The expression and localization of mRNA for colony-stimulating factor (CSF)-1 in human term placenta.

A 4-kb mRNA for colony-stimulating factor 1 (CSF-1) was detected in normal human placenta at term by Northern blot analysis. In-situ hybridization revealed that the mRNA for CSF-1 was localized in the mesenchymal cells of the chorionic villous stroma, but not in the trophoblasts or capillary epithelial cells. Because there are significant numbers of tissue macrophages (Hofbauer cells) in the placental stroma and because the receptor for CSF-1 (the c-fms proto-oncogene product) is known to be expressed by trophoblasts, our results suggest that CSF-1 produced by placental stromal cells may act as a growth and survival factor for human placental macrophages and trophoblasts.     

Choice of osseous and osteocutaneous flaps for mandibular reconstruction

Microvascular free flap transfer currently represents one of the most popular methods for mandibularreconstruction. With the various free flap options nowavailable, there is a general consensus that no single kindof osseous or osteocutaneous flap can resolve the entire spectrum of mandibular defects. A suitable flap, therefore, should be selected according to the specific type of bone and soft tissue defect. We have developed an algorithm for mandibular reconstruction, in which the bony defect is termed as either “lateral” or “anterior” and the soft-tissue defect is classified as “none,” “skin or mucosal,” or “through-and-through.” For proper flap selection, the bony defect condition should be considered first, followed by the soft-tissue defect condition. When the bony defect is “lateral” and the soft tissue is not defective, the ilium is the best choice. When the bony defect is “lateral” and a small “skin or mucosal” soft-tissue defect is present, the fibula represents the optimal choice. When the bony defect is “lateral” and an extensive “skin or mucosal” or “through-and-through” soft-tissue defect exists, the scapula should be selected. When the bony defect is “anterior,” the fibula should always be selected. However, when an “anterior” bone defect also displays an “extensive” or “through-and-through” soft-tissue defect, the fibula should be usedwith other soft-tissue flaps. Flaps such as a forearm flap, anterior thigh flap, or rectus abdominis musculocutaneous flap are suitable, depending on the size of the soft-tissue defect.     

Influence of the C161T but not Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma on colorectal cancer in an Indian population

The aim of the present study was to investigate associations between Pro12Ala and C161T polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and colorectal cancer (CRC) risk. We recruited 301 newly diagnosed CRC patients and 291 healthy control subjects at the Madras Cancer Institute in Chennai, India, from 1999 to 2001. Genotypes of the Pro12Ala and C161T polymorphisms were determined using the PCR-RFLP method. After adjustment for age, sex, smoking habit, family history and family income, an increased risk of CRC was observed for the C/T + T/T genotype compared to the C/C genotype of the C161T polymorphism (odds ratio = 1.61, 95% confidence interval: 1.10-2.36), whereas no significant association was found for Pro12Ala (odds ratio = 1.06, 95% confidence interval: 0.70-1.61). Analysis with estimated haplotypes showed a significant difference in haplotype frequencies between cases and controls (chi(2) = 11.62, P = 0.009, d.f. = 3). The relationship between the two polymorphisms and CRC risk was not significantly modified by dietary intake of fish. Although the biological mechanisms of the observed association remain to be elucidated, our findings suggest that the C161T polymorphism of the PPAR-gamma gene is related to risk of CRC. Further research is needed to investigate functional implications of polymorphisms of the PPAR-gamma gene in CRC development.     

Opposing effects of isoflurane and sevoflurane on neurogenic pulmonary edema development in an animal model

BACKGROUND: The current study was undertaken to investigate the effects of pretreatment with isoflurane and sevoflurane on the development of neurogenic pulmonary edema in an animal model. METHODS: Rats were exposed to room air (control), 1.5% isoflurane, or 2.5% sevoflurane for 4 h. They were then anesthetized with intraperitoneal injections of pentobarbital sodium, and fibrinogen and thrombin were injected into the cisterna magna to induce neurogenic pulmonary edema. RESULTS: Consecutive injections of fibrinogen and thrombin caused increases in blood pressure, with the peak values obtained in the isoflurane and sevoflurane groups being lower than the control values. The incidence of significant neurogenic pulmonary edema was 58%, 100%, and 8% in the control, isoflurane, and sevoflurane groups, respectively. The lung water ratio, an index of severity of edema, was 4.86 +/- 0.78, 6.15 +/- 0.64, and 4.40 +/- 0.32 in the control, isoflurane, and sevoflurane groups, respectively. Furthermore, immunohistochemical staining for vascular endothelial growth factor demonstrated an increase of expression in the rat lungs exposed to isoflurane. Treatment with an anti-vascular endothelial growth factor antibody during exposure to isoflurane completely inhibited the effect of isoflurane to promote neurogenic pulmonary edema in this model. CONCLUSION: Exposure to 1.5% isoflurane enhances the development of neurogenic pulmonary edema development in this animal model, most likely via release of vascular endothelial growth factor from bronchial epithelial cells, an effect not observed with sevoflurane.     

Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent

Humanin (HN) was originally identified as an endogenous peptide that protects neuronal cells from apoptosis induced by various types of Alzheimers disease-related insults. We have previously indicated that HN increases cellular ATP levels and speculated that this peptide may rescue energy-deficient cells in mitochondrial disorders. Here, we report, for the first time, increased HN expression in skeletal muscles from patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). HN was strongly positive in all ragged-red fibers (RRFs) and some non-RRFs, and most of them were type 1 fibers generally requiring higher energy than type 2 fibers. HN in these fibers was localized in mitochondria. HN expression was also increased in small arteries that strongly reacted for succinate dehydrogenase. Our experiments on muscular TE671 cells indicated the possibility that synthesized HN increases cellular ATP levels by directly acting on mitochondria. From these in vivo and in vitro findings, we propose that HN expression might be induced in response to the energy crisis within affected fibers and vessels in MELAS muscles and further be a possible therapeutic candidate for MELAS.     

Humanin attenuates apoptosis induced by DRPLA proteins with expanded polyglutamine stretches

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal-dominant neurodegenerative disorder caused by expansion of CAG repeats in the DRPLA gene, which codes for a polyglutamine (polyQ) stretch. The expanded polyQs are known to form intracellular aggregates and to confer neurotoxic activity. Recent studies have indicated that activation of apoptosis signal-regulating kinase 1 (ASK1) is involved in polyQ-induced apoptosis. Humanin (HN) is an endogenous peptide that inhibits neuronal cell death caused by mutant Alzheimer’s disease genes, and this neuroprotective factor has recently been reported to suppress apoptosis by inhibiting activation of ASK1. To test the anti-ASK1 effect of HN on polyQ neurotoxicity, we constructed neuronal PC12 cells expressing expanded polyQs under the control of the Tet-Off™ system. Using this cell line, we showed that HN suppresses apoptotic cell death induced by expanded polyQs. However, the suppression was incomplete, suggesting that polyQs also stimulate other pathogenic cascades unrelated to ASK1. We further showed that HN suppresses polyQ aggregate formation. This result implied the possibility that aggregation is also related to the polyQ-mediated cascade involving ASK1 activation. Although the details remain uncertain, our results suggest that ASK1 is potentially involved in pathogenesis of DRPLA and that HN might contribute partially to the suppression of neurodegeneration in polyQ diseases.