Amged Mustafa

Decreased Plasma Insulin-Like Growth Factor-I Level in Familial Alzheimer’s Disease Patients Carrying the Swedish APP 670/671 Mutation

The plasma insulin-like growth factor I (IGF-I) level was determined in family members carrying the Swedish amyloid precursor protein (APP) 670/671 mutation with or without Alzheimer’s disease (AD) and in age-matched controls from the same family. Plasma growth hormone (GH) and prolactin (PRL) levels were also determined. Measurement of the plasma IGF-I level by radioimmunoassay revealed a significant reduction only in the family members with AD compared to age-matched controls. However, there was no significant difference in the levels of GH and PRL between the mutation carriers with or without AD and their respective age-matched controls. These findings indicate that the mechanism(s) regulating GH and PRL were preserved and those regulating IGF-I levels might be affected in AD patients with the Swedish APP 670/671 mutation.

Muscarinic M3 receptor subtype gene expression in the human heart

Abstract. The heart is an important target organ for cholinergic function. In this study, muscarinic receptor subtype(s) in the human heart were determined using reverse transcription-polymerase chain reaction. Our results demonstrated muscarinic receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts. Receptor autoradiography analysis using selective muscarinic ligands indicated an absence of M1 receptor subtype in the human heart. The level of muscarinic receptor binding in atria was two to three times greater than in ventricles. Our results suggest that muscarinic receptors in the human heart are of the M2 and M3 subtypes. This is the first report of M3 receptors in the human myocardium.

Modulation of Early Immune Responses and Suppression of Trypanosoma brucei brucei Infections by Surgical Denervation of the Spleen

Objective: To examine critical interactions between the nervous system and the immune system during experimental African trypanosomiasis. Methods and Results: Inoculation of Trypanosoma brucei brucei resulted in early interferon (IFN)-γ production, elevated corticosterone and prostaglandin E2 (PGE2) levels and increased splenocyte proliferation, as measured by enzyme-linked immunospot assay, radioimmunoassay and thymidine incorporation assay, respectively. Splenic denervation suppressed IFN-γ, corticosterone and PGE2 production, enhanced splenocyte proliferation, and significantly reduced parasitemia and prolonged rat survival. Conclusions: Our data show substantial effects of the nervous system on early immune responses that may influence the outcome of this disease. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. More investigations are required to understand the evident neural control over the immune system during infectious challenges, which may assist in novel therapeutic approaches.

Reduced levels of insulin-like growth factor-1 receptor (IGF-1R) suppress cellular signaling in experimental autoimmune sialadenitis (EAS).

The nonobese diabetic mouse (NOD) develops destruction and functional impairment of salivary and lachrymal glands, experimental autoimmune sialadenitis (EAS), resembling and representing a model for Sjögrens syndrome (SS). To investigate the mechanisms of tissue destruction in EAS, we analyzed a cell survival promoter insulin-like growth factor-1 receptor (IGF-1R) in the submandibular glands of NOD mice with this disease. We also evaluated the expression of a downstream effector of IGF-1R, BAD. Receptor-binding autoradiography revealed that the IGF-1R levels in submandibular glands from young NOD mice were lower than those in adult NOD mice. Immunofluorescence staining demonstrated that BAD expression in the epithelial cells of the submandibular gland was consistently enhanced throughout the course of EAS in NOD mice. These findings suggest that a reduction in the levels of IGF-1R induces a defective glandular homeostasis in the submandibular gland epithelial cells and triggers EAS.

Prolactin, growth hormone, and IGF-1 in ankles and plasma of adjuvant arthritic rats.

In this study we have investigated the levels of prolactin, growth hormone, and insulin-like growth factor-1 in plasma and in tissue extracts of ankle joints of rats with acute or chronic adjuvant arthritis using enzyme immunoassay (EIA) and radioimmunoassay (RIA). We found a stable content of prolactin in plasma of the different groups but a significantly increased concentration of growth hormone was observed in the plasma of the group with chronic arthritis. Moreover, an increased concentration of insulin-like growth factor-1 was noted in the plasma of the acute group. This evidently had returned to normal levels in the chronic group. In contrast, decreased concentrations of prolactin, growth hormone, and insulin-like growth factor-1 were found in tissue extracts of ankle joints of the group with chronic arthritis. The changes in the levels of these hormones in adjuvant arthritis might suggest that they play a role in the pathogenesis of the disease. Understanding the mechanism(s) of hormonal participation in adjuvant arthritis may open new treatment strategies for rheumatoid arthritis and other inflammatory disorders.

Long-term adrenalectomy decreases NMDA receptors in rat hippocampus.

THE effect of long-term adrenalectomy on NMDA receptors in the rat hippocampus was studied. Hippocampal sections of control and adrenalectomized rats were incubated with [3H]MK-801, a radiolabeled non-competitive inhibitor of the NMDA receptor. Analysis by in vitro autoradiography showed a significant decrease in [3 H]MK-801 binding in the dentate gyrus, CA1 and CA4 areas, as well as the temporal cortex. Results of this study suggest that glucocorticoids are vital for the regulation of the NMDA receptors.

Expression of MHC class II, CD4+ and ED1 molecules in association with selective hippocampal neuronal degeneration after long-term adrenalectomy

THE neuroendocrine and the immune systems are interconnected. Monoclonal antibodies against major histocompatibility complex (MHC) class I, class II, CD4, CD8, pan T cells, and macrophages were used for immunostaining brains from adrenalectomized (ADX) and shamoperated rats to investigate the potential involvement of the immune/inflammatory mechanisms in the neurodegeneration of hippocampus after ADX. Our results demonstrate upregulation of MHC class II, CD4 antigens and activated microglial marker-ED1 expression selectively in the hippocampus after ADX. The absence of CD5 reactivity precludes that these activated cells were T lymphocytes. The activated microglial cells may either be instrumental in the hippocampal neuronal loss or activated secondarily to the neuronal degeneration after long-term adrenalectomy.

The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin‐like growth factor‐I levels in the rat femur

Growth hormone (GH) and insulin‐like growth factor‐I (IGF‐I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF‐I by ovarian steroids is well known, however, their effect on local GH and IGF‐I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF‐I levels as well as on bone density in the rat. Nine month‐old rats were ovariectomized (OVX) or sham‐operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17β‐estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF‐I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF‐I levels. Estradiol treatment increased femur GH and IGF‐I levels compared to SHAM rats. Progesterone restored GH and increased IGF‐I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF‐I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone.