.2 SD in the craniospinal (n = 18) groups. GH deficiency had contributed to a mean height loss of 1 SD and spinal irradiation to a loss of 1.4 SD. The small effect of hGH therapy on final height is probably linked to the small bone age retardation at onset of hGH therapy and to the fact that irradiated children entered puberty at a younger age in terms of chronological age (10.6 +/- 0.3 yr in girls and 11.0 +/- 0.3 yr in boys) and bone age (9.6 +/- 0.4 yr in girls and 12.6 +/- 0.3 in boys) than the idiopathic GHD patients. These data suggest that the results of hGH therapy in irradiated children might be improved with higher and more fractionated hGH doses and, in some patients, by delaying puberty using luteinizing hormone releasing hormone analogs.

Body Height↗
PubMed1990

Recombinant human growth hormone treatment in short children with chronic renal disease, before transplantation or with functioning renal transplants: an interim report on five European studies.

Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterminal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cm/year to 10.0 cm/year in the first group (the chronic renal failure group), from 2.6 cm/year to 6.2 cm/year in prepubertal children with renal transplants and from 3.8 cm/year to 6.7 cm/year in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some of the children with renal transplants showed a decreased renal function, which in most cases was explained by non-compliance or chronic rejection.

Adolescent↗
PubMed1990

Presentation and management of suprasellar arachnoid cysts. Review of 20 cases.

The clinical presentation and treatment of suprasellar arachnoid cysts remain controversial. The authors review 20 cases treated at their institution and 86 cases from the literature reported in sufficient detail for analysis. The high frequency of endocrinological disorders, which not only persist following treatment but may also develop years later despite the satisfactory decrease in volume of the cyst, are emphasized and documented. The difficulties of management are discussed, including; subfrontal approaches to these cysts; removal and/or marsupialization of the cysts, procedures that are frequently dangerous and ineffective; and ventricular shunting which often leads to a paradoxical increase in the size of the cysts. The authors emphasize the advantages of percutaneous ventriculocystostomy, which is a simple, benign, and efficacious procedure.

Adolescent↗
PubMed1990

[Gonadal function after cancer treatments in childhood].

Treatments given for childhood malignancies can alter gonadal function by several mechanisms: (1) cranial irradiation may cause either gonadotrophin deficiency or premature puberty. (2) Irradiation of the testes can induce germinal epithelium dysfunction even if the dose delivered is very low; Leydig cell failure occurs beyond 5-6 Gy and ovarian insufficiency beyond 6-7 Gy. (3) Chemotherapy is considerably more toxic for the germinal epithelium of the testes than for the ovaries; alkylating agents are especially toxic. Analysis of the consequences of preparation for bone marrow transplantation by chemotherapy or total body irradiation will be required when longer follow-up are available.

Antineoplastic Agents↗
PubMed1989

A model for astral stimulation of cytokinesis in animal cells.

A model is proposed in which stimulation of cortical cytoplasm occurs near the distal ends of astral rays. Levels of stimulation sufficient to cause furrowing occur only in equatorial zones between asters. The model can account for positioning of furrows in very large cells (fertilized eggs of amphibians, birds, and fish) and in cells with several mitotic apparatuses (insects). Finally, the model correctly predicts the positioning and occurrence of furrowing in two experiments in which cellular shape was manipulated into either an hourglass or a cylindrical form before division. These results are consistent with equatorial stimulation theories in which mitotic asters differentially stimulate the future furrow region (equatorial cortex). The results are not consistent with models requiring differential stimulation of nonfurrowing, polar regions of the cell.

Animals↗
PubMed1989

Precocious puberty in girls: early diagnosis of a slowly progressing variant.

An attempt was made to identify the less severe cases of precocious puberty and to describe their natural course. A group of 17 girls with precocious puberty and a bone age advance over chronological age of less than two years (group 1) was compared with a group of 19 patients with severe precocious puberty and bone age advance of two years or more (group 2). Mean (SEM) plasma oestradiol concentrations were 82 (30) pmol/l and 164 (21) pmol/l (p less than 0.05), vaginal maturation indexes were 16 (5) and 41 (4), and plasma somatomedin C concentrations were 1.0 (0.2) U/ml (n = 8) and 2.1 (0.3) U/ml (n = 16) in groups 1 and 2, respectively. The time between onset and diagnosis of secondary sexual characteristics was about one year in both groups. After two years' follow up the untreated patients in group 1 had maintained their predicted final height. These changes were in contrast to those observed at first examination in patients in group 2 who had a mean (SD) predicted final height of -1.3 (0.2) and a mean bone age advance of 3.0 (0.2) years. These data show that bone age advance to chronological age, and plasma somatomedin C concentrations measured at initial evaluation are helpful in identifying less severe and potentially slow progressing forms of central precocious puberty.

Age Determination by Skeleton↗
PubMed1989

Lack of adrenarche in two children with precocious puberty secondary to hypothalamic hamartoma.

Adrenarche, which occurs earlier than gonadarche in normal children, is marked by increases in plasma dehydroepiandrosterone and its sulfate (DHAS). Adrenarche and gonadarche can be dissociated in various situations, e.g. central precocious puberty, indicating that they are controlled by independent mechanisms. This report concerns 2 children with central precocious puberty secondary to hypothalamic hamartoma. Their plasma basal DHAS values, compared to other cases with central precocious puberty not secondary to hamartoma, remained low for chronological age and bone age over a follow-up of 6.3 (case 1) and 9.2 9.2 years (case 2): in case 1 (boy), DHAS was 9 micrograms/dl at chronological age 7.7 and bone age 13 years; in case 2 (girl), DHAS was 11 micrograms/dl for chronological age 10.5 and bone age 13.5 years. GH secretion was normal. Basal plasma cortisol levels as the levels during hypoglycemia and after corticotropin stimulation were all normal. These data suggest that hypothalamic hamartoma may affect the central control of adrenarche. They may also contribute to the diagnosis of hypothalamic hamartoma.

Adrenal Glands↗
PubMed1989

Effect of somatomedin-C/insulin-like growth factor I and growth hormone on cultured growth plate and articular chondrocytes.

To determine whether growth hormone has a direct effect on skeletal tissues not mediated by somatomedins, and to better define the role of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) in skeletal development, bovine growth plate, and rabbit articular and growth plate chondrocytes in primary culture were evaluated under a variety of experimental conditions designed to elicit growth hormone and Sm-C/IGF-I stimulation. Under none of these conditions did bovine growth plate chondrocytes respond to either homologous bovine growth hormone or heterologous hGH. Under the same conditions, these cells were highly responsive to human Sm-C/IGF-I with respect to both [3H]thymidine and [35S]sulfate incorporation, indices of mitotic and differentiated cell functions, respectively. Similarly, both rabbit articular and growth plate chondrocytes showed enhanced incorporation of [3H] thymidine and [35S]sulfate in the presence of Sm-C/IGF-I, but did not respond to either native or recombinant hGH. Cells at different stages of maturation within the bovine growth plate differed in their reaction to Sm-C/IGF-I with proliferative zone cells manifesting a greater response to the peptide than cells of the reserve zone. These results suggest that the action of Sm-C/IGF-I on growth plate and articular chondrocytes is direct and that the effect of GH on these cells is indirect. The data further suggest that within the growth plate, the transition from reserve to proliferative status is associated with an increased Sm-C/IGF-I responsiveness, a change which may contribute to the functional differences in these cells.

Animals↗
PubMed1989

Growth and endocrine disorders secondary to cranial irradiation.

External cranial radiation for the treatment of malignant diseases has become a frequent cause of growth hormone deficiency (GHD). The timing of occurrence and the frequency of GHD were related to the hypothalamic-pituitary radiation dose. Frequency varied from 50% in leukemia (2400 cGy) to 75% in face and neck tumors or medulloblastoma (2500-4500 cGy) and up to 100% in optic glioma (greater than 4500 cGy). The significantly more severe growth deficit in patients with GHD given higher radiation doses suggests different levels of residual GH secretion according to radiation dosage. The minimum harmful radiation dose is probably close to 1800-2000 cGy. Our data show that stimulation tests remain a useful means of defining GHD and predicting growth. A fair agreement between GH secretion and growth was found in most cases, regardless of the radiation dose. The only exception was a group of leukemic children (2400 cGy) who achieved normal prepubertal growth despite a low GH response. The 24-h spontaneous plasma GH profiles and IGF-I measurements may add information if growth is retarded despite a normal GH response. We showed that growth retardation occurring after some schedules of total body irradiation was not due to GH deficiency but rather to radiation-induced skeletal lesions. Early or true precocious puberty, generally associated with GHD, was another cause of height loss. As the role of GH deficiency in the final height reduction was demonstrated in all groups of patients after cranial radiation, we suggest that hGH therapy should be considered in any child with proven GH deficiency and significant growth retardation after such radiation.

Child↗
PubMed1989

No evidence for a defect in growth hormone binding to liver membranes in thalassemia major.

To test the hypothesis of a defect in GH-receptor interaction, which could explain the growth failure of thalassemic children, the binding of [125I]human (h) GH to membrane fractions prepared from liver biopsies was studied. Small amounts of liver were obtained from 6 girls and 11 boys with homozygous beta-thalassemia, aged 3-15 yr, all prepubertal, at the time of splenectomy. Specific binding of [125I]hGH ranged from 0.37-5.11% of the added radioactivity/100 micrograms liver membrane protein, with variations in both receptor number and binding affinity. This 14-fold variation in hGH binding to liver membranes of thalassemic children was comparable to that in membrane fractions of livers obtained from normal donors at the time of liver transplant. The binding of insulin to liver membranes from the thalassemic patients ranged from 9.8-17.9% of the added radioactivity/100 micrograms membrane protein and from 2.8-15.0%/100 micrograms membrane protein in the normal donors. Insulin and GH binding to liver membranes did not vary in a consistent way. A 3-fold difference was found in 5'-nucleotidase activity of the membrane fractions. Histological hepatic modifications were assessed with respect to siderosis and fibrosis. No correlation was found between these parameters and GH binding. These results suggest that possible membrane alterations are not the only reason for the variations in hGH binding. All patients had retarded growth, and all but 2 had low plasma insulin-like growth factor I levels. No relationship was found between the level of GH binding to liver membranes and the growth failure. Thus, a defect in GH binding to liver membranes is probably not the cause of the growth retardation of thalassemic children.

Adolescent↗
PubMed1989

A prospective study of the development of growth hormone deficiency in children given cranial irradiation, and its relation to statural growth.

Although GH deficiency (GHD) is the most frequent hormonal abnormality that occurs after cranial radiation, the natural course of this complication and its relationship to growth in children are not known. Therefore, we undertook a 2-yr prospective study of 16 children, aged 1.7-15 yr at the time of treatment, who received cranial [31-42 Gy (1 Gy = 100 rads)] and spinal radiation for medulloblastoma or ependymoma (group I). Their growth was compared to that of 11 children given similar doses of cranial radiation only (group II). The mean plasma GH response to arginine-insulin test (AITT) was 9.1 +/- 1.5 (+/- SE) micrograms/L in group I and 8.5 +/- 1.8 micrograms/L in group II (P = NS). After 2 yr, 16 of the 27 children had a peak plasma GH value below 8 micrograms/L after AITT, and 10 children had a peak response less than 5 micrograms/L. In addition, in group I, AITT and sleep-related GH secretion were compared; at the 2 yr follow-up only 3 of 13 children had discrepant results. At the 2 yr follow-up children treated by cranial and spinal radiation had a mean height of -1.46 +/- 0.40 SD below the normal mean. In contrast, the children given only cranial radiation had a mean height of -0.15 +/- 0.18 SD; P less than 0.02. Therefore, most of the growth retardation appeared to be due to lack of spinal growth. GHD is thus an early complication of cranial radiation in these children, and no significant growth retardation can be attributed to GHD during the first 2 yr. These data contribute to the organization of follow-up in irradiated children in order to decide when human GH treatment is necessary.

Adolescent↗