Investigation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and mean platelet volume in patients with tinnitus.

OBJECTIVE: This study aimed to evaluate patients with tinnitus in terms of mean platelet volume and platelet distribution width, and to explore neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, recently reported in the literature as being possible inflammation markers. METHODS: This study comprised 64 tinnitus patients and 64 age-matched healthy controls. Statistical significance level was accepted as p < 0.05. RESULTS: Mean platelet volume (t = 3.245, p = 0.002) and platelet distribution width (Z = 3.945, p < 0.001) were significantly higher in the patient group than the control group. CONCLUSION: The results suggest that a prothrombotic condition might play a role in the pathophysiology of tinnitus.

Role of leptin in pregnancy--a review.

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.

Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells.

Leptin is a fat cell-derived hormone that regulates food intake and energy expenditure. We previously demonstrated that leptin is produced by nonadipose cells, i.e. by placental trophoblasts. We also reported that a human trophoblastic cell line, BeWo cells, expresses leptin gene and secretes leptin into culture media. To elucidate the regulatory mechanisms of leptin production by human trophoblasts, we investigated synthesis and secretion of leptin in BeWo cells and in explant cultures of human placental tissue. Leptin production and gene expression in BeWo cells were increased by treatment with forskolin. The forskolin-induced increase in leptin production was completely suppressed by H89, an inhibitor of protein kinase A. Leptin production and gene expression in BeWo cells were increased by treatment with phorbol myristate acetate (PMA). The PMA-induced increase in leptin production was completely suppressed by H7 and staurosporine, both of which are inhibitors of protein kinase C. Leptin secretion from first trimester chorionic tissue was approximately 50-fold greater than that from term placental tissue. Leptin production and gene expression in explant cultures of placental tissue at both stages of pregnancy were augmented markedly by treatment with forskolin or PMA. The present study demonstrated augmentation of leptin production by protein kinase A and protein kinase C in cultured human trophoblasts, thereby leading to a better understanding of the regulatory mechanisms of leptin production in human trophoblasts in vivo.

Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia.

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.

A positive umbilical venous-arterial difference of leptin level and its rapid decline after birth.

OBJECTIVE: We investigated the site of leptin production in the fetoplacental circulation. STUDY DESIGN: We simultaneously determined plasma leptin levels in cord vessels and maternal peripheral veins of 38 healthy pregnant women. We also compared plasma leptin levels in 20 neonates at birth and on the fifth day after birth. RESULTS: Leptin levels in cord vessels were significantly (p < 0.001) lower than those in maternal veins (mean 29.5 ng/ml). Leptin levels in umbilical arteries (mean 9.8 ng/ml) were significantly (p < 0.01) lower than those in umbilical veins (mean 12.9 ng/ml). Leptin levels in neonatal veins on the fifth day (mean 3.0 ng/ml) were markedly (p < 0.001) lower than those in umbilical arteries of the same neonates (mean 10.9 ng/ml). CONCLUSION: The higher leptin levels in umbilical veins than in umbilical arteries and the marked decrease during the neonatal period suggest that the placenta is one of the major sources of leptin in the fetal circulation.

Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans.

Leptin is a circulating hormone that is expressed abundantly and specifically in the adipose tissue. It is involved in the regulation of energy homeostasis, as well as the neuroendocrine and reproductive systems. Here, we demonstrate production of leptin by nonadipose tissue, namely, placental trophoblasts and amnion cells from uteri of pregnant women. We show that pregnant women secrete a considerable amount of leptin from the placenta into the maternal circulation as compared with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was augmented during the course of forskolin-induced differentiation of cytotrophoblasts into syncytiotrophoblasts. Plasma leptin levels were markedly elevated in patients with hydatidiform mole or choriocarcinoma and were reduced after surgical treatment or chemotherapy. Leptin is also produced by primary cultured human amnion cells and is secreted into the amniotic fluid. The present study provides evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.

[A histiocytosis X without histological findings: a new entity of histiocytosis X].

Histiocytosis X is a disorder of the reticuloendothelial system with manifestations usually present in the form of one of three entities, namely; Letterer-Siwe disease, Hand-Schüller-Christian disease and eosinophilic granuloma of the bone. A 32-year-old female was admitted to our hospital in July 1990 because of a bilateral diffuse granular abnormal shadow in the chest. She had a history of bilateral pneumothorax in July 1987. She had been suffering from diabetes insipidus since October 1987, and amenorrhea since January 1989. Miliary tuberculosis, fungus disease, pneumoconiosis, sarcoidosis and collagen disease of the lung were excluded by laboratory examinations, and by observation of the clinical course. Histiocytosis X often combines pneumothorax, diabetes insipidus, amenorrhea and an abnormal radiograph of the chest. We suspected this case was one of Histiocytosis X. But, in her lung biopsy, neither Langerhans cells nor Birbeck granules were found. Furthermore S100 protein immunoperoxidase stain was negative. Therefore, we posit the existence of a new and different subtype of Histiocytosis X without histological findings.

Multiphenotypic lymphoma with rearrangements of the T cell receptor beta chain and gamma chain genes.

A case of chemotherapy-resistant non-Hodgkin's lymphoma simultaneously expressing T cell (CD7)-, B cell (CD19)- and myeloid (CD13, CD33)-associated surface antigens is presented. Cytochemical analysis revealed that the lymphoma cells were positive for terminal deoxynucleotidyl transferase, but negative for myeloperoxidase and esterase. Rearrangements of both the T cell receptor beta chain and gamma chain genes were observed, but the immunoglobulin genes showed a germ line configuration. The rearrangement was not detected within the breakpoint cluster region on chromosome 22. These findings are considered to represent aberrant expressions of the B cell- and myeloid-associated antigens in early-stage T cell lineage lymphoma cells.