Characterization of a specific somatomedin-c receptor on isolated bovine growth plate chondrocytes.

The interaction of somatomedin (Sm) with growth plate chondrocytes (GPCs) is believed to be the primary stimulus of skeletal growth. Using techniques designed to disrupt as little as possible the phenotypic characteristics of GPCs, we have been able to obtain 3-4 x 10(8) viable cells from the major physes of one newborn calf. The availability of these cells plus essentially pure Sm-C/insulin-like growth factor I, the most GH-dependent Sm, has now made possible detailed studies of the interaction of this radiolabeled peptide with the GPC receptor and of the subsequent processing of this hormone by these cells. The enzymatic methods required to free GPCs from their matrix led to loss of receptors, followed by rapid receptor regeneration by de novo synthesis in suspension cultures. Binding of [125I]iodo-Sm-C to GPCs was time dependent and saturable, with optima at 15 C and pH 7.8. At 37 C, binding peaked at 90 min and declined thereafter. Multiplication-stimulating activity, insulin, and nerve growth factor were less potent than unlabeled Sm-C in competition with [125I]iodo-Sm-C for its receptor. Human GH, epidermal growth factor, and fibroblast growth factor failed to show competition even at 10(-6) M. Analysis of the fate of [125I]iodo-Sm-C bound to GPCs at 37 C provided evidence that this hormone is internalized and extruded from the cell in a partially degraded form. Scatchard analysis of [125I]iodo-Sm-C binding to GPCs and to chondrocytes isolated from articular cartilage revealed similar Ka values, but reproducibly 2-6 times more receptors on growth plate than on articular chondrocytes.

Aberrant puberty.

With the emergence of an understanding of the processes at the cellular level that control the differentiated functions of tissues and eventually manifest as the developmental sequence in the whole animal, it is possible to describe pubertal aberrations in terms that are at once grounded in fundamental concepts of cellular biology and of practical value to the clinician. Delayed puberty and its treatment represent a relatively straightforward problem, submitting to division into two groups of patients: those whose gonadotropin levels are elevated (hypergonadotropic hypogonadism), implying primary gonadal failure; and those whose gonadotropin levels are low (hypogonadotropic hypogonadism), implying either a failure of the central control axis or an adaptive response to a disruptive stress. Precocious puberty is also usefully separable into two distinct groups of patients: those in whom the normal central control axis is activated and those in whom it is not. The workup beyond the basic general stage and the approach to therapy are both determined by into the group into which the patient can be assigned. Advances in imaging technology have enhanced the diagnostic process, and chemical remodeling of the hypothalamic peptide, which mediates control of the pituitary's contribution, has revolutionized the treatment of CMPP, making it imperative that the clinician be able to distinguish those conditions that merit treatment from those that may be observed safely.

Correlation between glycemic control and menstruation in diabetic adolescents.

OBJECTIVE: To determine if a correlation exists between the degree of glycemic control in insulin-dependent diabetic adolescents and menstrual regulation. STUDY DESIGN: A retrospective review of charts of diabetic girls aged 10-18 was performed. Office visits were scheduled every three to six months, at which time pubertal development, menstrual function, growth and diabetic control, including hemoglobin (Hgb) A1C, and complications were assessed. Forty-six patients were eligible for data analysis. Descriptive and inferential statistics, including chi 2 and Student t tests, were applied. RESULTS: Thirty-seven (81%) patients had regular menstrual cycles, and nine (19%) had menstrual disturbances, including secondary amenorrhea (one), oligomenorrhea (seven) and primary amenorrhea followed by oligomenorrhea (one). There were two pregnancies. Six patients used hormonal contraception but none for menstrual regulation. There was a statistically significant difference (P < .05) in mean Hgb A1C concentrations between those with menstrual disturbances (11.4) and those with regular menses (9.7). As Hgb A1C values increased, the percent of patients with menstrual disturbances increased, becoming statistically significant when the Hgb A1C was > 10 (odds ratio 7.3, 95% confidence interval 1.5-35.6). There was no difference (P > .05) between the two groups with respect to age at menarche (156 vs. 152 months), age at onset of diabetes (144 vs. 108 months) and interval between diabetes onset and menarche (54 vs. 41 months). There were no patients in either group with diabetic retinopathy or nephropathy. Four patients were hypertensive, but there was no statistically significant difference (P > .05) between groups. CONCLUSION: Tighter glycemic control, as measured by Hgb A1C concentrations, corresponded to improved menstrual regulation in adolescent insulin-dependent diabetics.

HLA type and the genetic risk for type 1 diabetes mellitus.

One hundred twenty-nine type 1 diabetic children and 176 non-diabetic siblings from the Louisville referral area were HLA typed by microlymphocytotoxicity technique. DR antigen frequencies were compared to frequencies for the Southeast USA population. Frequencies of DR3 and DR4 were significantly increased in both the diabetics and their unaffected siblings relative to the general population and DR2 was decreased. Forty-six percent of diabetic children possessed both DR3 and DR4 antigens while only 7% had neither. The findings are consistent with those in other geographical areas and give strong support to the role of DR3 and DR4 antigens as markers for diabetes susceptibility genes.

Disorders of puberty.

Normal puberty begins between eight and 14 years of age in girls and between nine and 14 years of age in boys. Pubic hair distribution is used to stage puberty, along with breast size and contour in girls and testicular volume in boys. Some children experience constitutional sexual precocity, but precocity is likely to be pathologic if it occurs in very young children, if there is contrasexual development or if the sequence of normal pubertal milestones is disrupted. Delayed puberty may be constitutional, but pathologic causes should be considered. The etiology of a pubertal disorder can often be determined with the use of a focused medical history, a directed physical examination and appropriate diagnostic tests. Treatment for disorders of puberty is determined by the underlying cause.

The impact of cranial irradiation on the growth of children with acute lymphocytic leukemia.

Heights, height velocities, weights, and weight velocities were measured serially in 21 patients with acute lymphocytic leukemia (ALL) who had survived three to five years in continuous complete remission. These patients were assigned randomly to treatment regimens that varied according to whether cranial irradiation was used. Patients receiving cranial irradiation had lower height velocities during therapy than normal subjects and patients not receiving cranial irradiation. Twenty-two other children with ALL, who were irradiated but not randomized, exhibited similar alterations in growth. These results indicate that cranial irradiation, and not leukemia or antileukemia chemotherapy, causes reduced growth.