Atrial natriuretic peptide in human urine

Summary A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4° C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0±1.4 ng/day (mean ± SEM) and the fractional excretion of ANP was 0.7±0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2±29.4 ng/day, which decreased to 53.3±11.0 after successful treatment.Abbreviations ANP atrial natriuretic peptide - hANP human atrial natriuretic peptide - RIA radioimmunoasay - NSB non specific bound - FE_ANP the fractional excretion of atrial natriuretic peptide - FE_Na the fractional excretion of sodium - SIADH the syngrome of inappropriate secretion of antidiuretic hormone     

Expression of insulin-like growth factor 1 receptor in primary breast cancer: immunohistochemical analysis

Insulin-like growth factor-1 receptor (IGF-1R) has been implicated in regulation in tumor growth. The results of previous studies performed by radioimmunoassay are conflicting, and the prognostic significance of IGF-1R expression in primary breast cancer is still controversial. IGF-1R expression was evaluated in formalin-fixed, paraffin-embedded tissue of 210 primary breast cancer patients by using anti-IGF-1R antibody. The clinicopathologic variables and 5-year disease-free survival were studied, and their correlations between IGF-1R expressions were investigated. IGF-1R overexpression was observed in 43.8% of tumors. IGF-1R overexpression had no correlation with prognosis or with other clinicopathologic parameters, such as age, tumor size, nodal status, histologic grade, hormone receptor status, and human epidermal growth factor 2 status. Though its prognostic value in breast cancer is limited, immunohistochemical evaluation of IGF-1R by using this monoclonal antibody may be useful in translational research using archived material.     

Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a neutropenic murine model of trichosporonosis.

We produced disseminated trichosporonosis in a neutropenic murine model with Trichosporon asahii, which was identified by DNA relatedness analysis. We then assessed the efficacy of granulocyte colony-stimulating factor (G-CSF) (30 to 100 microg/kg of body weight per day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.8 to 2 microg/kg x day). The administration of G-CSF either before or after infection improved the survival rate from less than 25% up to 100% (P < 0.05). The effects of G-CSF on organ clearance and histological examinations were most remarkable in the lungs. The levels of tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage fluid (BALF) of neutropenic and G-CSF-pretreated mice were 60 +/- 6 ng/ml and 18 +/- 6 pg/ml, respectively, at 24 h after infection. Immunohistologically, alveolar macrophages proved to be the main source of TNF-alpha in BALF. GM-CSF increased neutrophil counts less significantly than did G-CSF and increased the lethality (P < 0.05) with a high level of TNF-alpha in BALF. Expecting to inhibit TNF-alpha, we administered anti-TNF-alpha intraperitoneally at the dose completely inhibiting TNF-alpha in plasma (2 x 10(4) U), but the TNF-alpha level in BALF and the lethality increased. Though the number of neutrophils at the early stage of infection appeared to be the most critical, the results suggest that other host defense mechanisms, such as TNF-alpha overproduction in the lungs, have an important role in the prognosis of trichosporonosis.     

Isolation of a lactose-binding protein with monocyte/macrophage chemotactic activity. Biological and physicochemical characteristics

BACKGROUND: We established a T cell line, STO-5, which constitutively produced monocyte/macrophage chemotactic activity via human T cell lymphoma-leukemia-virus-induced transformation of normal human T cells. METHODS: We isolated and purified a lactose-binding protein, MCF-pl5-L (MW of about 50 kD, pl of about 5) from a conditioned medium of STO-5. By using highly purified MCF-pl5-L, its biological and physicochemical properties were elucidated in comparison with C5a and MCP-1. RESULTS: MCF-pl5-L exhibited an evident dose-dependent monocyte chemotactic activity (MCA). MCF-pl5-L had no or little affinity for heparin unlike chemokines such as MCP-1. We further found that MCF-pl5-L exhibited potent chemotactic activity not only for monocytes but also for alveolar macrophages. In contrast, C5a and MCP-1 failed to show evident chemotactic activity for alveolar macrophages though they did show MCA. MCF-pl5-L failed to exhibit evident eosinophil and neutrophil chemotactic activities, indicating its chemotactic activity is selective for monocytes/macrophages. Regarding the biological functions of MCF-pl5-L other than MCA and chemotactic activity for alveolar macrophages, we found that MCF-pl5-L but not C5a and MCP-1 could prolong the life span of alveolar macrophages, probably by inhibiting apoptosis of macrophages, and stimulate the production of TNF-alpha from macrophages. CONCLUSIONS: These results suggest that MCF-pl5-L plays a role as an immune modulator for monocytes/macrophages in the site.     

Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12).

Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed.     

Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.     

Genetic Structure of Spatial and Verbal Working Memory

Working memory (WM) encompasses both short-term memory (storage) and executive functions that play an essential role in all forms of cognition. In this study, the genetic structure of storage and executive functions engaged in both a spatial and verbal WM span task is investigated using a twin sample. The sample consists of 143 monozygotic (MZ) and 93 dizygotic (DZ) Japanese twin pairs, ages 16 to 29 years. In 155 (87 MZ, 62 DZ) of these pairs, cognitive ability scores from the Kyodai Japanese IQ test are also obtained. The phenotypic relationship between WM and cognitive ability is confirmed (r = 0.26–0.44). Individual differences in WM storage and executive functions are found to be significantly influenced by genes, with heritability estimates all moderately high (43%–49%), and estimates for cognitive ability comparable to previous studies (65%). A large part of the genetic variance in storage and executive functions in both spatial and verbal modalities is due to a common genetic factor that accounts for 11% to 43% of the variance. In the reduced sample, this common genetic factor accounts for 64% and 26% of the variance in spatial and verbal cognitive ability, respectively. Additional genetic variance in WM (7%–30%) is due to modality specific factors (spatial and verbal) and a storage specific factor that may be particularly important for the verbal modality. None of the variance in cognitive ability is accounted for by the modality and storage genetic factors, suggesting these may be specific to WM.     

Light and electron microscopic analyses of immediate and late tissue damage caused by radiofrequency ablation in porcine liver

Radiofrequency ablation (RFA) is an effective procedure for localized hepatocellular carcinoma. Contrast-enhanced CT depicts the ablated area as a hypoattenuated area without hepatic blood flow; however, light microscopy does not show obvious necrosis in the ablated area. We evaluated liver tissue changes after RFA by light microscopy and electron microscopy. The normal livers of three anesthetized pigs were coagulated using RFA after laparotomy. The liver was examined immediately, and 1 week after operation by light and electron microscopy. After RFA, the liver parenchyma surrounding the needle electrode was brown in color and surrounded by a red marginal zone separate from the normal liver parenchyma. Hematoxylin-eosin staining of the central area did not show cell necrosis, and the structures of liver sinusoids, liver cell cord and the nuclei of hepatocytes were preserved. However, electron microscopic examination of tissue immediately after RFA showed destruction of mitochondria of hepatocytes and fixation of sinusoidal cells. One week later, there was a large quantity of debris in the enlarged sinusoids, in addition to irreversible destruction of hepatocyte organelles. RFA of the porcine liver causes hepatocyte damage. This damage was not evident by light microscopy but clearly identified by electron microscopy.     

Peroxyl radical scavenging capability of fish sauces measured by the chemiluminescence method

Oxygen-related free radicals have been suggested as a cause of aging and various diseases, for example, various cancers and rheumatoid arthritis. A radical scavenger as an antioxidant has been sought in foods. Fish sauces are traditional Asian fermented seasonings. Using the luminol chemiluminescence method, the peroxyl radical scavenging capability of fish sauces was examined. From the IC50 values, many fish sauces have been shown to have a strong scavenging capability as well as soy sauces. A scavenging mechanism is also proposed.