Convergence of hepatoportal glucose-sensitive afferent signals to glucose-sensitive units within the nucleus of the solitary tract

Units which are activated by ascending impulses from the liver within the nucleus of the solitary tract (NTS) were identified by electrical stimulation delivered to the hepatic branch of the vagus. Responses of descending units were eliminated by a collision test. The units which showed decreased firing rates during portal infusion of isotonic glucose solution were also glucose-sensitive so that they showed decreased firing rates during topical application of glucose by means of micro-electro-osmotic techniques. It is concluded that glucose-sensitive neurons exist within the NTS and also that they are functionally linked with hepatoportal glucose-sensitive afferent units.     

Observation of cavitation in a mechanical heart valve in a total artificial heart

Recently, cavitation on the surface of mechanical heart valves has been studied as a cause of fractures occurring in implanted mechanical heart valves. The cause of cavitation in mechanical heart valves was investigated using the 25 mm Medtronic Hall valve and the 23 mm Omnicarbon valve. Closing of these valves in the mitral position was simulated in an electrohydraulic totally artificial heart. Tests were conducted under physiologic pressures at heart rates from 60 to 100 beats per minute with cardiac outputs from 4.8 to 7.7 L/min. The disk closing motion was measured by a laser displacement sensor. A high-speed video camera was used to observe the cavitation bubbles in the mechanical heart valves. The maximum closing velocity of the Omnicarbon valve was faster than that of the Medtronic Hall valve. In both valves, the closing velocity of the leaflet, used as the cavitation threshold, was approximately 1.3-1.5 m/s. In the case of the Medtronic Hall valve, cavitation bubbles were generated by the squeeze flow and by the effects of the venturi and the water hammer. With the Omnicarbon valve, the cavitation bubbles were generated by the squeeze flow and the water hammer. The mechanism leading to the development of cavitation bubbles depended on the valve closing velocity and the valve stop geometry. Most of the cavitation bubbles were observed around the valve stop and were generated by the squeeze flow.     

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary antihapten response in mice

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg^-) B cells (centroblasts), and most of their progeny are sIg⁺ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg⁺ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg⁺ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg⁺ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg⁺ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.     

Comparative study on deletions of the dystrophin gene in three Asian populations

The frequency and distribution of deletions of 19 deletion-prone exons clustered in two hot spots in the proximal and central regions of the dystrophin gene were compared in three populations from Singaporean, Japan, and Vietnam. DNA samples obtained from 105 Singaporean, 86 Japanese, and 34 Vietnamese Duchenne muscular dystrophy patients were examined by polymerase chain reaction amplification. Deletions of the examined exons were found in 51.2% of Japanese patients but in 40.0% or less of the Singaporeans and Vietnamese. About two thirds of the deletions were localized in the central region and the remaining deletions were clustered at the proximal region. The most commonly deleted exons at the central deletion hot spot were exon 50 in the Singaporean, exons 49 and 50 in the Japanese, and exon 51 in the Vietnamese population. At the proximal deletion hot spot, the most commonly deleted exons were exons 6 and 8 in the Singaporeans, exons 12 and 17 in the Japanese, and exons 8 and 12 in the Vietnamese. Two cases each from Singapore and Japan had large-scale gross mutations spanning both deletion hot spots. Our results suggest that, although the presence and frequency of the two deletion hot spots may be similar in the three Asian populations analyzed, the distribution and frequency of deletions among the different exons can vary as a result of population-specific intronic sequences that predispose individuals to preferential deletion breakpoints. Received: May 20, 2002 / Accepted: July 1, 2002     

Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ), resulting from down-modulation of Bcl-2 expression

Fas antigen is constitutively expressed in the normal colon epithelium, but considerably diminished in most colorectal carcinomas. In the present study, we examine the relationship between Fas antigen expression and apoptosis using the colorectal carcinoma cell line COLO 201, on which a low grade of Fas antigen is expressed. Anti-Fas antibody had no effect on the induction of apoptosis of COLO 201. However, TNF-α and/or IFN-γ, independently and additively, up-regulated Fas antigen expression on COLO 201 and induced apoptosis in a dose-dependent manner. Both cytokines also increased the COLO 201 sensitivity to anti-Fas antibody, resulting from the down-modulation of Bcl-2 and the up-regulation of Bax. These findings indicate that cytokine(s) plus anti-Fas antibody (which mimics natural Fas ligand) are more effective in inducing apoptosis of COLO 201 than cytokine(s) alone. These findings suggest that immunotherapy in combination with cytokine(s) and lymphokine-activated killer (LAK) cells will become a more effective therapy for cancer than cytokine(s) or LAK cells alone, since the Fas ligand is expressed on activated T cells, natural killer cells and macrophages.     

The effect of a specific thromboxane A2 antagonist, AA-2414 on airway hyperresponsiveness induced by ozone exposure in dogs]

To determine whether thromboxane A2 (TxA2) is involved in airway hyperresponsiveness induced by ozone exposure, we studied the effect of a specific TxA2 antagonist, AA-2414 on ozone-induced airway hyperresponsiveness in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7 Hz oscillation method), and numbers of neutrophils in the peripheral blood, neutrophil counts in bronchoalveolar lavage fluid (BALF), the levels of TxB2 and 6-keto-Prostaglandin F1 alpha (6-keto-PGF1 alpha) in BALF were measured before and after ozone exposure, and after ozone exposure with pretreated AA-2414. Ozone exposure was carried out for 2 hr at an ozone level of 3.06 +/- 0.06 ppm (mean +/- SE). Airway responsiveness to inhaled methacholine increased significantly after ozone exposure (p less than 0.01), and the hyperresponsiveness induced by ozone exposure was inhibited significantly by pretreated AA-2414 (p less than 0.01). Numbers of neutrophils in the peripheral blood and neutrophil counts in BALF increased after ozone exposure, and these increase were not inhibited by pretreated AA-2414. There was no apparent change in the levels of TxB2 in BALF after ozone exposure and after ozone exposure with pretreated AA-2414, however the levels of 6-keto-PGF1 alpha in BALF decreased after ozone exposure and after ozone exposure with pretreated AA-2414 (p less than 0.1). These results suggest that TxA2 plays an important role in the development of airway responsiveness after ozone exposure in dogs, and ozone-induced airway hyperresponsiveness may not be associated with the hyperproduction of TxA2 but with the relative increase of TxA2 due to the decrease of PGI2.     

Functionality of chimeric Rev proteins of HIV/SIV

Studies on functional compatibility of various Rev proteins derived from all known human and simian immunodeficiency virus subgroups have shown that this essential gene product is not always exchangeable among the viruses. In an attempt to map the region of Rev proteins responsible for the observed nonreciprocal complementation, hybrid genomic Rev expression vectors were constructed by exchanging the first and second exons ofrev genes, and were examined for their abilities to activate reporter clones by transfection. With one exception, the second coding exon ofrev gene determined the functional specificity of Rev proteins.     

Dandy-Walker variant in Coffin-Siris syndrome

We describe a five-month-old male infant with Coffin-Siris syndrome, the so-called Dandy-Walker variant (hypoplasia of the cerebellar vermis with cystic dilatation of the fourth ventricle, but without enlargement of the posterior fossa), and partial agenesis of the corpus callosum. Dandy-Walker malformation and mega cisterna magna, but not Dandy-Walker variant, have been reported in Coffin-Siris syndrome. The presence of Dandy-Walker variant in the infant we described confirms that the full continuum of the Dandy-Walker complex can occur in Coffin-Siris syndrome. The yet unidentified gene(s) for the syndrome may be related to the development of the hindbrain.     

The importance of alcohol-induced muscle disease

Alcohol-induced muscle disease (AIMD) is a composite term to describe any muscle pathology (molecular, biochemical, structural or physiological) resulting from either acute or chronic alcohol ingestion or a combination thereof. The chronic form of AIMD is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere affecting more than 2000 subjects per 100,000 population and is thus much more common than hereditary disorders such as Becker or Duchenne muscular dystrophy. Paradoxically, most texts on skeletal myopathies or scientific meetings covering muscle disease have generally ignored chronic alcoholic myopathy. The chronic form of AIMDs affects 40–60% of alcoholics and is more common than other alcohol-induced diseases, for example, cirrhosis (15–20% of chronic alcoholics), peripheral neuropathy (15–20%), intestinal disease (30–50%) or cardiomyopathy (15–35%). In this article, we summarise the pathological features of alcoholic muscle disease, particularly biochemical changes related to protein metabolism and some of the putative underlying mechanisms. However, the intervening steps between the exposure of muscle to ethanol and the initiation of the cascade of responses leading to muscle weakness and loss of muscle bulk remain essentially unknown. We argue that alcoholic myopathy represents: (a) a model system in which both the causal agent and the target organ is known; (b) a myopathy involving free-radical mediated pathology to the whole body which may also target skeletal muscle and (c) a reversible myopathy, unlike many hereditary muscle diseases. A clearer understanding of the mechanisms responsible for alcoholic myopathy is important since some of the underlying pathways may be common to other myopathies. This revised version was published online in July 2006 with corrections to the Cover Date.