Cysteinyl leukotrienes in the bile of patients with obstructive jaundice

Background: Cysteinyl leukotrienes (LTs) are potent proinflammatory mediators. They are predominantly excreted from blood by hepatobiliary elimination. To explore the clinical significance of biliary cysteinyl LTs, we determined their concentration changes in bile during treatment in patients with obstructive jaundice. Methods: Bile samples were obtained during endoscopic or transhepatic biliary drainage. Leukotrienes C₄, D₄, and E₄ were quantified by two-step reversed-phase high-performance liquid chromatography and subsequent radioimmunoassay. Results: The increased excretion of cysteinyl LTs (LTC₄ + LTD₄ + LTE₄) decreased between day 1 and 14 after drainage (means, 171 pmol/h to 79 pmol/h; P < 0.02). During drainage, the excretion was higher when there was additional cholangitis (mean, 225 and 86 pmol/h, with and without cholangitis, respectively; P < 0.001). The concentrations of LTD₄ and LTE₄ were also higher with additional cholangitis than without (LTD₄, mean 6.0 vs 2.0 nM; P < 0.05; LTE₄, 6.8 vs 2.4 nM; P < 0.02, respectively). Biliary LTC₄ was detected only in patients with cholangitis. The biliary excretion of cysteinyl LTs was positively correlated with leukocyte concentration (r = 0.68; P < 0.005) and C-reactive protein (r = 0.73; P < 0.005) in blood. Furthermore, only in the absence of cholangitis, the excretion was positively correlated with serum γ-glutamyl transferase (r = 0.76; P < 0.02) and alanine aminotransferase (r = 0.72; P < 0.02). Conclusions: The excretion of biliary cysteinyl LTs increases with the severity of cholestasis and hepatic inflammation in patients with obstructive jaundice. An additional increase of cysteinyl LTs was observed during bacterial cholangitis. The increased biliary excretion of biologically active cysteinyl LTs may contribute to the aggravation of cholestasis and inflammatory reaction in obstructive jaundice. Received: October 1, 2001 / Accepted: March 8, 2002 Acknowledgements. We are indebted to Dr. Gabriele Jedlitschky and Dr. Inka Leier for valuable advice throughout this work. This work was supported by a fellowship awarded to Dr. Masahito Uemura by the Alexander-von-Humboldt Foundation, Bonn, Germany, and in part by the Deutsches Krebsforschungszentrum, Heidelberg, Germany. Reprint requests to: M. Uemura     

Selection and characterization of promoters based on genomic approach for the molecular breeding of oleaginous fungus Mortierella alpina 1S-4

To express a foreign gene effectively, a good expression system is required. In this study, we investigated various promoters as useful tools for gene manipulation in oleaginous fungus Mortierella alpina 1S-4. We selected and cloned the promoter regions of 28 genes in M. alpina 1S-4 on the basis of expression sequence tag abundance data. The activity of each promoter was evaluated using the β-glucuronidase (GUS) reporter gene. Eight of these promoters were shown to enhance GUS expression more efficiently than a histone promoter, which is conventionally used for the gene manipulation in M. alpina. Especially, the predicted protein 3 and the predicted protein 6 promoters demonstrated approximately fivefold higher activity than the histone promoter. The activity of some promoters changed along with the cultivation phase of M. alpina 1S-4. Seven promoters with constitutive or time-dependent, high-level expression activity were selected, and deletion analysis was carried out to determine the promoter regions required to retain activity. This is the first report of comprehensive promoter analysis based on a genomic approach for M. alpina. The promoters described here will be useful tools for gene manipulation in this strain.     

The role of platelet activating factor in ovulation

Ovulation is associated with inflammation-like changes. Platelet activating factor (PAF) participates in the inflammatory process. We evaluated the potential role of PAF in PMSG-HCG induced ovulation with CV3988, a specific PAF receptor antagonist in hyperovulated ICR mice (9-12 weeks old). Furthermore, we investigated whether prostaglandins (PGs) interfered with the ovulation induced by PAF. CV3988 blocked the ovulation in a dose dependent manner, and the significantly reduced ovulatory efficiency was observed at a dose greater than 500 micrograms (p less than 0.001). The ovulatory efficiency reduced by CV3988 (at a dose of 500 micrograms) was recovered by PAF in a dose dependent manner. PGs production in ovary was increased in reversing the blockade of ovulation with CV3988. These results suggest that PAF may be involved in the ovulation process and PGs may not potentiate the ability of PAF to play a role in ovulation.     

Clinical significance of radionuclide studies in the acute phase of myocardial infarction

Tl201 MPS and MGCBS were performed on patients with myocardial infarction in the acute phase and the results were evaluated using a scoring system. The findings obtained in this study can be summarized as follows. There was a significant difference in RNEF between Killip class I and III. Significantly high correlation was noted between RWM score and RNEF. In cases of low RNEF (less than 35%) with poor RWM (less than 7), the incidence of complications, especially malignant PVC (47%, P less than 0.01) was markedly high. There was no obvious correlation between Tl201 MPS and complications. However, adding low RNEF (35% or less) to poor Tl scores (-22 or less) malignant PVC was noted with high frequency. Tl scores on admission were not related to the number of coronary arteries involved. For patients with good Tl score and low RNEF on admission (suspected of having severe ischemia), EF did not necessarily showed a tendency toward improvement. Patients with single-, tow- or three-vessel disease showed no difference in improvement of EF at discharge. There was no marked difference in Tl score on admission among three groups of single lesion of left anterior descending artery; patients with total occlusion without collateral circulation, patients with collateral circulation and patients with recanalization.     

The fibers which leave the Probst's longitudinal bundle seen in the brain of an acallosal mouse: a study with the horseradish peroxidase technique

The congenital absence of the corpus callosum, a brain anomaly frequently noted in humans, has been recently found to occur in some mice of the ddN strain in our laboratory. In the brains of these mice, the Probst's longitudinal bundle is always present on both cerebral hemispheres and gives rise to some aberrant fibers toward the midline. In this research, the neuroanatomical features of these fibers were studied by iontophoretical injections of horseradish peroxidase (HRP) into the neocortex of acallosal mouse brains. The results revealed that the fibers which leave the Probst's longitudinal bundle are, at least, of 3 kinds: namely, the fibers that run out from the anterior portion of the bundle and take a U-turn ipsilaterally without crossing the midline through the septal tissue to go back again into the longitudinal bundle at the level where they have left it; the commissural fibers that leave the bundle from its middle portion and cross through a tiny bridge of tissue associated with the ventral hippocampal commissure to the opposite hemisphere; and the fibers that arise from the posterior portion of the bundle and accumulate as an anomalous fascicle below the cingulum. The observation that no labeled fibers were seen within the anterior commissure in the present HRP materials suggests that the axons from neocortex which are prevented from crossing the midline in mice with congenital absence of the corpus callosum cannot find an alternative pathway via the anterior commissure.     

A histological and histochemical study on glycosaminoglycans in epiphysial cartilage of osteochondrodysplasia rat (OCD/OCD).

The osteochondrodysplasia rat, inherited by a single autosomal recessive lethal gene ocd, shows a typical dwarfing syndrome with systemic subcutaneous edema. The skeletal system is most severely affected. The affected neonates are associated with cleft palate, abnormal kidney position and central nerve system malfunction. The present study describes histological and histochemical appearances of the affected epiphysial cartilage. Irregular columnization, thinner hypertrophic zone, swelled chondrocytes, tightly packed chondrocytes with a poor amount of cartilage matrix was found in the affected. The defining characteristic was a wide-spread degenerating area from the resting to hypertrophic zone. The extracellular matrix (ECM) reacted weakly for the glycosaminoglycans (GAGs). A reduced content of sialic acid in the ECM was suggested. It is concluded that the cartilage abnormalities in the ocd/ocd is a new type disease of osteochondrodysplasia possibly due to some defects in GAGs and/or sialic acid metabolism.     

A consideration through the support to resident diabetic patient and care-giver

Our hospital is a National General Hospital with 585 beds. We began the visiting care service from 1990 and four visiting staffs are working at present. The number of targets was 69 in 2002 including 32 patients over 70 years old and 20 care-givers over 70 years old. Visiting care has been conducted to a 72-year-old female with diabetes since July 2000. The patient is in bedridden condition and at the beginning of visiting, she was taking oral medication but the condition was worsen by poor glycemic control and changed to insulin injection from June 2002 after admission to the hospital repeatedly. The patient undergoes the measurement of blood sugar daily and takes meals with 1,200 to 1,400 kcal prepared by her husband. The care-giver is a 71-year-old husband. He was an "all-work, no-play" type of person and had never done the housework, but he started to manage both housework and nursing because of bedridden of his wife. He is a reticent theorist, hates illogical behavior, and does not swayed by other opinions. He has accepted the things which need new knowledge and techniques such as measurement of blood glucose and insulin injection. However, for meals, he only bought side dishes and placed them. Care such as keeping the patient clean was in a same state. The patient consulted and admission to the hospital repeatedly because conditions were not stable. Visiting nurse supported daily life of patient and care-giver especially in nutrition instruction to continue home life. As the result, attitude and behavior toward nursing of care-giver were changed and the patient could continue home life. Therefore we reported here.     

Urinary disturbance due to HTLV-1 associated myelopathy]

Patients with human T-cell lymphotropic virus type 1 associated myelopathy (HAM) have complaints of urinary disturbance frequently. Symptoms and urodynamic examinations were evaluated in untreated twenty-one patients with HAM. Although two cases (11%) had no urinary symptom, nineteen cases (89%) suffered from dysuria, pollakisuria, incontinence or urgency. The combination of irritative and obstructive urinary disturbance was a characteristic symptom in the HAM patients. In three cases the urinary symptoms preceded the gait disturbance which is a main symptom of HAM. In urodynamic study overactive bladder was found in fourteen cases (66%), although three cases (15%) showed underactive or acontractile bladder with disturbance of urinary sensation. There was no abnormal finding by urethral pressure profile (UPP), but detrusor sphincter dyssynergia (DSD) was revealed frequently by EMG. This typical dysfunction of the HAM patients was thought to be caused by destruction of the lateral column of the spinal cord.