Plasma leptin level and its relationship with body composition in hemodialysis patients

Leptin is a newly found hormone secreted by adipocytes that regulates food intake, thermogenesis, and body fat. We measured plasma leptin levels in 103 patients with chronic renal failure treated by hemodialysis and 167 age- and gender-matched healthy control subjects to examine the impact of renal failure on plasma leptin levels and the influence of leptin on body composition measured by dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant decrease in both body fat mass and lean body mass compared with those of the control subjects. Plasma leptin was significantly elevated in the hemodialysis group over the controls. In both groups, leptin was higher in female than male subjects, and it correlated positively with percent body fat. The subjects were divided into six categories according to percent body fat, and plasma leptin levels were compared between the two groups in the same category. Leptin of hemodialysis patients was significantly higher than that of the control subjects in the percent body fat categories of 30 or greater, whereas there was no statistically significant difference in leptin concentrations in the lower percent body fat categories. This was also true in the comparison in each gender, and leptin levels in female subjects showed a more remarkable difference between the hemodialysis and control groups in obese categories. Multiple regression analysis in all subjects indicated that plasma leptin levels were independently affected by percent body fat, plasma insulin concentration, gender, and renal failure. The positive impact of renal failure on leptin remained significant in the subjects with percent body fat of 30 or greater in the multiple regression model, whereas it was no longer significant in the remaining lean subjects. In multiple regression analysis of factors affecting fat mass index and lean mass index, leptin level was selectively associated with fat mass index, but not with lean mass index, regardless of percent body fat ranges. These results indicate that renal failure is an important factor affecting plasma leptin levels, especially in obese female subjects, and that hyperleptinemia was closely related to fat mass but not to lean body mass in hemodialysis patients.     

A case of cystadenocarcinoma of the liver

A case of cystadenocarcinoma of the liver is reported. The patient was a 73-year-old woman in whom a tumor was detected in the lateral segment of the liver during a health examination. Ultrasonograms and computed tomograms showed a multilocular cystic mass. Magnetic resonance imaging (MRI) showed a multilocular lowintensity mass, including a high-intensity portion and a portal branch compressed by the tumor. MRI with gadolinium showed an enhanced cyst wall. The cystic part of the tumor became smaller and the solid part became larger over a 1-month period, indicating that the tumor was malignant. Subsegmentectomy (S₃) was performed and cystadenocarcinoma with cystadenoma was diagnosed by histopathological examination. Identification of changes in the appearance of a tumor should be helpful for the differential diagnosis of cystadenoma and cystadenocarcinoma.     

Some observations on gestational age and birth weight as indicators of risk in newborn infants.

The neonatal mortality rate has so far been used as the most reasonable risk indicator of pregnancy outcomes in a community. This rate, however, has decreased considerably, and a new indicator is required. The proportions of pre-term infants, infants with foetal growth retardation and high-risk infants were defined on the basis of both weight and gestational age at birth. Using these as pregnancy outcome indicators, perinatal risk factors in a rural community were examined. The study results agreed with the general knowledge on perinatal risk factors. This method can be used as an alternative to the conventional method for assessing the maternal and child health in a community.     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effects of salt intake on serum lipoprotein and apolipoprotein metabolism

Recently, food intake in Japan has been characterized by an increase in fat intake, especially animal-fat intake and the maintenance of excess salt (sodium chloride) intake. It is generally accepted that the increase in fat intake is closely related to atherosclerosis, and excess salt intake is a high risk factor for the development of hypertension and cerebrovascular lesions. So far, in almost all reports, the increase in fat intake and excess salt intake have been studied independently, and there have been few reports on the combined effects of these two factors. Taking the above things into consideration, it would seem to be very interesting to investigate the effect of excess salt intake on lipid metabolism. In this paper, we studied the effects of excess salt intake on lipoprotein and apolipoprotein metabolisms, using stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY) as model animals. The results obtained were as follows: A significant increase in the concentration of serum total cholesterol (TC) was observed in SHRSP and WKY, when the rats were given a regular diet (CE-2, Clea Japan Inc.) and 1% sodium chloride solution (1% NaCl) as drinking water for 4 weeks. This was accompanied by a tendency toward increases in the concentrations of serum apolipoproteins in both strains. These results suggest that excess salt intake could accelerate the production of serum total lipoproteins in SHRSP and WKY, when the rats are fed a regular diet. Next, 1% NaCl and a high-fat and high-cholesterol diet (HFC diet) were simultaneously given to SHRSP and WKY for 6 weeks. The effects of simultaneous administration on lipoprotein and apolipoprotein metabolisms were compared with those of HFC feeding. One percent NaCl did not markedly affect hypercholesterolemia in WKY, while it induced more marked hypercholesterolemia in SHRSP that was associated with extreme elevations of serum TC and the atherogenic index (A.I.). This deleterious effect of 1% NaCl in SHRSP was due to drastic elevations of cholesterol contents in the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fractions. This was also associated with marked increases in apo B contents in the VLDL, IDL and LDL fractions and significant increases in apo E contents in the VLDL and IDL fractions. These results indicate that 1% NaCl induced much larger increases in serum atherogenic beta-lipoproteins in SHRSP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.     

A case of constrictive pericarditis due to traumatic pericardial hematoma

Although the cause varies widely, we recently experienced a case of constrictive pericarditis of which cause seemed to be traumatic as described below. The patient was a 62-year-old man having a history of epigastric trauma about 20 years ago. Since then, palpitation appeared and he was recently hospitalized in our department for the purpose of receiving an operation under the diagnosis of constrictive pericarditis. At operation, a hematoma was found in the pericardial region, which was considered to have been caused by trauma in the past. Less reports have so far been available concerning trauma-induced constrictive pericarditis and this case thus seemed to be of rarity as well.     

Enhancement of bradykinin-induced prostacyclin synthesis in porcine aortic endothelial cells by pertussis toxin Possible implication of lipocortin I

Bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells was enhanced by pretreatment of the cells with pertussis toxin or islet-activating protein (IAP) for 5 hr or longer. Although ADP-ribosylation of a protein with a molecular weight of 41–42 kD in the cell membranes was completed by 3 hr after the addition of IAP into the incubation medium, there was good correlation between enhancement of bradykinin-induced prostacyclin synthesis and ADP-ribosylation of the IAP substrate over a wide range of IAP concentrations. Furthermore, even if IAP was removed from the incubation medium at 3 hr, bradykinin-induced prostaglandin synthesis at 24 hr was still potentiated. Cycloheximide and actinomycin D enhanced bradykinin-induced prostacyclin synthesis and apparently blocked the effect of IAP. Since this result suggested the involvement of an inhibitor protein(s) of prostacyclin synthesis in the IAP effect, we studied the effect of IAP on the level of lipocortin I which is known to inhibit phospholipase A₂. Western and Northern blot analyses revealed that IAP decreased the amounts of protein and mRNA of lipocortin I. These results suggest that the enhancement of bradykinin-induced prostacyclin synthesis by IAP is associated with a decrease in the level of lipocortin I.     

Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles.

To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner-city hospitals.     

The effects of prenatal protein-energy malnutrition on ossification of fetal rat bones: a biochemical study

In fetal rats whose dams were fed a low-protein diet, 35S sulfate uptake into the growth plate of the long bone and rib was higher than in the control group. The elution pattern of guanidine-HCl extract in gel chromatography revealed that the malnourished group had more high molecular weight proteoglycans in the dissociative condition and a larger aggregated portion in the associative condition than did the control group; however, the same chondroitin-sulfate chain size existed. Calcium content did not differ in both groups. Aggregated proteoglycan or a high molecular weight proteoglycan that existed in the malnourished group probably played an inhibitory role in calcification. Prenatal protein-energy malnutrition may delay the change of proteoglycan character, which could affect mineralization of fetal bones.