Plasma isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in patients with hyperthyroidism.

Isocitrate dehydrogenase (ICDH) may be useful for differentiating centrilobular from periportal necrosis in rats with liver injury. In this study, we assessed the usefulness of ICDH as a marker of centrilobular necrosis in patients with hyperthyroidism. Isocitrate dehydrogenase and alanine aminotransferase (ALT) activities were measured in the plasma of 56 patients with hyperthyroidism, 16 patients with chronic viral hepatitis (CVH), and 17 controls. Isocitrate dehydrogenase levels were higher in patients with hyperthyroidism than in those with CVH or in the controls (p < 0.01 and p < 0.001, respectively), even though ALT levels were higher in patients with CVH than in patients with hyperthyroidism (p < 0.01). Isocitrate dehydrogenase/ALT ratios were also higher in patients with hyperthyroidism than in those with CVH (p < 0.0001). Isocitrate dehydrogenase correlated to ALT levels in patients with hyperthyroidism or CVH (p < 0.05). In a patient with hyperthyroidism, ICDH levels decreased progressively to normal, and the ALT level and thyroid function were normalized. Thus, the plasma ICDH or ICDH/ALT ratio might be useful for differentiating centrilobular from periportal necrosis and for monitoring the degree of hepatic necrosis in patients with hyperthyroidism.

Risk factors for recurrence of primary bile duct stones after endoscopic biliary sphincterotomy.

BACKGROUND: Endoscopic biliary sphincterotomy (EST) is a well-established procedure for bile duct stone extraction. Bile duct stones can be classified as primary or secondary. However, few data are available on the recurrence of primary and secondary bile duct stones after EST. Therefore risk factors for the recurrence of primary bile duct stones after EST were prospectively studied. METHODS: Between 1991 and 1997, 61 patients underwent EST for primary bile duct stones. All met the following criteria: (1) previous cholecystectomy without bile duct exploration, (2) detection of bile duct stones at least 2 years after initial cholecystectomy. Mean follow-up was 2.2 years. Fourteen patients were lost to follow-up. The recurrence of primary bile duct stones was defined as the detection of bile duct stones no sooner than 6 months after complete clearance of primary bile duct stones. RESULTS: The overall recurrence rate of primary bile duct stones was 21% (10 of 47). Two significant risk factors for recurrence were identified by multivariate analysis: (1) patients with a bile duct diameter of 13 mm or greater after stone removal had recurrences more frequently than those with a duct diameter of 13 mm or less, and (2) patients whose papilla was located on the inner rim or deep within a diverticulum, so that the papillary orifice was not visible endoscopically, had more frequent recurrences than patients with a papilla outside the diverticulum, or no peripapillary diverticulum. CONCLUSION: The independent risk factors for recurrence of primary bile duct stones were sustained dilation of the bile duct even after complete removal of stones and location of the papilla on the inner rim or deep within a diverticulum.

A new strategy to predict the neoplastic polyps of the gallbladder based on a scoring system using EUS.

BACKGROUND: A new method to predict neoplastic polyps of the gallbladder using a scoring system based on five endoscopic ultrasonography (EUS) variables is presented. METHODS: EUS data from patients with gallbladder polyps who were to undergo cholecystectomy were used for the construction of an EUS scoring system in polyps between 5 and 15 mm in diameter (reference group). The EUS scoring system developed from those patients was applied to other patients (validation group). RESULTS: In the reference group, size was the most significant predictor of neoplastic polyp. All polyps 5 mm or less in diameter were non-neoplastic and 94% of polyps of greater than 15 mm were neoplastic in the reference group. For polyps between 5 and 15 mm in diameter, the area under the receiver-operating characteristic curves (ROC) plots for the endoscopic scoring system was significantly greater than that under the ROC plots for polyp size alone (p < 0.01). In the validation group, the risk of neoplastic polyp was significantly higher for polyps with a score of 6 or greater compared with those with a score of less than 6 (p < 0.01). CONCLUSIONS: Our data show that a score based on five EUS variables identifies those patients at risk of neoplasia when polyps are between 5 and 15 mm in diameter. (Gastrointest Endosc 2000;52:372-9).

Analysis of expressed sequence tags from Brassica rapa L. ssp. pekinensis.

Non-redundant expressed sequence tags (ESTs) were generated from six different organs at various developmental stages of Chinese cabbage, Brassica rapa L. ssp. pekinensis. Of the 1,295 ESTs, 915 (71%) showed significantly high homology in nucleotide or deduced amino acid sequences with other sequences deposited in databases, while 380 did not show similarity to any sequences. Briefly, 598 ESTs matched with proteins of identified biological function, 177 with hypothetical proteins or non-annotated Arabidopsis genome sequences, and 140 with other ESTs. About 82% of the top-scored matching sequences were from Arabidopsis or Brassica, but overall 558 (43%) ESTs matched with Arabidopsis ESTs at the nucleotide sequence level. This observation strongly supports the idea that gene-expression profiles of Chinese cabbage differ from that of Arabidopsis, despite their genome structures being similar to each other. Moreover, sequence analyses of 21 Brassica ESTs revealed that their primary structure is different from those of corresponding annotated sequences of Arabidopsis genes. Our data suggest that direct prediction of Brassica gene expression pattern based on the information from Arabidopsis genome research has some limitations. Thus, information obtained from the Brassica EST study is useful not only for understanding of unique developmental processes of the plant, but also for the study of Arabidopsis genome structure.

cDNA Subtractive Cloning of Genes Expressed during Early Stage of Appressorium Formation by Magnaporthe grisea.

The conidial germ tube of the fungus Magnaporthe grisea differentiates an infection-specific structure, an appressorium, for penetration into the host plant. Formation of the appressorium is also observed on synthetic solid substrata such as polycarbonate. We found that a plant lectin, concanavalin A, specifically suppressed the appressorium formation without affecting the germling adhesion if it was applied within 2-3 hours after germination. Standing on the result, we constructed a cDNA library that represents the early stage of germ tube development and/or appressorium formation from the 2.5-hour-old germ tubes using a cDNA subtraction strategy by the combination of the biotin labeled driver method and adapter-primed PCR method. Out of 686 colonies of the library, 158 distinct clones' nucleotide sequences were partially analyzed. Some clones' expression patterns were detected by RT-PCR and from those results, our library seemed to well represent the objective developmental stage of M. grisea.

Indoleamine-accumulating cell death and endogenous glial cell reaction induced by 5,7-dihydroxytryptamine in the cat retina.

We investigated the patterns of degenerative changes of indoleamine-accumulating cells (IACs) induced by 5,7-dihydroxytryptamine (5,7-DHT, 100 microg), and the glial reaction to the neurodegenerative changes of IACs in the cat retina by using light-and electron-microscopy. The neurons accumulating 5,7-DHT in the cat retina were a few ganglion cells and displaced amacrine cells located in the ganglion cell layer (GCL), and some amacrine cells in the inner nuclear layer (INL). The cell density (per unit area, 1 mm2) of the 5,7-DHT accumulating cells in the GCL and INL was 910 and 134 cells, respectively. Most 5,7-DHT accumulating cells showed dark degeneration characterized by widening of the cellular organelles at early stage, and by darkening of the cytoplasm at a late stage. In addition, amacrine cells, showing a typical filamentous degeneration, were observed in a few cases. The degenerated neurons were phagocytosed by microglial cells and astrocytes. The immunoreactivity for glial fibrillary acidic protein (GFAP) in Muller cells was increased at early stage, but thereafter abruptly decreased. In a few cases, severe degenerative changes were observed in Miller cells. These results indicate that 5,7-DHT induces severe dark degeneration of IACs, and most degenerated cells could be eliminated by microglial cells and astrocytes in the cat retina.

Cyclic AMP Restores Appressorium Formation Inhibited by Polyamines in Magnaporthe grisea.

ABSTRACT Magnaporthe grisea, the causal agent of rice blast, forms a dome-shaped melanized infection structure, an appressorium, to infect its host. Environmental cues that induce appressorium formation in this fungus include the hydrophobicity and hardness of the contact surface and chemicals produced by the host. An elevated concentration of intracellular cyclic AMP (cAMP) has been implicated in appressorium differentiation in M. grisea. Polyamines (putrescine, spermidine, and sper-mine) are involved in cell growth and differentiation in a wide range of organisms. To understand the role of polyamines in appressorium differentiation in M. grisea, intracellular polyamines were quantified, and the effects of polyamines and polyamine biosynthesis inhibitors on conidial germination and appressorium formation were tested. High levels of polyamines were detected in freshly collected spores, but the levels decreased during conidial germination. Spermidine was found to be the major component. Polyamines and polyamine biosynthesis inhibitors did not affect conidial germination, but polyamines specifically impaired appressorium formation. Furthermore, exogenous addition of cAMP restored appressorium formation inhibited by poly-amines. These results suggest that polyamines may reduce intracellular cAMP levels in M. grisea, leading to the inhibition of appressorium formation.

Immediate and long-term effect of mitral balloon valvotomy on left ventricular volume and systolic function in severe mitral stenosis.

To determine the immediate and long-term effect of mitral balloon valvotomy (MBV) on left ventricular (LV) volume and function, we studied 17 patients (mean age 27 +/- 9 years) with severe mitral stenosis undergoing MBV by cardiac catheterization and angiography before and immediately after MBV and at mean 12 months later. At baseline, LV end-diastolic volume index (EDVI) was reduced. Ten patients had EDVI < or = 55 ml/m2, and four patients (23.5%) had LV ejection fraction < 50%. EDVI increased from 60 +/- 17 ml/m2 to 66 +/- 17 ml/m2 (p < 0.05) immediately after MBV and increased further to 72 +/- 16 ml/m2 (p < 0.05) later. Stroke volume index increased from 34 +/- 10 ml/m2 to 41 +/- 12 ml/m2 (p < 0.05) immediately after MBV and increased further to 50 +/- 11 ml/m2 (p < 0.001) later. LV end diastolic pressure increased from 12 +/- 5 mm HG to 16 +/- 4 mm HG (p < 0.05) immediately after MBV and fell to 13 +/- Hg at follow-up. LV ejection fraction increased from 57 +/- 7% to 62 +/- 6% (p < 0.05) immediately after MBV and 71 +/- 8% later (p < 0.001). Mean systolic ejection rate increased from 82 +/- 35 ml/sec to 101 +/- 48 ml/sec (p < 0.05) immediately after and 165 +/- 81 ml/sec later (p < 0.05). Systemic vascular resistance fell from 1887 +/- 525 dyne/sec/cm-5 to 1280 +/- 231 dyne/sec/cm-5 (p < 0.001) at follow-up. We conclude that the LV end-diastolic volume and systolic function are reduced in patients with mitral stenosis, and the LV end-diastolic volume is increased immediately after MBV and continues to increase at follow-up 12 months later; the LV ejection performance improves after successful MBV because of an increase in end-diastolic LV volume (preload) and reduction of SVR.

Activities of the four optical isomers of 2',3'-dideoxy-3'-thiacytidine (BCH-189) against human immunodeficiency virus type 1 in human lymphocytes.

Four different isomers of 2',3'-dideoxy-3'-thiacytidine [beta-DL-(+-)-BCH-189] were evaluated in primary human lymphocytes infected with human immunodeficiency virus type 1. The beta-L-(-) isomer was the most potent enantiomer, with a median effective concentration of 1.8 nM and no discernible cytotoxicity up to 100 microM. The relative order of potencies for the isomers was beta-L-(-) greater than beta-DL-(+-) racemic greater than beta-D-(+) greater than alpha-L-(+) greater than alpha-D-(-). The beta-L-(-) enantiomer was as potent as 3'-azido-3'-deoxythymidine.

Electron microscopic investigation of the vestibular projection to the cat trochlear nuclei.

Ultrastructural degeneration studies were carried out on the cat trochlear nucleus following lesion of the vestibulo-trochlear pathway in order to characterize the location and type of presynaptic endings involved in this pathway. Four types of boutons are found in the normal trochlear nucleus. Types I and II are large and demonstrate typical en passant profiles with small diameter synaptic vesicles (35 and 40 nm). These terminals are characterized by the absence of neurofilaments in the Type II endings. Types III and IV are smaller boutons, located more axondendritically, and contain larger diameter synaptic vesicles (45 nm). Type V terminals contain large, granulated vesicles and occur only rarely. Following the interruption of the ascending projection from the ipsilateral superior and medial vestibular nuclei by parasagittal medullary lesions, degeneration of Type II boutons was commonly encountered in the ipsilateral trochlear nucleus. Predominantly Type III degeneration was found in the contralateral trochlear nucleus. Electrical stimulation of the vestibular nerve showed that these lesions resulted in (1) a complete loss of inhibition in the ipsilateral trochlear nucleus and (2) a significant (75-90%) reduction in the contralateral excitatory pathway to the trochlear nucleus. Midline sagittal lesions in the floor of the fourth ventricle interrupting the decussating fiber projection from the bilateral medial vestibular nuclei resulted in selective degeneration of only Type III boutons in both trochlear nuclei. We conclude that inhibitory vestibular neurons eminating from the superior vestibular nucleus terminate on trochlear motoneurons with Type II boutons and excitatory vestibular neurons from the contralateral medial vestibular nucleus end on trochlear motoneurons with Type III boutons.