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Biomedical subjects

M Anzo

Publications and source records attributed to M Anzo.

13 recordsLinked to original sources

Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer.

Animals↗

Testicular volume in Japanese boys up to the age of 15 years.

UNLABELLED: Previous studies have indicated that Japanese children grow and mature significantly faster than Caucasian children, thus calling for a separate reference standard for each skeletal and sexual maturity index. To establish normal reference values for testicular volume in Japanese boys, we studied from 1985 to 1995, 900 healthy male children of 0 to 15 years of age for medical history, physical examination, height, weight, sitting height, and head circumference measurements, Tanner sex maturity stage, and testicular size. The testicular volume was determined using a Prader orchidometer by the same observer (N.M.). Based on these data, we established the cross-sectional percentile growth curves (90th, 50th, 10th percentiles) for testicular volume of Japanese boys. The testicular volume of 3 ml was attained at 9.3 years of age (90th percentile), 11.0 years of age (50th percentile), and 12.1 years of age (10th percentile), respectively. CONCLUSION: Swelling of the testis in Japanese children begins approximately 1 year earlier than in Swiss children in accordance with the earlier skeletal maturation in Japanese children.

Adolescent↗

Random X-inactivation in a girl with duplication Xp11.21-p21.3: report of a patient and review of the literature.

We describe a 10-month-old girl with abnormal clinical findings and Xp duplication. She showed poor weight gain and developmental retardation, and had several minor anomalies including pigmentary dysplasia (hypomelanosis of Ito). She had a partial short arm duplication in the paternally derived X chromosome, 46,X,dup(X)(p11. 21p21.3), with the normal and duplicated X chromosomes randomly inactivated. These findings indicate that gross functional imbalance in the cells with an active dup(X) chromosome has caused global developmental defects in the patient, and that functional chromosomal mosaicism with respect to the duplicated Xp region has resulted in pigmentary dysplasia. Literature review of 52 patients with partial X duplications revealed (1) random or skewed but not completely selective X-inactivation in 9 of 45 patients examined for the X-inactivation pattern, independently of the size or location of duplicated segments, (2) apparently normal phenotype in 6 of 9 patients with random or skewed X-inactivation, and (3) an abnormal phenotype in 13 of 35 patients with completely selective inactivation of dup(X) chromosomes.

Abnormalities, Multiple↗

Treatment with a gonadotropin-releasing-hormone analog and attainment of full height potential in a male monozygotic twin with gonadotropin-releasing hormone-dependent precocious puberty.

UNLABELLED: We report on a pair of male monozygotic twins, one unaffected and the other affected with gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, and discuss the role of treatment with a GnRH analog in the attainment of full height potential in GnRH-dependent precocious puberty. At 1.6 years of age, the affected twin was studied for tall stature (+3.8 SD), and was diagnosed as having GnRH-dependent precocious puberty due to a hypothalamic hamartoma of the tuber cinereum. He was treated with oral cyproterone acetate (110-170 mg/m(2) daily) from 1.8 through 5. 0 years of age, with oral cyproterone acetate and intranasal buserelin acetate (700-900 microg/m(2) daily) from 5.0 through 7.5 years, and with intranasal buserelin acetate alone (1100- 1400 microg/m(2) daily) from 7.5 through 12.6 years. He attained a final height of 171.0 cm at 14.9 years of age (+0.10 SD) and his twin 170. 0 cm at 15.3 years of age (-0.10 SD), with their target height being 174.5 +/- 9.0 cm. CONCLUSION: This study indicates that GnRH analog treatment may preserve near full height potential in some patients with GnRH-dependent precocious puberty.

Administration, Inhalation↗

A case of congenital hypopituitarism: difficulty in the diagnosis of ACTH deficiency due to high serum cortisol levels from a hypothyroid state.

A three-month-old boy presented congenital hypopituitarism in which the hypothyroid state masked ACTH deficiency. Multiple anterior pituitary hormone deficiencies, including ACTH, were finally confirmed. High basal serum cortisol levels (up to 45.1 microg/dl) were observed during a stressful episode before L-thyroxine replacement therapy was started. Decreased morning serum cortisol levels (5.0 microg/dl or below) were observed on the sixth day of L-thyroxine replacement therapy despite mild hypoglycemia (lowest serum glucose level of 50 mg/dl). ACTH deficiency was then confirmed by insulin-induced hypoglycemia test (peak serum cortisol level of 4.9 microg/dl). The present findings showed that serum cortisol levels can be high during a stressful episode in an infant with ACTH deficiency and a coexisting hypothyroid state. Thus, the diagnostic evaluation of adrenal function soon after L-thyroxine replacement therapy is important in order to verify a possible subclinical ACTH deficiency, even in the presence of high serum cortisol levels before L-thyroxine replacement therapy.

Adrenocorticotropic Hormone↗

Setting up an automated system for evaluation of bone age.

The "Tanner-Whitehouse 2" method is the most popular in evaluating skeletal maturation, but this method has some inherent weak points. We therefore developed the new system to automatically evaluate the skeletal maturation of Japanese children by means of a personal computer. The subjects of this study were 318 healthy Japanese boys and 199 girls ranging from 2 to 15 years of age. The bone age was calculated by multiple regression analysis with parameters for the epiphysis and metaphysis. Successful automatic evaluation was about 80-90% on each phalanx. There was a significant correlation between chronological age and the ratio of epiphyseal width to metaphyseal width. The system developed in this study was useful for evaluating the skeletal maturation.

Adolescent↗

Hepatic dysfunction in two sibs with Alström syndrome: case report and review of the literature.

Alström syndrome is an autosomal recessive disorder (MIM No. *203800) characterized by retinal degeneration, obesity, deafness, noninsulin-dependent diabetes mellitus, and nephropathy. We report two sibs with Alström syndrome and hepatic dysfunction. The first sib developed elevations in liver enzymes at 29 years of age. Liver biopsy showed fatty liver, lymphocytic infiltration, and piecemeal necrosis. The second sib had had elevated gamma-glutamyltransferase levels since she was 10 years old. She developed ascites, esophageal varices, and splenomegaly in her twenties. Cirrhosis was confirmed by autopsy; the patient was 26 years of age at death. Three Alström syndrome patients with hepatic dysfunction have been documented previously. No specific cause was identified for liver disease in any of the patients, including ours. Hepatic dysfunction appears to be a manifestation of Alström syndrome.

Abnormalities, Multiple↗

High ratios of free to total insulin-like growth factor-I in early infancy.

Insulin-like growth factor-I (IGF-I) is a major effector of somatic growth and metabolism. In normal, nonpregnant plasma, most of the IGF-I is complexed to specific IGF-binding proteins (IGFBPs), particularly IGFBP-3; only a minor fraction of plasma IGF-I exists in a free form. Recently, we have reported that free IGF-I levels, as measured using a new immunoradiometric assay, are relatively high in maternal plasma during pregnancy because of increased IGFBP-3 proteolytic activity. These high free IGF-I levels are physiologically important for the growth of maternal tissues such as uterus and placenta, which are related to the fetal growth. Growth during early infancy may be a continuation of fetal growth. In the present study, we have analyzed free and total plasma IGF-I and IGFBP-3 proteolytic activity in early infancy. Although the levels of free and total IGF-I were not significantly different in early infancy as compared with prepubertal periods, the ratio of free to total IGF-I (mean = 2.04%) was relatively increased and was similar to the ratio in pregnancy plasma (1.86%). However, unlike in maternal plasma, the high ratios were not totally caused by increased IGFBP-3 proteolytic activity. Our results suggest that there may be an increased conversion of plasma IGF-I to a free form in early infancy. The resultant increase in IGF-I bioavailability could contribute to the rapid somatic growth in early infancy.

Adult↗

Clinical utility of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 levels in the diagnosis of GH deficiency (GHD) during childhood.

Diagnosis of GH deficiency (GHD) has been done traditionally by the combination of auxological data and the results of GH provocation tests. Recently, limitations of GH provocation tests have been advocated. Thus, three extreme subgroups (G-1; normal, G2; severe GHD, G-3; short children with normal GH secretion) were selected in order to show that insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels reflect GH secretion. In G-1 (n = 52), all had normal IGF parameters. In G-2 (n = 27), all had low IGF parameters. In G-3 (n = 28), all except for one patient had normal IGF parameters. Taken together with the assumption that GH secretion status is continuous from 0 to normal (or to acromegalic), the data on IGF parameters in the three subgroups indicate that they are functional tests for GH secretion. IGF-I and IGFBP-3, together with free IGF-I and acid-labile subunit, may replace GH provocation tests in the diagnosis of GH deficiency during childhood; these functional tests for GH secretion, which show minimal intradaily variation, are more physiological and cost-effective than GH provocation test.

Child↗

Clinical information on serum IGFBP-3 levels and IGFBP-3 proteolytic activity in childhood.

In this review paper, three pieces of clinical information in childhood are presented: (1) IGFBP-3 may replace GH provocation tests in the diagnosis of GH deficiency (GHD); (2) IGFBP-3 levels are regulated by IGF-I levels in a short period, and (3) ratio of free IGF-I to total IGF-I is high in serum of early infancy, similarly to serum of pregnancy, only partially owing to the presence of IGFBP-3 proteolytic activity. Each paper will be published soon.

Adolescent↗

Hyper-IgM immunodeficiency with disseminated cryptococcosis.

We describe two siblings with X-linked hyper-IgM immunodeficiency. One patient developed disseminated cryptococcosis. Co-culture of this patient's T cells with normal B cells suppressed IgG and IgA production. The CD40 ligand gene of one patient was examined and contained a nonsense mutation at nucleotide 475. CD40 ligand is a membrane protein which is expressed on activated T cells and induces B-cell proliferation. These results suggest that there is a defect in T- and B-cell interactions in this immunodeficiency syndrome. It is also possible that patients with this syndrome are predisposed to cryptococcal infections.

Antigens, CD↗

Standard RUS skeletal maturation of Tokyo children.

A total of 704 girls and 753 boys, all healthy, from 3 to 18 years of age, from Tokyo and its suburbs, were radiographed on the left hand and wrist in 1986. Their RUS (TW2) skeletal maturity was estimated, the 50th-centile skeletal maturity scores were obtained, and the smoothed RUS maturity curves were determined applying the cubic spline function to the 50th-centile scores. On this maturity curve the score at each 0.1 year of chronological age was obtained and allocated as a given RUS skeletal age. This set of scores and ages we termed the TW2-J RUS, i.e. the Japanese TW2 RUS maturity standard. Comparing this RUS standard with the British standard, the Belgian, the southern Chinese, and the northern Indian, it became clear that Japanese children's RUS skeletal maturity progresses rapidly during puberty (after ages 9 in girls and 11 in boys), and that the maximum score difference between neighbouring age groups was observed at ages 12.5 in girls and 14.5 in boys on the spline-smoothed curve. Japanese children attain the adult stage 1 or 2 years earlier than other groups of children (at ages 15 in girls and 16 in boys).

Adolescent↗