Growth hormone induces insulin resistance in Laron dwarf cells via lactogenic receptors

GH is the hormone primarily responsible for regulating body size within the genetic program. While GH has pleiotropic actions on cellular growth and metabolism, most of its effects are believed to be mediated by a single GH receptor. This receptor is not functional in tissues from patients with Laron dwarfism. We used human T-cell leukemia virus-immortalized T-lymphoblast cell lines from Laron dwarfs and normal individuals to examine the mechanism of GH-induced insulin resistance at the cellular level. GH (5-500 micrograms/L) caused a profound decrease in the sensitivity of normal T-lymphoblasts in response to all insulin concentrations (P < 0.0001 vs. insulin alone); pretreatment with GH and GH receptor antibody significantly improved sensitivity to all concentrations of insulin (P = NS vs. insulin alone). Preincubation with GH and PRL receptor antibody was associated with partial improvement in insulin sensitivity (P = 0.004 vs. insulin alone). Thus, in normal T-cell lines, the major pathway of GH-induced insulin resistance appears to be directed by the GH receptor, with a smaller effect mediated through the PRL receptor. While T-cell lines from Laron dwarfs do not respond to GH in clonal proliferation assays, GH (50 and 100 micrograms/L) caused profound insulin resistance in these cells (P = 0.008 and P < 0.0001, respectively, vs. insulin alone). GH receptor antibody did not abrogate this effect at any insulin concentration (P = NS vs. insulin alone), but there was partial restoration of insulin sensitivity when GH and PRL receptor antibody were coincubated (P = 0.0069 vs. insulin alone). Thus, in Laron T-cell lines, PRL and perhaps other lactogenic receptors appear to mediate GH-induced insulin resistance. The kinetics of GH-induced insulin resistance in Laron T-cells were also distinct from the pattern seen in normal T-cells, and unlike in normal cells, GH had no effect on insulin-like growth factor-I-induced clonal expansion of Laron T-cell lines (P = NS vs. insulin-like growth factor-I alone). These results provide evidence for an alternative pathway of GH action revealed in cells lacking classical growth responses to GH.     

Accelerated myelopoietic recovery in irradiated mice treated with Photofrin

Spatial autocorrelation analysis performed on published data pertaining to caste and tribal populations of the Indian subcontinent has revealed that the surfaces of A, B and O allele frequencies are highly fractured. The only significant spatial autocorrelation was observed in respect of the A allele frequency among caste populations.     

cDNA expression studies of rat liver aryl sulphotransferase

A cDNA encoding an isoenzyme of rat liver aryl sulphotransferase was isolated from a rat liver bacteriophage Lambda gt 11 library by the polymerase chain reaction technique. The resulting cDNA was functionally expressed in COS-7 cells and characterised by determining the sulphating capacity of the cells with a range of substrates. The COS-expressed enzyme catalysed the sulphation of both phenol and dopamine with Kms of the same order as those obtained for the high affinity isozyme in rat liver cytosol, while low activity was observed with tyrosine methyl ester. The common food additive vanillin was also a good substrate for sulphate conjugation. The sulphation of vanillin catalysed by the COS-expressed enzyme was consistent with a single enzyme system, in contrast, the kinetics of the reaction catalysed by cytosolic sulphotransferase indicated that vanillin was sulphated by more than one isozyme.     

Psychosocial status of children with diabetes in the first 2 years after diagnosis

OBJECTIVE: The purpose of this study was to determine the pattern of adjustment over time of a cohort of children with newly diagnosed diabetes compared with a cohort of peer-selected children without diabetes over the first 2 years after the diagnosis of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Children (n = 89 with IDDM, n = 53 without IDDM) ages 8-14 years were studied with the Children's Depression Inventory, State-Trait Anxiety Inventory for Children, Child and Adolescent Adjustment Profile, Self-Perception Profile for Children, and a general health scale. Initial data were collected within 6 weeks of the diagnosis of IDDM and at 3, 6, 12, and 24 months thereafter. RESULTS: There were no demographic differences between the two groups. Initially, children with diabetes were more depressed, more dependent, and more withdrawn than their peers. By 1 year postdiagnosis, there were no significant differences in psychosocial status between the two groups. By 2 years postdiagnosis, depression, dependency, and withdrawal were significantly higher in children with diabetes than in their peers without IDDM. Self-perceived competence remained similar between the two groups at all time points. CONCLUSIONS: After an initial period of adjustment, children with IDDM have equivalent psychosocial status to children without IDDM, but by 2 years after diagnosis, they have experienced twice the amount of depression and adjustment problems as their peers. Interventions should be aimed at this critical period between 1 and 2 years postdiagnosis.     

Endometrial thickness: individual and mean growth profiles for different hormone replacement regimens

Currently, there is a paucity of data describing endometrial growth, with most studies concentrating on endometrial thickness immediately prior to implantation or embryo transfer. This study looked at the individual and combined growth profiles of 67 volunteers receiving three different hormone replacement regimens. Each treatment regimen was in excess of that considered necessary for optimal growth, and all promoted an endometrial thickness that would be considered satisfactory for embryo transfer. Three patterns of growth were identified, but overall there was a decrease in the rate of endometrial growth with duration of treatment. As expected, analysis of variance did not show a significant difference between the mean growth profiles for the three hormone replacement regimens. The correlation (r = 0.45, P < 0.0001) between rank order on day 3 and day 10 of treatment indicates that interim analysis during early treatment cannot accurately predict later thickness, but a doubling of endometrial thickness can be expected in most cases. A relationship between endometrial thickness and either the treatment dose or serum concentrations of oestradiol was not found. These findings suggest that manipulation of endometrial growth is not possible by adjustment of either the treatment dose or serum concentration. The findings indicate that treatment beyond 12 days does not promote either a clinically significant increase in endometrial thickness of an excessive thickness, suggesting that maintenance of an oocyte recipient in a pseudo-follicular phase is unlikely to be disadvantageous to implantation.     

Computer-assisted primary screening of cervical smears using the PAPNET method: comparison with conventional screening and evaluation of the role of the cytologist

The reactions of 221 women to their place of delivery (state or private hospital), type of delivery (vaginal or Caesarean) and associated obstetrical interventions were explored by means of a structured interview conducted at 3 months postpartum. Women were randomly selected from the birth records of three cultural groups residing in the municiple area of Johannesburg, South Africa: White (n = 72), Indian (n = 79) and Mixed cultural origin (n = 78). The type of birth experienced by women differed in the cultural groups examined. While most women experienced positive emotional reactions to birth many also expressed a variety of negative reactions. The differences in care experienced by women in the present study reflect the impact of the two systems of care, private and state, that are available to women in South Africa.     

Coronary sinus pacing prevents induction of atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is due to reentry, and its incidence has been shown to decrease after dual-site atrial or biatrial pacing. We investigated whether a simpler pacing approach via the distal coronary sinus (CSd) could eliminate AF inducibility by high right atrial (HRA) extrastimuli (APDs). We based our hypothesis on our previous observation that AF inducibility by HRA APDs was associated with conduction delays to the posterior triangle of Koch, whereas AF was never induced with CSd APDs, which were associated with minimal intra-atrial conduction delays. METHODS AND RESULTS: Programmed electrical stimulation was performed from the high right atrium and CSd, and bipolar recordings were obtained from the high right atrium, His bundle, posterior triangle of Koch, and coronary sinus. In 13 patients (age, 44+/-18 years), AF was reproducibly induced with a critically timed HRA APD (220+/-22 ms) delivered during HRA pacing. AF was not induced in any of the patients when HRA APDs were delivered during CSd pacing at the same critical coupling intervals. Coronary sinus APDs delivered during HRA pacing also were not associated with AF induction. The APD coupling interval measured at the posterior triangle of Koch during CSd pacing was significantly prolonged compared with the one measured during HRA pacing and AF induction (381+/-58 versus 263+/-37 ms; P<.0001). CONCLUSIONS: We propose that CSd pacing suppresses the propensity of HRA APDs to induce AF by limiting their prematurity at the posterior triangle of Koch and not allowing local conduction delay and local reentry to occur.